March advanced organicchemistry reactions mechanisms and structure 2

REACTIONS 973 CO and H2O as a nucleophile is often called Reppe carbonylation.1497 The toxic nature of nickel tetracarbonyl has led to development of other catalysts.1498 Indeed, variations in the reaction procedure include the use of Pd,1499 Pt,1500 and Rh1501 catalysts This reaction converts alkenes, alkynes, and dienes and is tolerant of a wide variety of functional groups When the additive is alcohol or acid, saturated or unsaturated acids, esters, or anhydrides are produced (see Reaction 15-36) The transition metal catalyzed carbonylation has been done enantioselectively, with moderate-to-high optical yields, by the use of an optically active palladium-complex catalyst.1502 Alkenes also react with Fe(CO)5 and CO to give carboxylic acids.1503 Electrochemical carboxylation procedures have been developed, including the conversion of alkenes to 1,4-butanedicarboxylic acids.1504 A reductive carboxylation of alkenes with CO and cesium carbonate has been reported.1505 When applied to triple bonds, hydrocarboxylation gives a,b-unsaturated acids under very mild conditions Triple bonds give unsaturated acids and saturated dicarboxylic acids when treated with CO2 and an electrically reduced Ni complex catalyst.1506 Alkynes also react with NaHFe(CO)4, followed by CuCl2 H2O, to give alkenyl acid derivatives.1507 A related reaction with CO and Pd catalysts in the presence of SnCl2 leads to conjugated acid derivatives.1508 Terminal alkynes react with CO2 and Ni(cod)2 (cod ¼ 1,5-cycloctadiene), and subsequent treatment with DBU gives the a,b-unsaturated carboxylic acid.1509 When acid catalysts are employed, in the absence of nickel carbonyl, the mechanism1510 involves initial attack on a proton, followed by attack by CO on the resulting carbocation to give an acyl cation, and subsequent reaction with water gives the product 107 Markovnikov’s rule is followed, and carbon skeleton rearrangements and double-bond isomerizations (prior to attack by CO) are frequent Á O + H+ H C O H O H2 O OH H 107 Tsuji, J Palladium Reagents and Catalysts Wiley, NY, 1999; Hohn, A in Applied Homogeneous Catalysis with Organometallic Compounds, Vol VCH, NY, 1996, p 137; Beller, M.; Tafesh, A.M in Applied Homogeneous Catalysis with Organometallic Compounds, Vol VCH, NY, 1996, p 187; Drent, E.; Jager, W.W.; Keijsper, J.J.; Niele, F.G.M in Applied Homogeneous Catalysis with Organometallic Compounds, Vol VCH, NY, 1996, p 1119.; Bertoux, F.; Monflier, E.; Castanet, Y.; Mortreux, A J Mol Catal A: Chem 1999, 143, 11; Beller, M.; Cornils, B.; Frohning, C.D.; Kohlpaintner, C.W J Mol Catal A: Chem 1995, 104, 17; Milstein, D Acc Chem Res 1988, 21, 428; Tsuji, J Acc Chem Res 1969, 2, 144; Bird, C.W Chem Rev 1962, 62, 283 1498 For a review, see Kiss, G Chem Rev 2001, 101, 3435 1499 See Heck, R.F Palladium Reagents in Organic Synthesis Academic Press, NY, 1985, pp 381–395; Mukhopadhyay, K.; Sarkar, B.R.; Chaudhari, R.V J Am Chem Soc 2002, 124, 9692; Takaya, J.; Iwasawa, N J Am Chem Soc 2008, 130, 15254 1500 Xu, Q.; Fujiwara, M.; Tanaka, M.; Souma, Y J Org Chem 2000, 65, 8105 1501 Xu, Q.; Nakatani, H.; Souma, Y J Org Chem 2000, 65, 1540 1502 Alper, H.; Hamel, N J Am Chem Soc 1990, 112, 2803 1503 Brunet, J.-J.; Neibecker, D.; Srivastava, R.S Tetrahedron Lett 1993, 34, 2759 1504 Senboku, H.; Komatsu, H.; Fujimura, Y.; Tokuda, M Synlett 2001, 418 1505 Williams, C.M.; Johnson, J.B.; Rovis, T J Am Chem Soc 2008, 130, 14936 1506 Du~ nach, E.; Derien, S.; Perichon, J J Organomet Chem 1989, 364, C33 1507 Periasamy, M.; Radhakrishnan, U.; Rameshkumar, C.; Brunet, J.-J Tetrahedron Lett 1997, 38, 1623 1508 Takeuchi, R.; Sugiura, M J Chem Soc Perkin Trans 1, 1993, 1031 1509 Saito, S.; Nakagawa, S.; Koizumi, T.; Hirayama, K.; Yamamoto, Y J Org Chem 1999, 64, 3975 See also, Takimoto, M.; Shimizu, K.; Mori, M Org Lett 2001, 3, 3345 1510 See Hogeveen, H Adv Phys Org Chem 1973, 10, 29 1497 974 ADDITION TO CARBON–CARBON MULTIPLE BONDS For the transition metal catalyzed reactions, the nickel carbonyl reaction has been well studied and the addition is syn for both alkenes and alkynes.1511 The following is the accepted mechanism:1511 Ni(CO)4 Step + Step Step Step Ni(CO)3 + CO Ni(CO)3 Ni(CO)3 + Ni(CO)3 H H+ Ni(CO)3 H H Ni(CO)3 H Step Ni(CO)2 O H O Ni(CO)2 OH O Step is an electrophilic substitution The principal step of the mechanism, step 4, is a rearrangement An indirect method for hydrocarboxylation involves the reaction of an alkene with a borate [(RO)2BH] and a Rh catalyst Subsequent reaction with LiCHCl2, and then NaClO2, ÀC ! RC(CO2H)CH3.1512 When a chiral gives the Markovnikov carboxylic acid (RCÀ ligand is used, the reaction proceeds with good enantioselectivity 15-36 Carbonylation, Alkoxycarbonylation, and Aminocarbonylation of Double and Triple Bonds Alkyl, Alkoxy, or Amino-carbonyl-addition R—NH2 + O CO, cat H RHN + R—OH H RO O R1 + R1 O CO, cat CO, cat H R1 R1 In the presence of certain metal catalysts, alkenes and alkynes can be carbonylated or converted to give an amide or an ester.1513 There are several variations The reaction of an alkyl iodide and a conjugated ester with CO, (Me3Si)3SiH, and AIBN in supercritical CO2 (Sec 9.D.ii) gave a g-keto ester.1514 Terminal alkynes react with 1511 1512 1513 1514 Bird, C.W.; Cookson, R.C.; Hudec, J.; Williams, R.O J Chem Soc 1963, 410 Chen, A.; Ren, L.; Crudden, C.M.; J Org Chem 1999, 64, 9704 See Fallis, A.G.; Forgione, P Tetrahedron 2001, 57, 5899 Kishimoto, Y.; Ikariya, T J Org Chem 2000, 65, 7656 REACTIONS 975 CO and methanol in the presence of CuCl2 and PdCl2 to give a b-chloroa,b-unsaturated methyl ester.1515 Conjugated dienes react with thiophenol, CO and Pd(OAc)2 to give the b,g-unsaturated thioester.1516 Allene reacts with CO, CH3OH, and a Ru catalyst to give methacrylic acid.1517 Alkynes react with thiophenol and CO with a Pd1518 or Pt1519 catalyst to give a conjugated thioester Terminal alkynes react with CO and CH3OH, using a combination of a palladium(II) halide and a copper(II) ÀCÀÀCO2Me.1520 A similar reaction halide, to give a conjugated diester, MeO2CÀÀCÀ with alkenes using a combination of a Pd and a Mo catalyst led to a saturated diester (MeO2CÀÀCÀÀCÀÀCO2Me).1521 Alkenes were converted to the dimethyl ester of 1,4butanedioic acid derivatives with CO/O2 and a combination of PdCl2 and CuCl catalysts.1522 Note that alkenes primarily are converted to the anti-Markovnikov ester upon treatment with arylmethyl formate esters (ArCH2OCHO) and a Ru catalyst.1523 Terminal alkynes react with tosyl azide, water, and a catalytic amount of CuI to give an N-tosyl amide.1524 A bicyclic ketone was generated when 1,2-diphenylethyne was heated with carbon monoxide, methanol and a dirhodium catalyst.1525 2-Iodostyrene reacted at 100  C with CO and a Pd catalyst to give the bicyclic ketone 1-indanone.1526 Another variation reacted a conjugated allene–alkene with atm of CO and a Rh catalyst to give a bicyclic ketone.1527 An intermolecular version of this reaction is known using a Co catalyst, giving a cyclopentenone1528 in a reaction related to the Pauson–Khand reaction (see below) The reaction of a conjugated diene having a distal alkene unit and CO with a Rh catalyst led to a bicyclic conjugated ketone.1529 When a Stille coupling (Reaction 12-15) is done in a CO atmosphere, conjugated ketones of the 1530 suitable for a Nazarov cyclization (Reaction type CÀ ÀCÀÀCOÀÀCÀ ÀC are formed, 15-20) Alkynes were converted to cyclobutenones using Fe3(CO)12 to form an initial complex, followed by reaction with copper(II) chloride.1531 An interesting variation treated cyclohexene with molar equivalents of Oxone and a RuCl3 catalyst to give 2-hydroxycyclohexanone.1532 Li, J.; Jiang, H.; Feng, A.; Jia, L J Org Chem 1999, 64, 5984 See also, Clarke, M.L Tetrahedron Lett 2004, 45, 4043 1516 Xiao, W.-J.; Alper, H J Org Chem 2001, 66, 6229 1517 Zhou, D.-Y.; Yoneda, E.; Onitsuka, K.; Takahashi, S Chem Commun 2002, 2868 1518 Xiao, W.-J.; Vasapollo, G.; Alper, H J Org Chem 1999, 64, 2080 1519 Kawakami, J.-i.; Mihara, M.; Kamiya, I.; Takeba, M.; Ogawa, A.; Sonoda, N Tetrahedron 2003, 59, 3521 1520 Li, J.; Jiang, H.; Chen, M Synth Commun 2001, 31, 3131; El Ali, B.; Tijani, J.; El-Ghanam, A.; Fettouhi, M Tetrahedron Lett 2001, 42, 1567 1521 Yokota, T.; Sakaguchi, S.; Ishii, Y J Org Chem 2002, 67, 5005 1522 Dai, M.; Wang, C.; Dong, G.; Xiang, J.; Luo, J.; Liang, B.; Chen, J.; Yang, Z Eur J Org Chem 2003, 4346 1523 Ko, S.; Na, Y.; Chang, S J Am Chem Soc 2002, 124, 750 1524 Cho, S.H.; Yoo, E.J.; Bae, I.; Chang, S J Am Chem Soc 2005, 127, 16046 1525 Yoneda, E.; Kaneko, T.; Zhang, S.-W.; Onitsuka, K.; Takahashi, S Tetrahedron Lett 1999, 40, 7811 1526 Gagnier, S.V.; Larock, R.C J Am Chem Soc 2003, 125, 4804 1527 Murakami, M.; Itami, K.; Ito, Y J Am Chem Soc 1999, 121, 4130 1528 Jeong, N.; Hwang, S.H Angew Chem Int Ed 2000, 39, 636 1529 Lee, S.I.; Park, J.H.; Chung, Y.K.; Lee, S.-G J Am Chem Soc 2004, 126, 2714 1530 Mazzola, Jr., R.D.; Giese, S.; Benson, C.L.; West, F.G J Org Chem 2004, 69, 220 1531 Rameshkumar, C.; Periasamy, M Tetrahedron Lett 2000, 41, 2719 1532 Plietker, B J Org Chem 2004, 69, 8287 1515 976 ADDITION TO CARBON–CARBON MULTIPLE BONDS The reaction of dienes, diynes, or enynes with transition metals1533 (usually Co)1534 forms organometallic coordination complexes Rhodium,1535 Ti,1536 Mo,1537 and W1538 complexes have been used for this reaction In the presence of CO, the metal complexes derived primarily from enynes (alkene–alkynes) generate cyclopentenone derivatives in what is known as the Pauson–Khand reaction.1539 This reaction involves (1) formation of a hexacarbonyldicobalt–alkyne complex and (2) decomposition of the complex in the presence of an alkene.1540 A typical example is the preparation of 108.1541 Cyclopentenones can be prepared by an intermolecular reaction of a vinyl silane and an alkyne using CO and a Ru catalyst.1542 Carbonylation of an alkene–diene using a Rh catalyst leads to cyclization to an a-vinyl cyclopentanone.1543 An yne–diene can also be used for the Pauson–Khand reaction.1544 SiMe3 SiMe3 Co2(CO)8, CO 90 °C, 36 h O heptane, sealed tube MOMO MOMO H 108 The reaction can be promoted photochemically1545 and the rate is enhanced by the presence of primary amines.1546 Coordinating ligands also accelerate the reaction,1547 polymer-supported promoters have been developed1548 and there are many possible variations in reaction conditions.1549 The Pauson–Khand reaction has been done under heterogeneous reaction conditions,1550 with Co nanoparticles,1551 and in water.1552 A See Krafft, M.E.; Hirosawa, C.; Bonaga, L.V.R Tetrahedron Lett 1999, 40, 9177 See Krafft, M.E.; Bo~naga, L.V.R.; Hirosawa, C J Org Chem 2001, 66, 3004 1535 Koga, Y.; Kobayashi, T.; Narasaka, K Chem Lett 1998, 249 An entrapped-Rh catalyst has been used: Park, K.H.; Son, S.U.; Chung, Y.K Tetrahedron Lett 2003, 44, 2827 1536 Hicks, F.A.; Kablaoui, N.M.; Buchwald, S.L J Am Chem Soc 1997, 118, 9450; Hicks, F.A.; Kablaoui, N.M.; Buchwald, S.L J Am Chem Soc 1999, 121, 5881 1537 Adrio, J.; Carretero, J.C J Am Chem Soc 2007, 129, 778; Adrio, J.; Rivero, M.R.; Carretero, J.C Org Lett 2005, 7, 431 1538 Hoye, T.R.; Suriano, J.A J Am Chem Soc 1993, 115, 1154 1539 Khand, I.U.; Pauson, P.L.; Habib, M.J J Chem Res (S) 1978, 348; Khand, I.U; Pauson, P.L J Chem Soc Perkin Trans 1, 1976, 30 Gibson, S.E.; Stevenazzi, A Angew Chem Int Ed 2003, 42, 1800; Gibson, S.E.; Mainolfi, N Angew Chem Int Ed 2005, 44, 3022; Lee, H.-W.; Kwong, F.-Y Eur J Org Chem 2010, 789 1540 See de Bruin, T.J.M.; Milet, A.; Greene, A.E.; Gimbert, Y J Org Chem 2004, 69, 1075 See also, Rivero, M.R.; Adrio, J.; Carretero, J.C Eur J Org Chem 2002, 2881 1541 Magnus, P.; Principe, L.M Tetrahedron Lett 1985, 26, 4851 1542 Itami, K.; Mitsudo, K.; Fujita, K.; Ohashi, Y.; Yoshida, J.-i J Am Chem Soc 2004, 126, 11058 1543 Wender, P.A.; Croatt, M.P.; Deschamps, N.M J Am Chem Soc 2004, 126, 5948 1544 Wender, P.A; Deschamps, N.M.; Gamber, G.G Angew Chem Int Ed 2003, 42, 1853 1545 Pagenkopf, B.L.; Livinghouse, T J Am Chem Soc 1996, 118, 2285 1546 Sugihara, T.; Yamada, M.; Ban, H.; Yamaguchi, M.; Kaneko, C Angew Chem Int Ed 1997, 36, 2801 1547 Krafft, M.E.; Scott, I.L.; Romero, R.H Tetrahedron Lett 1992, 33, 3829 1548 Kerr, W.J.; Lindsay, D.M.; McLaughlin, M.; Pauson, P.L Chem Commun 2000, 1467; Brown, D.S.; Campbell, E.; Kerr, W.J.; Lindsay, D.M.; Morrison, A.J.; Pike, K.G.; Watson, S.P Synlett 2000, 1573 1549 Krafft, M.E.; Bo~naga, L.V.R.; Wright, J.A.; Hirosawa, C J Org Chem 2002, 67, 1233; Blanco- Urgoiti, J.; Casarrubios, L.; Domınguez, G.; Perez-Castells, J Tetrahedron Lett 2002, 43, 5763 The reaction has been done in aqueous media: Krafft, M.E.; Wright, J.A.; Bo~ naga, L.V.R Tetrahedron Lett 2003, 44, 3417 1550 Kim, S.-W.; Son, S.U.; Lee, S.I.; Hyeon, T.; Chung, Y.K J Am Chem Soc 2000, 122, 1550 1551 Kim, S.-W.; Son, S.U.; Lee, S.S.; Hyeon, T.; Chung, Y.K Chem Commun 2001, 2212; Son, S.U.; Lee, S.I.; Chung, Y.K.; Kim, S.-W.; Hyeon, T Org Lett 2002, 4, 277 1552 Krafft, M.E.; Wright, J.A.; Llorente, V.R.; Bo~naga, L.V.R Can J Chem 2005, 83, 1006 1533 1534 REACTIONS 977 dendritic Co catalyst has been used.1553 Ultrasound promoted1554 and microwave promoted1555 reactions have been developed Polycyclic compounds (tricyclic and higher) are prepared in a relatively straightforward manner using this reaction.1556 Asymmetric Pauson–Khand reactions are known.1557 The Pauson–Khand reaction is compatible with other groups or heteroatoms elsewhere in the molecule These include ethers and aryl halides,1558 esters,1559 amides,1560 alcohols,1561 diols,1562 and an indole unit.1563 A silicon-tethered Pauson–Khand reaction is known.1564 Allenes are reaction partners in the Pauson–Khand reaction.1565 This type of reaction can be extended to form six-membered rings using a Ru catalyst.1566 A doublePauson–Khand process was reported.1567 In some cases, an aldehyde can serve as the source of the carbonyl for carbonylation.1568 R1 R OC OC Co OC R Co2(CO)8 OC Co CO R2 R1 OC OC Co OC R OC OC Co OC R CO Co CO CO OC R1 O Co R2 R1 OC OC CO Co OC Co OC R2 R R1 O O OC OC – Co2(CO)4 R R2 Co OC Co R OC R1 109 R R R2 The accepted mechanism was proposed by Magnus and Principe,1569 shown for the formation of 109,1570 and supported by Krafft’s work.1571 It has been shown that CO is lost from the Pauson–Khand complex prior to alkene coordination and insertion.1572 Calculations Dahan, A.; Portnoy, M Chem Commun 2002, 2700 Ford, J.G.; Kerr, W.J.; Kirk, G.G.; Lindsay, D.M.; Middlemiss, D Synlett 2000, 1415 1555 Iqbal, M.; Vyse, N.; Dauvergne, J.; Evans, P Tetrahedron Lett 2002, 43, 7859 1556 Ishizaki, M.; Iwahara, K.; Niimi, Y.; Satoh, H.; Hoshino, O Tetrahedron 2001, 57, 2729; Son, S.U.; Yoon, Y.A.; Choi, D.S.; Park, J.K.; Kim, B.M.; Chung, Y.K Org Lett 2001, 3, 1065 1557 Verdaguer, X.; Moyano, A.; Pericas, M.A.; Riera, A.; Maestro, M.A.; Mahıa, J J Am Chem Soc 2000, 122, 10242l; Konya, D.; Robert, F.; Gimbert, Y.; Greene, A.E Tetrahedron Lett 2004, 45, 6975 1558 Perez-Serrano, L.; Banco-Urgoiti, J.; Casarrubios, L.; Domınguez, G.; Perez-Castells, J J Org Chem 2000, 65, 3513 For a review, see Suh W.H.; Choi, M.; Lee, S.I.; Chung, Y.K Synthesis 2003, 2169 1559 Krafft, M.E.; Bo~ naga, L.V.R Angew Chem Int Ed 2000, 39, 3676, and references cited therein; Jeong, N.; Sung, B.S.; Choi, Y.K J Am Chem Soc 2000, 122, 6771; Sturla, S.J.; Buchwald, S.L J Org Chem 2002, 67, 3398 1560 Comely, A.C.; Gibson, S.E.; Stevenazzi, A.; Hales, N.J Tetrahedron Lett 2001, 42, 1183 1561 Blanco-Urgoiti, J.; Casarrubios, L.; Domınguez, G.; Perez-Castells, J Tetrahedron Lett 2001, 42, 3315 1562 Mukai, C.; Kim, J.S.; Sonobe, H.; Hanaoka, M J Org Chem 1999, 64, 6822 1563 Perez-Serrano, L.; Domınguez, G.; Perez-Castells, J J Org Chem 2004, 69, 5413 1564 Brummond, K.M.; Sill, P.C.; Rickards, B.; Geib, S.J Tetrahedron Lett 2002, 43, 3735; Reichwein, J.F.; Iacono, S.T.; Patel, U.C.; Pagenkopf, B.L Tetrahedron Lett 2002, 43, 3739 1565 Brummond, K.M.; Chen, H.; Fisher, K.D.; Kerekes, A.D.; Rickards, B.; Sill, P.C.; Geib, A.D Org Lett 2002, 4, 1931 See Shibata, T.; Kadowaki, S.; Hirase, M.; Takagi, K Synlett 2003, 573 1566 Trost, B.M.; Brown, R.E.; Toste, F.D J Am Chem Soc 2000, 122, 5877 1567 Rausch, B.J.; Gleiter, R Tetrahedron Lett 2001, 42, 1651 1568 See Shibata, T.; Toshida, N.; Takagi, K J Org Chem 2002, 67, 7446; Morimoto, T.; Tsutsumi, K.; Kakiuchi, K Tetrahedron Lett 2004, 45, 9163 1569 Magnus, P.; Principe, L.M Tetrahedron Lett 1985, 26, 4851 1570 For a review, see Brummond, K.M.; Kent, J.L Tetrahedron 2000, 56, 3263 1571 Krafft, M.E Tetrahedron Lett 1988, 29, 999 1572 Gimbert, Y.; Lesage, D.; Milet, A.; Fournier, F.; Greene, A.E.; Tabet, J.-C Org Lett 2003, 5, 4073 See Robert, F.; Milet, A.; Gimbert, Y.; Konya, D.; Greene, A.E J Am Chem Soc 2001, 123, 5396 1553 1554 978 ADDITION TO CARBON–CARBON MULTIPLE BONDS concluded that the LUMO of the coordinated alkene plays a crucial role in alkene reactivity by determining the degree of back-donation in the complex.1573 Other carbonylation methods are available Carbonylation occurs with conjugated ketones to give 1.4-diketones, using phenylboronic acid (see Reaction 13-12), CO and a Rh catalyst.1574 A noncarbonylation route treated a conjugated diene with an excess of tert-butyllithium, and quenching with CO2 led to a cyclopentadienone.1575 When quenched with CO rather than CO2, a nonconjugated cyclopentenone was formed.1576 Note that a carbonylation reaction with CO, a diyne, and an Ir1577 or a Co catalyst1578 provided similar molecules With any method, if the alkene contains a functional group (e.g., OH, NH2, or CONH2), the corresponding lactone (Reaction 16-63),1579 lactam (Reaction 16-74), or cyclic imide may be the product.1580 Titanium,1581 Pd,1582 Ru,1583 and Rh1584 catalysts have been used to generate lactones Allenic alcohols are converted to butenolides with 10 atm of CO and a Ru catalyst.1585 Larger ring conjugated lactones can also be formed by this route using the appropriate allenic alcohol.1586 Propargylic alcohols lead to b-lactones1587 or to butenolides with CO/H2O and a Rh catalyst.1588 Allenic tosyl-amides are converted to N-tosyl a,b-unsaturated pyrrolidinones using 20 atm of CO and a Ru catalyst.1589 Conjugated imines are converted to similar products with CO, ethylene, and a Ru catalyst.1590 Propargyl alcohols generate lactones when treated with a chromium pentacarbonyl carbene complex.1591 Amines add to allenes, in the presence of CO and a Pd catalyst, to form conjugated amides.1592 The reaction of a secondary amine, CO, a terminal alkyne, and t-BuMe2SiH with a 1593 Reaction Rh catalyst led to a conjugated amide bearing the silyl group of the CÀ ÀC unit of a molecule containing an amine and an alkene unit was carboxylated with CO in the presence of a Pd catalyst to give a lactam.1594 A similar reaction with a molecule containing an amine and an alkyne also generated a lactam, in the presence of CO and de Bruin, T.J.M.; Milet, A.; Greene, A.E.; Gimbert, Y J Org Chem., 2004 69, 1075 Sauthier, M.; Castanet, Y.; Mortreux, A Chem Commun 2004 1520 1575 Xi, Z.; Song, Q J Org Chem 2000, 65, 9157 1576 Song, Q.; Chen, J.; Jin, X.; Xi, Z J Am Chem Soc 2001, 123, 10419; Song, Q.; Li, Z.; Chen, J.; Wang, C.; Xi, Z Org Lett 2002, 4, 4627 1577 Shibata, T.; Yamashita, K.; Katayama, E.; Takagi, K Tetrahedron 2002, 58, 8661 1578 Sugihara, T.; Wakabayashi, A.; Takao, H.; Imagawa, H.; Nishizawa, M Chem Commun 2001, 2456 1579 Dong, C.; Alper, H J Org Chem 2004, 69, 5011 1580 See Ohshiro, Y.; Hirao, T Heterocycles 1984, 22, 859; Falbe, J New Syntheses with Carbon Monoxide, Springer, NY, 1980, pp 147–174 See Krafft, M.E.; Wilson, L.J.; Onan, K.D Tetrahedron Lett 1989, 30, 539 1581 Kablaoui, N.M.; Hicks, F.A.; Buchwald, S.L J Am Chem Soc 1997, 119, 4424 1582 El Ali, B.; Okuro, K.; Vasapollo, G.; Alper, H J Am Chem Soc 1996, 118, 4264 Also see, Brunner, M.; Alper, H J Org Chem 1997, 62, 7565 1583 Kondo, T.; Kodoi, K.; Mitsudo, T.-a.; Watanabe, Y J Chem Soc., Chem Commun 1994, 755 1584 Yoneda, E.; Kaneko, T.; Zhang, S.-W.; Takahashi, S Tetrahedron Lett 1998, 39, 5061 1585 Yoneda, E.; Kaneko, T.; Zhang, S.-W.; Onitsuka, K.; Takahashi, S Org Lett 2000, 2, 441 1586 Yoneda, E.; Zhang, S.-W.; Onitsuka, K.; Takahashi, S Tetrahedron Lett 2001, 42, 5459 1587 Ma, S.; Wu, B.; Zhao, S Org Lett 2003, 5, 4429 1588 Fukuta, Y.; Matsuda, I.; Itoh, K Tetrahedron Lett 2001, 42, 1301 1589 Kang, S.-K.; Kim, K.-J.; Yu, C.-M.; Hwang, J.-W.; Do, Y.-K Org Lett 2001, 3, 2851 1590 Chatani, N.; Kamitani, A.; Murai, S J Org Chem 2002, 67, 7014 1591 Good, G.M.; Kemp, M.I.; Kerr, W.J Tetahedron Lett 2000, 41, 9323 1592 Grigg, R.; Monteith, M.; Sridharan, V.; Terrier, C Tetrahedron 1998, 54, 3885 1593 Matsuda, I.; Takeuchi, K.; Itoh, K Tetrahedron Lett 1999, 40, 2553 1594 Okuro, K.; Kai, H.; Alper, H Tetrahedron Asymmetry 1997, 8, 2307 1573 1574 REACTIONS 979 a Rh catalyst.1595 An intramolecular carbonylation reaction of a conjugated imine, with CO, ethylene and a Ru catalyst, led to a highly substituted b,g-unsaturated lactam.1596 15-37 Hydroformylation Hydro-formyl-addition + CO + H2 [Co(CO)4]2 pressure H CHO Alkenes can be hydroformylated1597 by treatment with CO and hydrogen over a catalyst, usually a Co carbonyl (see below for a description of the mechanism) or a Rh complex,1598 but other transition metal compounds have also been used Cobalt catalysts are less active than the Rh type, and catalysts of other metals are generally less active.1599 Commercially, this is called the oxo process, but it can be carried out in the laboratory in an ordinary hydrogenation apparatus The order of reactivity is straight-chain terminal alkenes > straight-chain internal alkenes > branched-chain alkenes With terminal alkenes, for example, the aldehyde unit is formed on both the primary and secondary carbon, but proper choice of catalyst and additive leads to selectivity for the secondary1600 or primary product.1601 Alkylidenecyclopropane derivatives undergo hydroformylation to give aldehydes with a quaternary center.1602 Good yields for hydroformylation have been reported using Rh catalysts in the presence of certain other additives.1603 Among the side reactions are the aldol Reaction (16-34), acetal formation, the Tischenko Reaction (19-82), and polymerization In one case using a Rh catalyst, 2-octene gave nonanal, presumably via a h3-allyl complex (Sec 3.C).1604 Conjugated dienes give dialdehydes when Rh catalysts are used1605 but saturated monoaldehydes (the second double bond is reduced) with cobalt carbonyls Both 1,4and 1,5-dienes may give cyclic ketones.1606 Hydroformylation of triple bonds proceeds very slowly, and few examples have been reported.1607 However, in the presence of a Rh catalyst, the triple bond of a conjugated Shiba, T.; Zhou, D.-Y.; Onitsuka, K.; Takahashi, S Tetrahedron Lett 2004, 45, 3211 Berger, D.; Imhof, W Tetrahedron 2000, 56, 2015 1597 See Kalck, P.; Peres, Y.; Jenck, J Adv Organomet Chem 1991, 32, 121; Davies, J.A in Hartley, F.R.; Patai, S The Chemistry of the Metal–Carbon Bond, Vol 3, Wiley, NY, 1985, pp 361–389; Collman, J.P.; Hegedus, L.S.; Norton, J.R.; Finke, R.G Principles and Applications of Organotransition Metal Chemistry, University Science Books, Mill Valley, CA 1987, pp 621–632; Pino, P J Organomet Chem 1980, 200, 223; Falbe, J Carbon Monoxide in Organic Synthesis Springer, NY, 1980, pp 3–77 See Ohshiro, Y.; Hirao, T Heterocycles 1984, 22, 859 1598 See Amer, I.; Alper, H J Am Chem Soc 1990, 112, 3674; Jardine, F.H in Hartley, F.R The Chemistry of the Metal-Carbon Bond, Vol 4, Wiley, NY, 1987, pp 733–818, pp 778–784 1599 Collman, J.P.; Hegedus, L.S.; Norton, J.R.; Finke, R.G Principles and Applications of Organotransition Metal Chemistry, University Science Books, Mill Valley, CA 1987, p 630 1600 Chan, A.S.C.; Pai, C.-C.; Yang, T.-K.; Chen, S.M J Chem Soc., Chem Commun 1995, 2031; Doyle, M.P.; Shanklin, M.S.; Zlokazov, M.V Synlett 1994, 615 1601 Breit, B.; Seiche, W J Am Chem Soc 2003, 125, 6608 1602 Simaan, S.; Marek, I J Am Chem Soc 2010, 132, 4066 1603 Johnson, J.R.; Cuny, G.D.; Buchwald, S.L Angew Chem Int Ed 1995, 34, 1760 1604 van der Veen, L.A.; Kamer, P.C.J.; van Leeuwen, P.W.N.M Angew Chem Int Ed 1999, 38, 336 1605 Fell, B.; Rupilius, W Tetrahedron Lett 1969, 2721 1606 See Mullen, A in Falbe, J New Syntheses with Carbon Monoxide, Springer, NY, 1980, pp 414–439 See also, Eilbracht, P.; H€ uttmann, G.; Deussen, R Chem Ber 1990, 123, 1063, and other papers in this series 1607 See Botteghi, C.; Salomon, C Tetrahedron Lett 1974, 4285 For an indirect method, see Campi, E.; Fitzmaurice, N.J.; Jackson, W.R.; Perlmutter, P.; Smallridge, A.J Synthesis 1987, 1032 1595 1596 980 ADDITION TO CARBON–CARBON MULTIPLE BONDS enyne is formylated.1608 The Rh catalyzed reaction can be regioselective.1609 Many functional groups (e.g., OH, CHO, CO2R,1610 CN), can be present in the molecule, although halogens usually interfere Stereoselective syn addition has been reported,1611 and also stereoselective anti addition.1612 Asymmetric hydroformylation of alkenes has been accomplished with a chiral catalyst,1613 and in the presence of chiral additives.1614 The choice of ligand is important in such reactions.1615 Cyclization to prolinal derivatives has been reported with allylic amines.1616 When dicobalt octacarbonyl [Co(CO)4]2 is the catalyst, the species that actually adds to the double bond is tricarbonylhydrocobalt [HCo(CO)3].1617 Carbonylation [RCo(CO)3 ỵ Co CO ! RCo(CO)4] takes place followed by a rearrangement and a reduction of the CÀ bond, similar to steps and of the nickel carbonyl mechanism shown in Reaction 15-35 The reducing agent in the reduction step is tetracarbonylhydrocobalt [HCo(CO)4],1618 or, under some conditions, H2.1619 When HCo(CO)4 was the agent used to hydroformylate styrene, the observation of CIDNP (Sec 5.C.i) indicated that the mechanism is different, and involves free radicals.1620 Key intermediates have been detected in the Co catalyzed hydroformylation reaction.1621 Alcohols can be obtained by allowing the reduction to continue after all the CO is used up It has been shown1622 that the formation of alcohols is a second step, occurring after the formation of aldehydes, and that HCo(CO)3 is the reducing agent OS VI, 338 15-38 Addition of HCN Hydro-cyano-addition + HCN H CN Ordinary alkenes not react with HCN, but polyhalo alkenes and alkenes of the form À ÀCÀÀZ add HCN to give nitriles.1623 The reaction is therefore a nucleophilic addition CÀ À van den Hoven, B.G.; Alper, H J Org Chem 1999, 64, 3964 Kuil, M.; Soltner, T.; van Leeuwen, P.W.N.M.; Reek, J.N.H J Am Chem Soc 2006, 128, 11344 1610 See Hu, Y.; Chen, W.; Osuna, A.M.B.; Stuart, A.M.; Hope, E.G.; Xiao, J Chem Commun 2001, 725 1611 See Haelg, P.; Consiglio, G.; Pino, P Helv Chim Acta 1981, 64, 1865 1612 Krauss, I.J.; Wang, C.C-Y.; Leighton, J.L J Am Chem Soc 2001, 123, 11514 1613 Ojima, I.; Hirai, K in Morrison, J.D Organic Synthesis Vol 5, Wiley, NY, 1985, pp 103–145, pp 125–139; Breit, B.; Seiche, W Synthesis 2001, 1; Clark, T.P.; Landis, C.R.; Freed, S.L.; Klosin, J.; Abboud, K.A J Am Chem Soc 2005, 127, 5040; Yan, Y.; Zhang, X J Am Chem Soc 2006, 128, 7198; Watkins, A.L.; Hashiguchi, B G.; Landis, C.R Org Lett 2008, 10, 4553 1614 Sakai, N.; Nozaki, K.; Takaya, H J Chem Soc., Chem Commun 1994, 395 See Gladiali, S.; Bayon, J.C.; Claver, C Tetrahedron Asymmetry 1995, 6, 1453 1615 Klosin, J.; Landis, C.R Acc Chem Res 2007, 40, 1251 1616 Anastasiou, D.; Campi, E.M.; Chaouk, H.; Jackson, W.R.; McCubbin, Q.J Tetrahedron Lett 1992, 33, 2211 1617 Mirbach, M.F J Organomet Chem 1984, 265, 205 For the mechanism see Orchin, M Acc Chem Res 1981, 14, 259; Versluis, L.; Ziegler, T.; Baerends, E.J.; Ravenek, W J Am Chem Soc 1989, 111, 2018 1618 Ungvary, F.; Marko, L Organometallics 1982, 1, 1120 1619 See Kovacs, I.; Ungvary, F.; Marko, L Organometallics 1986, 5, 209 1620 Bockman, T.M.; Garst, J.F.; King, R.B.; Marko, L.; Ungvary, F J Organomet Chem 1985, 279, 165 1621 Godard, C.; Duckett, S.B.; Polas, S.; Tooze, R.; Whitwood, A.C J Am Chem Soc 2005, 127, 4994 1622 Aldridge, C.L.; Jonassen, H.B J Am Chem Soc 1963, 85, 886 1623 See Friedrich, K in Patai, S.; Rappoport, Z The Chemistry of Functional Groups, Supplement C pt 2, Wiley, NY, 1983, pp 1345–1390; Nagata, W.; Yoshioka, M Org React 1977, 25, 255; Brown, E.S in Wender, I.; Pino, P Organic Syntheses via Metal Carbonyls, Vol 2, Wiley, NY, 1977, pp 655–672 1608 1609 REACTIONS 981 and is base catalyzed Hydrogen cyanide can be added to ordinary alkenes in the presence of dicobalt octacarbonyl1624 or certain other transition metal compounds.1625 When Z is COR or, more especially, CHO, 1,2-addition (Reaction 16-53) is an important competing reaction and may be the only reaction An acid-catalyzed hydrocyanation is also known.1626 Triple bonds react very well when catalyzed by an aqueous solution of CuCl, NH4Cl, and HCl or by Ni or Pd compounds.1627 The HCN can be generated in situ from acetone cyanohydrin (see Reaction 16-52), avoiding the use of the poisonous HCN.1628 Alkenes react with HCN via this procedure to give a nitrile in the presence of a Ni complex.1629 One or molar equivalents of HCN can be added to a triple bond, since the initial product is a Michael-type substrate Acrylonitrile is commercially prepared this way, by the addition of HCN to acetylene Alkylaluminum cyanides (e.g., Et2AlCN), or mixtures of HCN and trialkylalanes (R3Al) are especially good reagents for conjugate addition of HCN1630 to a,b-unsaturated ketones and a,b-unsaturated acyl halides An indirect method for the addition of HCN to ordinary alkenes uses an isocyanide (RNC) and Schwartz’s reagent (see Reaction 15-17); this method gives anti-Markovnikov addition.1631 tert-Butyl 1632 isocyanide and TiCl4 have been used to add HCN to CÀ Pretreatment ÀCÀÀZ alkenes with NaI/Me3SiCl followed by CuCN converts alkynes to vinyl nitriles.1633 When an alkene is treated with Me3SiCN and AgClO4, followed by aq NaHCO3, the product is the isonitrile (RNC) formed with Markovnikov selectivity.1634 Enantioselective cyanation using TMSCN and HCN, and a Gd catalyst, leads to b-cyano amides.1635 OS I, 451; II, 498; III, 615; IV, 392, 393, 804; V, 239, 572; VI, 14 For addition of ArH, see Reaction 11-12 (Friedel–Crafts alkylation) 15.C.iii Reactions in Which Hydrogen Adds to Neither Side Some of these reactions are cycloadditions (Reactions 15-50, 15-62, 15-54, and 15-57–15-66) In such cases, addition to the multiple bond closes a ring: W + W Y Y Arthur, Jr., P.; England, D.C.; Pratt, B.C.; Whitman, G.M J Am Chem Soc 1954, 76, 5364 See Brown, E.S in Wender, P.; Pino, P Organic Syntheses via Metal Carbonyls, Vol 2, Wiley, NY, 1977, pp 658–667; Tolman, C.A.; McKinney, R.J.; Seidel, W.C.; Druliner, J.D.; Stevens, W.R Adv Catal 1985, 33, For studies of the mechanism see McKinney, R.J.; Roe, D.C J Am Chem Soc 1986, 108, 5167; Funabiki, T.; Tatsami, K.; Yoshida, S J Organomet Chem 1990, 384, 199 See also, Bini, L.; M€uller, C.; Vogt, D Chem Commun 2010, 8325 1626 Yanagisawa, A.; Nezu, T.; Mohri, S.-i Org Lett 2009, 11, 5286 1627 Jackson, W.R.; Lovel, C.G Aust J Chem 1983, 36, 1975 1628 Jackson, W.R.; Perlmutter, P Chem Br 1986, 338 1629 Yan, M.; Xu, Q.-Y.; Chan, A.S.C Tetrahedron Asymmetry 2000, 11, 845 1630 See Nagata, W.; Yoshioka, M Org React 1977, 25, 255 1631 Buchwald, S.L.; LeMaire, S.J Tetrahedron Lett 1987, 28, 295 1632 Ito, Y.; Kato, H.; Imai, H.; Saegusa, T J Am Chem Soc 1982, 104, 6449 1633 Luo, F.-T.; Ko, S.-L.; Chao, D.-Y Tetrahedron Lett 1997, 38, 8061 1634 Kitano, Y.; Chiba, K.; Tada, M Synlett 1999, 288 1635 Mita, T.; Kazuki, K.; Kanai, M.; Shibasaki, M J Am Chem Soc 2005, 127, 514 1624 1625 982 ADDITION TO CARBON–CARBON MULTIPLE BONDS A Halogen on One or Both Sides 15-39 Halogenation of Double and Triple Bonds (Addition of Halogen, Halogen) Dihalo-addition Br + Br2 Br Most double bonds are easily halogenated1636 with bromine, chlorine, or inter-halogen compounds.1637 Substitution can compete with addition in some cases.1638 Iodination has also been accomplished, but the reaction is slower.1639 Under free radical conditions, iodination proceeds more easily.1640 However, vic-diiodides are generally unstable and tend to revert to iodine and the alkene X X + + X–X X X 110 The mechanism is usually electrophilic (see Sec 15.A.i), involving formation of an halonium ion (Reaction 110),1641 followed by nucleophilic ring opening to give the vicdihalide Nucleophilic attack occurs with selectivity for the less substituted carbon When free radical initiators (or UV light) are present, addition can occur by a free radical mechanism.1642 Once Br or Cl radicals are formed, however, substitution may compete (Reactions 14-1 and 14-3) This is especially important when the alkene has allylic or benzylic hydrogen atoms Under free radical conditions (UV light) bromine or chlorine adds to a benzene substituent to give, respectively, hexabromo- and hexachlorocyclohexane These are mixtures of stereoisomers (see Sec 4.K.ii).1643 Under ordinary conditions fluorine itself is too reactive to give simple addition, and mixtures are obtained.1644 However, F2 has been successfully added to certain double bonds in an inert solvent at low temperatures (À78  C), usually by diluting the F2 gas with Ar or N2.1645 Addition of fluorine has also been accomplished with other reagents (e.g., p-Tol-IF2/Et3NÁ5 HF),1646 and a mixture of PbO2 and SF4.1647 The Au catalyzed reaction of Et3NÀÀHF with alkynes gives vinyl fluorides.1648 Larock, R.C Comprehensive Organic Transformations, 2nd ed., Wiley–VCH, NY, 1999, pp 629–632 de la Mare, P.B.D Electrophilic Halogenation Cambridge University Press, Cambridge, 1976; House, H.O Modern Synthetic Reaction, 2nd ed., W.A Benjamin, NY, 1972, pp 422–431 1638 McMillen, D.W.; Grutzner, J.B J Org Chem 1994, 59, 4516 1639 Zanger, M.; Rabinowitz, J.L J Org Chem 1975, 40, 248 1640 Ayres, R.L.; Michejda, C.J.; Rack, E.P J Am Chem Soc 1971, 93, 1389 1641 See Lenoir, D.; Chiappe, C Chem Eur J 2003, 9, 1037 For a theoretical study of these intermediates, see Okazaki, T.; Laali, K.K J Org Chem 2005, 70, 9139 Also see Zabalov, M.V.; Karlov, S.S.; Lemenovskii, D.A.; Zaitseva, G.S J Org Chem 2005, 70, 9175 1642 See Dessau, R.M J Am Chem Soc 1979, 101, 1344 1643 See Cais, M in Patai, S The Chemistry of Alkenes, Vol 1, Wiley, NY, 1964, pp 993 1644 See Fuller, G.; Stacey, F.W.; Tatlow, J.C.; Thomas, C.R Tetrahedron 1962, 18, 123 1645 Rozen, S.; Brand, M J Org Chem 1986, 51, 3607 1646 Hara, S.; Nakahigashi, J.; Ishi-i, K.; Sawaguchi, M.; Sakai, H.; Fukuhara, T.; Yoneda, N Synlett 1998, 495 1647 Bissell, E.R.; Fields, D.B J Org Chem 1964, 29, 1591 1648 Akana, J.A.; Bhattacharyya, K.X.; M€uller, P.; Sadighi, J.P J Am Chem Soc 2007, 129, 7736 1636 1637 SUBJECT INDEX sulfoxides, allylic, and [2,3]Wittig rearrangement, 1414 and 1,4-elimination, 1296 sulfoxides, and atropisomers, 131 and chirality, 129 and conformation, 189 and NCS, 674 and radical elimination, 1296 and resonance, 49 and tetrahedral intermediates, 129 and Umpolung, 553 and ylids, 49 sulfoxides, aryl, from aromatic compounds, 602 by oxidation of sulfides, 1303 by oxidation of thioethers, 1493 by oxidation of thioethers, enantioselectivity, 1494 catalytic hydrogenation, 851 conjugated with organocuprates, 950 conversion to aldehydes, 553 desulfurization, reagents, 1551 elimination, Hofmann’s rule and Zaitsev’s rule, 1296 elimination, mechanism, 1296 from organometallics, 703 from sulfonic acid esters, 703 sulfoxides, halogenation, 674 halogenation, reagents for, 674 inversion, 129 keto, 1296 oxidation with hydroperoxide, mechanism, 1495 pyrolysis to alkenes, 1295 reagents for oxidation, 1494 rearrangement to acetoxy sulfides, 1565 sulfoxides, reduction, 540 and isotope labeling, 1553 to sulfones, reagents, 1553 to thioethers, reagents, 1552 sulfoxides, resolution of, 1494 thermal elimination, mechanism, 1296 treatment with anhydrides, 1565 with aromatic compounds, 632 with aryl halides, 890 with DAST, 674 with NBS, 674 sulfoxonium compounds, pyrolysis to alkenes, 1295 sulfur compounds, and optical activity, 129 sulfur dichloride, and chlorosulfenation, 837 sulfur dioxide, and superacids, 210 and the Reed reaction, 837 as a guest, 114 as a leaving group, 1302, 1303, 1318 as solvent, 382 liquid, 428 with alkenes and halogen, 837 with organometallics, 703 with silyl enol ethers, 1251 sulfur electrophiles, 600, 680, 703 sulfur groups, and radical cyclization, 963 sulfur hexafluoride, and electronic structure, 15 sulfur monochloride, with alkynes, 1006 sulfur nucleophiles, 475, 1087 sulfur reagents, chiral, 1494 sulfur tetrafluoride, with aldehydes or ketones, 1106 sulfur trioxide, and DMSO, for oxidation of alcohols, 1448 and sulfonation, 601 as an electrophile, 601, 602 sulfonation of carbonyl compounds, 681 sulfonation of ketones, 680 with aromatic compounds, 601 with trihalides to give acyl halides, 453 sulfur ylids see ylids sulfur ylids, 50, 799 in ionic liquids, 1179 phase transfer conditions, 1176 sulfur-35, 1553 sulfur, and aromatization, 1438 and carbanions stabilization, 228 and carbonylation of amines, 730 and hydrogen bonds, 101 as a poison in catalytic hydrogenation, 903 chiral, 541 inversion, of configuration, 129, 1248 reactivity with nucleophiles, 1249 stabilization of carbanions, 225 stabilization of organolithium reagents, 232 substitution, isotopic labeling, 1248, 1249 substitution, kinetics, 1249 substitution, SN2 mechanism, 1249 sulfonyl see sulfonyl sulfur with diazo compounds, 1178 with diazonium salts, 1178 with Grignard reagents, 703 with organometallics, 703 with phosphoranes, 838 sulfuric acid, and arylsulfonic acids, 645 and dehydration of alcohols, 1283 and esterification, 1204 2033 and nitration of aromatic compounds, 595 and sulfonation, 601 and the Jacobsen reaction, 645 and ylids, 49 catalyst for the Schmidt reaction, 1363 electronic structure, 15 for cleavage of ethers, 454 fuming, with aromatic compounds, 600 with aromatic compounds, 600 with diols, 1343 sulfurization, organolithium reagents, 703 reagents for, 1089 sulfuryl chloride, 823 halogenation of aromatic compounds, 605 radical halogenation, 823 with Grignard reagents, 703 with peroxides, 817 sultones, from alkenes and sulfonate halides, 893 super hydride, 1502 reduction of alkyl halides, 1531 superacids see acids superacids, 214, 319, 660 and benzenonium ions, 573 and carbocation structure, 1390 and carbocations, 379, 407, 1332 and cleavage of alkanes, 725 and coupling of alkenes, 690 and diazonium salts, 434 and halogenation of aromatic compounds, 605 and hydration of alkynes, 887 and hydrogen exchange, 661 and ionization, 382 and isomerization of biphenyls, 646 and nonclassical carbocations, 403, 1340 and the Gatterman reaction, 627 formation of carbocations, 661 with alkenes, 690 superaromatic, 78 superbases, 322, 695 and transesterification, 1207 supercritical, alcohol, reduction of ketones, 1542 ammonia, 364 supercritical, carbon dioxide also see carbon dioxide supercritical, carbon dioxide, and oxidation of alcohols, 1442 and the Heck reaction, 766 aryl halides with amines, 751 carbonylation of aryl halides, 781 ethane, hydrogenation of aromatic compounds, 913 2034 SUBJECT INDEX supercritical, carbon dioxide, and oxidation of alcohols (Continued ) for alkene isomerization and the Heck reaction, 766 for enzymatic carboxylation, 630 for enzymatic reductions, 1510 in the Kolbe-Schmidt reaction, 629 2-propanol, and reduction, 1508 water, and pinacol rearrangement, 1342 water, and the Beckmann rearrangement, 1366 superelectrophilicity, 379 superheating, and microwaves, 310 superimposability, and chirality, 122, 126 and enantiomers, 136 and optical activity, 122 superoxide, potassium, with alkyl halides, 472 superoxides, with alkyl halides or sulfonate esters, 473 superphane, 82 supersonic molecular jet spectroscopy, and conformations, 174 supplementary information, journals, 1571 supplements, of Beilstein, 1579 suprafacial concerted cycloaddition, 1064 suprafacial migration, 1392, 1394 in sigmatropic rearrangement, 1392, 1393 suprafacial overlap, 1035 suprafacial rearrangements, configuration of migrating groups, 1396, 1397 supramolecular forms, 121 surface sites, heterogeneous catalysts, 907, 908 surfactants, cleavage of ethers, 504 surrogates, amino acid, 548 Survey of Organic Synthesis, 1591 Suzuki coupling see SuzukiMiyaura Suzuki coupling, 560 Suzuki reaction, 795, 889 and microwave irradiation, 311 Suzuki-Miyaura coupling, 701, 770 additives, 770 alternative metal catalysts, 773 alternative reagents, 773 Suzuki-Miyaura coupling, and acyl halides, 774 and aryl boronic acids, 774 and aryl sulfonate esters, 770 and aryl triflates, 770 and arylation of silanes, 783 and arylborates, 774 and diazonium salts, 788 and electrospray mass spectrometry, 773 and ionic liquids, 771 and microwave irradiation, 771, 775 and trifluoroborates, 775 Suzuki-Miyaura coupling, base free, 774 biaryls, atropisomers, 773 catalysts for deactivated halides, 771 chiral catalysts, 773 compatible functional groups, 772 double coupling, 772 enantioselectivity, and biaryls, 773 in aqueous media, 771 in supercritical carbon dioxide, 771 ligand free, 771 mechanism, 773 on alumina, 771 oxidative addition, 773 Pd free cross coupling, 771 polymer supported, 771 polymer-tethered reagents, 771 reaction conditions, 770 recyclable catalysts, 771 solvent effects, 770 solvent free, 771 structural variations, 772 Suzuki-Miyaura coupling, with aryldiazonium salts, 793 with carbamates, 771 with carbonates, 771 with heterocycles, 771, 772 with sulfamates, 771 with vinyl substrates, 771 Swain-Lupton s values, 359 Swain-Scott equation, 429 and Marcus theory, 429 Swern oxidation, 1482 and dehydration of amides to nitriles, 1313 and dehydration of amides, 1313 and polymer bound sulfoxide, 1447 and sulfonium salts, 1447 and sulfur substituents, 1448 of alcohols, 1447 temperature dependence, 1447 switches, molecular, 118 SYBYL, 191 sydnones, and aromaticity, 82 symmetry and chirality, 135 and aromaticity, 66 and atropisomers, 131 and biaryls, 131 and chiral compounds, 123 and chirality, 126 and circularly polarized light, 145 and dipole moment, 19 and electronegativity, 16 and enantiomers, 123 and hydrogen bonds, 99 and monocyclic compounds, 167 and orbitals, and stereogenic atoms, 126 axis, and chirality, 125 of orbitals in dienes, 1381–1386 orbital see orbital symmetry perpendicular dissymmetric planes, 130 plane, and chirality, 125 plane, and enantiomers, 125 symmetry-forbidden transitions, 292 symproportionation, addition of alkanes to alkenes, 927 syn addition, 860 bromine to alkenes, 864 dihydroxylation of alkenes, 992 of carbenes, 1055 syn elimination also see elimination, Ei syn elimination see elimination, syn syn nomenclature, 149 syn stereochemistry, in catalytic hydrogenation, 906 syn-anti dichotomy, and E2 reactions, 1258 synclinal conformation, 176, 177 synperiplanar conformation, 177 synthesis, and carbene insertion, 693 and carbenes, 255 and chiral pool, 149 and crown ethers, 109 and dediazoniation, 1550 and diastereoselectivity, 150 and microwave irradiation, 311 and reduction of aryldiazonium salts, 1550 and resolution, 149 and Robinson annulation, 1150 and sulfonate ester leaving groups, 433 and supercritical carbon dioxide, 364 and the Diels-Alder reaction, 1027 and the tetrahedral mechanism, 1074 and the Wittig reaction, 1172 synthesis, asymmetric, 143, 149– 154 and active catalysts, 153 and active reagents, 152 and active solvents, 153 and active substrates, 150 and asymmetric induction, 153 SUBJECT INDEX and chiral auxiliaries, 151, 152 and Cram’s rule, 150 and reduction of carbonyls, 152 and self-immolative reagents, 152 and the aldol condensation, 154 and the Cornforth model, 151 and the Felkin-Anh model, 151 and UV analysis, 151 chiral from achiral compounds, 151 double asymmetric synthesis, 153 with circularly polarized light, 154 with enantioselective reactions, 153 synthesis, azapagodanes, 198 by functional group type, 1605– 1629 catenanes, 119 double asymmetric, 924, 1148 enantioselective, with hydroboration, 924 Merrifield, 1218 of pyrophosphate, 112 rotaxanes, 119 stereoisomeric catenanes, 120 synthesis, stereoselective, 150, 173 and active catalysts, 153 and active reagents, 152 and active solvents, 153 and active substrates, 150 and chiral auxiliaries, 151, 152 and chiral circularly polarized light, 154 and Cram’s rule, 150 and self-immolative reagents, 152 and the aldol condensation, 154 and the Cornforth model, 151 and the Felkin-Anh model, 151 and UV analysis, 151 asymmetric induction, 153 double asymmetric synthesis, 153 enantioselective reactions, 153 reduction of carbonyls, 152 synthesis, stereospecific, 173 with alkene metathesis, 1421 with the Brook rearrangement, 1432 synthetic importance, alkene metathesis, 1419 Synthetic Methods of Organic Chemistry, 1585 synthetic targets, and the DielsAlder reaction, 1027 synthon, definition, 553 4n systems, and electrocyclic rearrangements, 1388 conrotatory versus disrotatory, 1388 4nỵ2 systems, and electrocyclic rearrangements, 1388 conrotatory versus disrotatory, 1388 table, electronegativity, 17 Tables of Experimental Dipole Moments, 1582 Tables of Interatomic Distances and Configurations in Molecules and Ions, 1582 tables, of physical data, 1581–1583 Taft equation, 356, 360 Tamao-Fleming oxidation, 468, 929 tandem metathesis, 1420 tandem vicinal difunctionalization, 951 and organocuprates, 951 tartaric acid, and enantiomers, 124 diastereomers, 147 mechanism resolution, 157 tartrates, diethyl, and Sharpless asymmetric epoxidation, 1004 tartrates, epoxidation, 1004, 1005 sodium ammonium, 157 tautomeric forms, of bullvalene, 1405 tautomerism, 89 aci form of nitro compounds, 94 and bromination of acetone, 285 and carboxylic acids, 95 and deuterium isotope effects, 666 and enamines, 94 and hydrogen bonding, 90 and hydroxypyridine, 93 and imines, 94 and mass spectrometry, 89 and microscopic reversibility, 666 and nitrosomethane, 93 and oximes, 93 and pH, 89 and pyridones, 93 and quinazolines, 94 and spirooxathianes, 94 and sugars, 94 and the Bucherer reaction, 756 and the Michael reaction, 95 tautomerism, benzoxazine, 94 decahydroquianazolines, 94 enamine-imine, 898 enol-keto, 866 imine-enamine, 94, 1180 tautomerism, keto-enol, 89, 664, 887 amides, 91 and bond energy, 91 and conformation, 665 and conjugation, 91 and enol content, 91 2035 and fluorine, 91 and NMR, 91 and solvent effects, 92 and steric hindrance, 91 and torsion strain, 666 fusion type enols, 91 mechanism, 90, 666 proton transfer, 665 solvent effects, 665 steric stabilization, 666 tautomerism, nitro compounds, 94 nitroso-oxime, 93 of enols, 664 oxocarboxylic acids, 94 phenol-keto, 93 phenol-quinone, 1408 porphycenes, 94 porphyrins, 94 proton-shift, 92, 95 ring-chain, 94 theoretical calculations, 92 tautomerism, valence, and Cope rearrangement, 1404 cycloheptatrienes-norcaradiene, 1406 oxepin-benzene oxide, 1406 tri-tert-butylcyclobutene, 1406 tautomerization, allene-alcohols, 412 amide-enol, 1239 and rate determining state, 285 tautomers, and Cope rearrangements, 1405 and hyperconjugation, 88 and mesomeric ions, 666 and Michael reactions, 867 oxime-imine, 1427 TBAF, with aziridines, 538 with silanes, 783 Tebbe’s reagent, 1173 and titanium methylene complex, 1173 with aldehydes or ketones, 1174 with lactones, 1174 Techniques of Chemistry, 1587 teflon, and microwave chemistry, 310 tellurides, from alkyl halides, 478 tellurium salts, with hexamethyldisilazide, 1177 tellurium ylids, 1169, 1177 tellurium, with Grignard reagents, 703 telomers, 867 temperature dependence, reversal of Friedel-Crafts alkylation, 641 temperature effects, and amination of alkenes, 896 2036 SUBJECT INDEX temperature, and enantiomers, 125 and enolate anion formation, 1144 and enthalpy or entropy, 265 and hyperconjugation, 287 and isotope effects, 288 and mechanism, 284 and rate, 284 and specific rotation, 125 influence of elimination, 1278 TEMPO (2,2,6,6tetramethylpiperidine-1oxyl free radical) and conversion of aldehydes to nitriles, 1096 and co-reagents used for oxidation of alcohols, 1448 and metal catalyzed oxidation of alcohols, 1448 and oxidation of aldehydes to acids, 1485 and radical cyclization, 965 metals utilized for oxidation of alcohols, 1448 oxidation in water, 1449 oxidation of alcohols in ionic liquids, 1448, 1449 polymer bound hypervalent iodine, 1449 stable radical, 240 termolecular addition, mechanism, 861 terpenes, and Robinson annulation, 1150 reduction of nitriles to methyl, 1531 terrace-type atoms, catalytic hydrogenation, 907 tervalent carbocations, 661 tervalent stereogenic atoms, 127 tetaalkylammonium halochromates, 1443 tethered Diels-Alder reactions, 1028 tethered reagents, to polymers, 771 tethers, in the Diels-Alder reaction, 1028 tetrabutylammonium fluoride (TBAF) see TBAF tetracarbonylferrate, 648 and the Tischenko reaction, 1565 sodium see sodium 2,3,5,6-tetrachloro-1,4benzoquinone see chloranil tetraenes, and homoconjugation, 43 tetrafluoroborate salts, thermolysis, 704 tetrafluoroborates, vinyl, Rh catalyst, 958, 959 tetrahydropyridines, via aza-Wittig reaction, 1173 tetrahedral intermediates, 348 and base cleavage of ketones, 723 and I strain, 350 and reactivity, 348 and sulfoxides, 129 isotope labeling, 1072 tetrahedral mechanism see mechanism tetrahedral mechanism, 1069, 1190, 1226, 1248 alcohols with acyl halides, 1200 and conformation, 1072 and isotope labeling, 1071, 1072 and leaving groups, 1073, 1074 evidence for, 1070–1072 hydrogen in catalysts, 1070 hydrolysis of carboxylic esters, 1192–1197 in acid solution, 1070 isolation of intermediates, 1071 IUPAC designation, 1070 reactivity of carbonyl substrates, 1074 spectral detection of intermediates, 1071 stereoelectronic control, 1073 synthesis transformations, 1074 tetrahedranes, 198, 1318 and strain, 198 tetrahydrofurans, by catalytic hydrogenation of furan, 913 conformation, 189 from alcohol-alkenes, 890 from allenes and alcohols, 890 from halogenation of homoallylic alcohols, 986 from oxetanes, 692 tetrahydroisoquinolines, preparation, 618 tetrahydropyrans, from alcohol alkenes, 890 tetrahydroquinolines, by cyclotrimerization, 1061 tetraions, 1302 tetrakis-triphenylphosphinopalladium(0), 41 tetramerization, of alkynes, 1059 tetramethylenediamine, as a solvent, 1294 tetramethylethylenediamine, and the Glaser reaction, 841 tetramethylpiperidine-1-oxy free radial see TEMPO tetramethylsilane, 17 tetraphenylborate, with silyl dichloride, 784 tetrapropyl perruthenate see TPAP tetrasulfides, 479 textbooks, of Organic Chemistry, 1589 thallation, mechanism, 786 thallium carboxylates, and dihydroxylation of alkenes, 995 thallium, aryl see arylthallium The Alkaloids, 1587 The Chemistry of Functional Groups, 1588 The Physico-chemical Constants of Binary Systems in Concentrated Solutions, 1582 theory, Marcus, 273, 274 thermal [2ỵ2]-cycloaddition, 1043 thermal cycloreversion, cyclobutenes, 1047 thermal effects, microwave chemistry, 310 thermal extrusion of nitrogen, 1316, 1317 thermal reactions, of alkenes, 1041 thermal stability, quaternary ammonium salts, 443 thermochemical data, and molecular mechanics, 192 thermochemistry, and frontier orbitals method, 1032 cyclotrimerization of alkynes, 1060 thermodynamic acidity see acidity thermodynamic and kinetic control, arenium ions, 576 thermodynamic conditions, enolate condensation, 543 thermodynamic control, and ambident nucleophiles, 448 and sulfur ylids, 1176 thermodynamic reactions, free energy, 272 thermodynamic stability, and alkyne isomerization, 664 and rearrangement of alkenes, 661 and rearrangement of alkenes, 664 of alkenes, 664 thermodynamically controlled reactions, 272 thermolysis, alkenes and nitric acid, 676 of alkoxides, 722 of cyclobutenes, 1380 of esters to give alkenes, 1288 of metal alkoxides, 1285 of organoboranes, 1358 of tetrafluoroborate salts, 704 of trienes, 1380 thexylborane, 921 THF, see tetrahydrofuran THF, and Grignard reagents, 231 as a solvent, 1550 complex with borane, with alkenes, 921 hydroxylation, 1476 thiacarbenium ions, 219 SUBJECT INDEX thiacrown ethers see ethers, thiacrown thia-Fries rearrangement, 637 thiazoles, aldehydes synthesis, 557 thiazolines, aldehyde synthesis, 557 thiazolium salts, and conjugate addition, 969 catalysts, 971, 1188 thiiranes, and ionic liquids, 478 and leaving groups, 432 divinyl, Cope rearrangement, 1402 elimination to alkenes, 1288 from alkenes, 1006 from alkynes and sulfur monochloride, 1006 from diazo compounds and sulfur, 1178 from epoxides, 478, 1178 from halo disulfides, 988 from halo-thioethers, 988 from thioketones and diazo compounds, 1178 from thioketones, and carbenes, 1178 halogenation of, 507 reduction to alkenes, 1502 trans-thiiration, 1006 with amines, 490 thiiranium ions, with alkenes, 1012 thiiren dioxides, 1303 thio esters, by hydration of alkynes, 888 from acyl halides and thiols, 1201 from thioacids, 1211 thioacetalization, 1088 thioacetals, from acetals, 478 hydrolysis, 457 thioacids, from carboxylic acids, 1211 with alcohols, 1211 thioaldehydes also see thioketones thioaldehydes, from aldehydes, 1088 stability, 1087, 1088 thioalkyl ketones, from enolate anions, 680 thioalkylation, of aromatic compounds, 632 thioamides, and conformation, 179 atropisomerism, 164 by hydrolysis of nitriles, 1081 catalytic hydrogenation, 851 conversion to amides, 1087 from amides, 1212 from chlorothioformates and amines, 1251 from isothiocyanates, 630, 1141 from ketones, 1566 from thioaldehydes and amines, 838 torsional barrier, 180 transamidation, 1212 with organolithium reagents, 1230 thioanisole, with butyllithium, 554 thiobenzilic acid, with aldehydes or ketones, 1320 thiocarbamates, 731 by hydrolysis of thiocyanates, 1081 conjugate addition, 968 from isothiocyanates, 1085 thiocarbonates, and the BartonMcCombie reaction, 1538 reduction to hydrocarbons, 1538 thiol surrogates, 894 with alkenes, 894, 970 thiocarbonyl compounds, from Lawesson’s reagent, 1089 thiocarbonyl ylids, [3ỵ2]cycloaddition, 1016 thiocarbonyls, and bonding, 11 thiocarbonyls, and E/Z nomenclature, 163 reagents for preparation, 1088 thiocarboxylic acids, from thiols and triflic acids, 1206 thio-Claisen rearrangement, 1411 thiocyanate ion, and S-alkylation, 497 with alkyl halides, 480 thiocyanates, alkenes with isothiocyanates, 988 and the Hoesch reaction, 633 and ultrasound, 480 aryl, from aryl diazonium salts, 791 by the Katritzky pyryliumpyridinium method, 480 from alkyl halides, 480 from amines, 480 from aryl halides, 750 from thiocyanate ion, 480 hydrolysis, 1081 thioesters with aldehydes, 1155 conjugate addition, 968 from carboxylic acids, and thiols, 1206 from thiocyanates, 633 hydrolysis, 1072 hydrolysis, kinetics, 1072 reductive desulfurization, 1552 transesterification, 1207 with boronic acids, 1231 with organocuprates, 1231 with organometallic reagents, 1231 thioether-esters, 1006 thioethers also see sulfides thioethers, alkylation, 554 thioethers, allylic vinyl, and thioClaisen rearrangement, 1411 2037 by [2,3]-Wittig rearrangement, 1413 from allylic sulfur ylids, 1413 thioethers, and DBU, 476 and phase transfer, 476 and the Williamson reaction, 476 by reduction of sulfones, 1552 by Stevens’ rearrangement of sulfur ylids, 1373 cleavage, 853 cyclic, from alkyl halides, 477, 478 desulfurization, reagents, 1551 thioethers, from addition of thiols to alkenes, 893 from alcohols, 477 from alkyl halides, 475, 476 from aromatic compounds, 632 from aryldiazonium salts, 791 from carbonates, 477 from organometallics, 703 from thiols, 475, 476 from thiophenols, 750 from thioureas, 477 thioethers, hydration of, 888 lithio, and Peterson alkenylation, 1162 thioethers, oxidation, to sulfones or sulfoxides, 1493 to sulfoxides, enantioselectivity, 1494 with hydroperoxide, mechanism, 1495 with sulfonyloxaziridines, 1494 with TPAP, 1494 thioethers, poisons in catalytic hydrogenation, 903 reagents for oxidation, 1493 reduction of sulfoxides, reagents, 1552 sodium sulfide and alkyl halides, 477 vinyl, from thiols addition to alkynes, 894 with alkyl halides, 478 with lithium naphthalenide, 852 thioformamides, by reduction of isothiocyanates, 1522 tiohydroxamic esters, 854, 855 thioketals, hydrolysis, 457 thioketenes, cycloaddition with imines, 1244 from ketones, 1088 from ketones, and hydrogen sulfide, 1087 from Lawesson’s reagent, 1089 high yield synthesis, 1088 in Diels-Alder reactions, 1038 stability, 1088 stability, and trimerization, 1087 trimerization, 1088 with boranes, 1231 with carbenes, 1178 2038 SUBJECT INDEX thioketenes, cycloaddition with imines (Continued ) with diazo compounds, 1178 thiol acids, for acyl halides and hydrogen sulfide, 1211 thiol anions see mercaptides thiol anions, as reducing agents, 1548 thiol esters, from acyl halides and thiols, 1211 from esters, 1211 thiolactams, conjugate addition of amines, 966 from isothiocyanates, 1245 from thioketenes, 1244 b-thiolactams, from thioketenes and imines, 1244 thiolate anions, conjugate addition, 968 thiolate anions, with aryl halides, 749 thiolate ions, demethylation, 477 thiols, addition, to aldehydes, 1087 to alkenes, 893 to alkenes, mechanism, 895 to alkynes, 894 to ketones, 1087 thiols, and the Chugaev reaction, 1289 anions, reaction with vinyl halides, 413 thiols, aryl see thiophenols thiols, aryl, from aryl halides, 749 by addition of hydrogen sulfide to alkenes, 894 by reduction of sulfonyl halides, 1552 catalytic hydrogenation, 851 conjugate addition, 895, 967, 968 desulfurization, reagents, 1551 from alcohols, 476, 1289 thiols, from alkyl halides, 475 from disulfides, 1555 from hydrogen sulfide, 475 from isothiouronium salts, 476 from Lawesson’s reagent, 476 from organocopper reagents, and dithiocarboxylic acids, 1132, 1133 from organometallics, 703 from silylthiols and alkenes, 894 from silyl-thiols, 476 from sodium sulfhydride, 475 from sulfonic acids, 1552 from thiourea, 476 halogenating agents, 503 internal cyclization, 478 metal mediated reaction with arylboronic acids, 750 thiols, oxidation, of disulfides, and microwaves, 1497 to disulfides, 1493 to disulfides, mechanism, 1497 to disulfides, reagents, 1497 to sulfonic acids, 1493 with chlorine and water, 1493 thiols, photochemical addition to alkenes, 895 poisons in catalytic hydrogenation, 903 reaction with alcohols, 477 reduction of disulfides, reagents, 1555 silyl, 894 solventless oxidation to disulfides, 1497 with acyl halides, 1201, 1211 with alkenes, 894, 1006 with alkyl halides, 476 with alkynes, 894 with alkynes, metal catalyzed, 895 with alkynes, photochemical, 894 with amines and alkenes, 1012 with carboxylic acids, 1206, 1211 with hydrogen peroxide, 1496 with ketenes, 895 with LiAlH4, 1551 with norbornene, 1334 with phosphoric acid esters, 1211 with triflic acid, 1206 with vinyl ethers, 894 thionitrites, and conversion of anilines to aryl halides, 847 thiono esters, catalytic hydrogenation, 851 thionocarbonates, and the CoreyWinter reaction, 1301 cyclic, cleavage to alkenes, 1301 from diols and thiophosgene, 1301 thionoesters, reduction to ethers, 1543 thionolactones, formation of cyclic ethers, and organolithium reagents, 1133 thionyl chloride, 500 and dehydration of amides to nitriles, 1313 and the Sni mechanism, 409 formation of aryl sulfoxides, 602 with alcohols, 409 with alkylsulfinic acids, 856 with carboxylate anions, 1210 with carboxylic acids, 1224 with sulfinic acids, 1251 thiophenes, and aromaticity, 57, 58 and Friedel-Crafts acylation, 623 and Friedel-Crafts alkylation, 611 arylation, 755 by metal catalyzed addition of thiols to alkenes, 895 desulfurization, 852, 1551 desulfurization, to alkenes, 852 electrophilic aromatic substitution, 584 halogenation, 607, 703 metal catalyzed coupling with aryl halides, 760 reduction, 1551 resonance energy, 58 thiophenols, formation of thioethers, 750 from aryldiazonium salts, 791 organolithium reagents, conjugate addition, 968 with alkenes, 894 thiophilic addition, 1067 thiophosgene, with amines, 1214 with diols, 1301 with DMAP and diols, 1302 thiosulfate ion, with alkyl halides, 479 thioureas, and alkenes, metal catalyzed formation of thiiranes, 1006 and E/Z isomerization of conjugated aldehydes, 882 and inclusion compounds, 114 chiral, 1103 formation of thioethers, 477 from isothiocyanates and amines, 1103 with alkyl halides, 476 thio-Wittig see Wittig thorium oxide, and decarboxylation of carboxylic acids, 1238 and dehydration of alcohols, 1283 Thorpe condensation, 1142 Thorpe reaction, 1179 intramolecular, 1179 Thorpe-Ziegler reaction, 1179 threads, molecular, 118 three-center hydrogen bond, 99 threo nomenclature, 148 thujones, 815 Ti catalyst, acyl addition, 1120 and epoxidation, 1004 diamination of alkenes, 1008 imino esters with aldehydes, 541 Ti complex, and acyl addition, 1118 Ti compounds see organotitanium Ti, low valent, 1556 TiCl3 and LiAlH4, coupling alcohols, 532 TiCl4, rearrangement of epoxy alcohols, 1344 Tiffeneau-Demyanov ring expansion, 1346 SUBJECT INDEX tight ion pair, 384 tight ion pair, and Friedel-Crafts alkylation, 614 tiglic acids, 657 tin compounds see organotin tin hydrides see hydrides tin, see organotin tin, acyl see acylation tin, allylic, acyl addition, 1119 compounds, acyl addition, in ionic liquids, 1118 with aldehydes or ketones, 1118 with transition metal catalysts, 1118 tin, propargylic, 1118 Tischenko reaction, 1564 and aldol reaction, 1564 and hydroformylation, 979 catalysts, 1564 crossed, 1564 Tischenko-aldol transfer reaction, 1565 titanium cyclopentadienidedimethylaluminum complex see Tebbe’s reagent titanium mediated coupling of aldehydes or ketones, 1558 titanium pinacoloate, 1560 titanium tetrachloride chiral amides with aldehydes, 1120 titanium tetraisopropoxide, and Sharpless asymmetric epoxidation, 1004 titanium, coupling of dialdehydes, 1557 low valent, 1306, 1559 titanocene dichloride, and reduction of esters, 1546 titanocene, dimethyl, 1174 TMEDA, and organolithium reagents, 231, 232, 1110 TMEDA-butyllithium, 784 tolanes also see alkynes tolanes, by oxidative coupling of dihalotoluenes, 1495 Tollen’s condensation, 1562 and the Cannizzaro reaction, 1563 and the crossed Cannizzaro reaction, 1563 Tollen’s reaction, 1142, 1164 and crossed Cannizzaro reaction, 1164 and mixed aldol reaction, 1164 toluene, as a solvent, 714 dipole moment, 18 electrophilic aromatic substitution, 588 reaction parameters, 589 tolylnapthalenes, and strain, 206 topological polarization, 65 topological stereoisomers, and catenanes, 119 tormented aromatic compounds, 48 torquoselectivity, 1381 torsion angle also see angle torsion angle, and specific rotation, 125 and keto-enol tautomerism, 666 and molecular mechanics, 191 torsional barrier, of amides, 179 of carbamates, 180 torsional diastereomers, 132 ToSMIC, amide formation, 495 tosyl aziridines, 990 tosylamines, conversion to alkyl halides, 509 halo, 989 with epoxides, 490 tosylates also see sulfonate esters tosylates, acetyl, formation of carboxylic esters, 471 alkyl, rate of SN1, 420 and solvolysis, 385 decomposition to alkenes, 1289 leaving groups, 432, 433 reduction to methyl compounds, reagents for, 1537 solvolysis, 395 tosylazides see azides tosylazides, with active methylene compounds, 678 tosylaziridines, from epoxides, 490 with alkenes, 1011 tosylcyanide, 563 tosylcyanide see cyanides tosylhydrazine, formation of allenes, 664 tosylhydrazones see hydrazones O-tosyl imines, and the Neber rearrangement, 1359 tosylimines see imines, tosyl tosylisocyanides, Knoevenagel reaction, 1159 toxicity, of cyclodextrins, 117 TPAP (tetrapropyl perruthenate), oxidation of alcohols, 1446 and oxidation of amines, 1483 and oxidation of thioethers, 1494 catalytic oxidations, 1446 polymer-bound, 1446 recovery of catalysts, 1446 the Ley reagent, 1446 transacetalization, 1083 transamidation, 1212 and the zip reaction, 1222 and thioamides, 1212 transamination, 487 transannular hydride shift, 1428 transannular hydrogen atom shifts, 1336 2039 transannular interactions, 200 transannular rearrangements, 1332 and alkyl groups, 1333 transannular shifts, of hydrogen atoms, 1336 transannular strain, 199 transannular strain also see strain trans-cis isomers, 167 transesterification, 1206 and boiling point, 1206 and enol esters, 1208 and lipases, 1207 and polymer bound siloxanes, 1207 and superbases, 1207 and vinyl acetate, 1207 enzymatic, 1207 in ionic liquids, 1207 Lewis acid catalysts, 1207 mechanism, 1207 metal mediated, 1208 of lactones, 1207 regioselectivity, 1207 thioesters, 1207 transetherification, 464 and acetals, 465 and enol ethers, 465 and ortho esters, 465 internal, 464 transfer hydrogenation, 910, 912, 1510, 1513 and Hantzch esters, 917 and organocatalysts, 917 transformation, IUPAC nomenclature, 368 transient grating spectroscopy, and carbenes, 254 transition energies, 441 transition metal catalysts, and Friedel-Crafts acylation, 622 diazonium salts, 788 transition metal complexes, 786 transition metals, chiral catalysts, 1153 chiral complexes, 1148 transition state geometry, aldol reaction, 1145 and rate of SN2, 420 transition state, 265 ab initio study, radical hydrogen abstraction, 812 aldol reaction, 1145 amide hydrolysis, 348 and activation volume, 362 and calculations, 35 and ester hydrolysis, 1196 and H abstraction by radicals, 812 and high pressure, 362, 446 and intermediates, 270 and proton transfer, 329 and solvent polarity, 435, 437 2040 SUBJECT INDEX transition state (Continued ) and the Hammond postulate, 418 aryl migration, 1335 carbocations, and elimination, 1274 transition state, cyclic, and Meerwein-Ponndorf-Verley reduction, 1507 elimination, 1278 lead tetraacetate cleavage of diols, 1457 oxidative cleavage of diols, 1457 transition state, dipolar, and high pressure, 446 E2 reaction, 1269 E2C mechanism, 1268 E2C reactions, 1269 Ei reactions, 1280 elimination of epoxides with phosphines, 1286 epoxidation of alkenes, 999 for [2ỵ2]-cycloadditions, 1033 for [4ỵ2]-cycloadditions, 1033 for Grignard reactions, 1112 for the Barton reaction, 1427, 1428 for the Claisen rearrangement, 1407 for the Cope rearrangement, 1403, 1404 for the Diels-Alder reaction, 1024 for the Meerwein-PonndorfVerley reduction, 1508 imaginary, for [1,3]-sigmatropic rearrangement, 1392, 1393 ionic, and polar solvents, 435 lifetimes, 272 nucleophilic substitution at sulfonyl sulfur, 1248 peroxyacid epoxidation of alkenes, 999 polarized, 378 pyrolysis of keto-ylids, 1293 pyrolytic elimination, 1278 radical abstraction, 808 radical formation, 808 radicals, 816 six-center, 1428 six-center, and Diels-Alder reactions, 869 SN2 character, 449 SN2, 377, 418 SN2, and neopentyl systems, 651 substitution reactions, 437 syn elimination, 1269 tight, and SN2 reactions, 422 transitional isomers, rotaxanes, 118 transitions, in photochemistry, 292 transitions, in photochemistry also see photochemistry transition-state theory, 267 transmetallation, and carbanion stability, 712 and higher order cuprates, 712 and metallocenes, 711 and organocuprate formation, 711 and organolithium reagents, 712 electromotive series, 710 Pd catalysts, 773 with metal halides, 710 with metals, 710 with organometallics, 712 transoid dienes, in the Diels-Alder reaction, 1021 trans-Pd complex, 683 trans-thiiration, 1006 trapping intermediates, 276 tresylates, leaving groups, 432, 433 triacylamines, 1214 trialkoxysilanes, with aryl halides, 783 trialkylaluminums, 533 trialkylboranes see boranes trialkylfluoroborates, coupling reactions, Pd catalyzed, 560 from boronic acids, 560 stability, 560 triarylamines, and chirality, 135 triarylmethyl carbocations, 217 triazenes, 728 and azides, 707 aryl, isomerization, 597 aryl, rearrangement, 639 cis-trans isomerization, 882 with aromatic compounds, 795 with HF, 792 by trimerization of nitriles, 1240 triazoles, and amination, 787 from azides, 1018 triazolines, by [3ỵ2]cycloaddition, 1017 by 1,3-dipolar addition of alkyl azides, 1009, 1010 extrusion of nitrogen, 1316, 1317 from alkyl azides and alkenes, 1009, 1010 photolysis, 1009, 1010, 1017 thermolysis, 1009, 1010 tribromides, and bromination of alkenes, 983 tributyltin chloride, with alkyneboranes, 1379 tributyltin dimer, and radical cyclization, 961, 962 tributyltin hydride also see hydride and radical cyclization, 961 and reduction of conjugated esters, 918 and sulfoxide elimination, 1296 preparation, 959 reduction of isocyanides, 1548 with AIBN, 1296 tributyltin oxide, with vinyl halides, 452 tricarbonates, with amines, 731 tricarboxylates, aryllead, arylation of aromatic compounds, 844 trications, 213 trichloroacetimidates, and azaClaisen rearrangement, 1411 trichloroacetonitrile, with aromatic compounds, 633 trichloroamine, and amination of aromatic compounds, 599 with alkanes, 491 trichloroisocyanuric acid, and conversion of aldehydes to nitriles, 1096 and N-haloamines, 730 and PPh3 with alcohols, 501 chlorination of alkynes, 706 with alkenes, 884 with carboxylic acids, 1216 tricyclododecadiene, 206 trienes, and cross conjugation, 42, 43 and interconversion with cyclohexadiene, 1402 and orbitals, 42 and the valence bond method, 43 by cheletropic reactions, 1303 cyclohexadiene interconversion, orbital requirements, 1384, 1385 from cyclic dienes, 1380 from thiepin-1,1-dioxides, 1303 hydroboration, 925, 1376 thermal ring closure to cyclic dienes, 1380 triethylamine, and Grignard reagents, 231 triethylborane, and radicals, 960, 964 radical initiator, 960 triethylborohydride, lithium, 915 with ammonium salts, 1548 triflates, aryl, and Suzuki-Miyaura coupling, 770 coupling with phenols, 460 coupling with trialkylfluoroborates, 560 formation of aryl nitriles, 633 from aryldiazonium salts, 791 leaving groups, 432, 433 vinyl, and palladium catalyst, 461 vinyl, and Stille coupling, 682 vinyl, with LiCN, 563 SUBJECT INDEX vinyl, with vinyltin reagents, 682 with amines, 751 with trifluoroborates, 890 triflic acid, with thiols, 1206 triflic anhydride see anhydride with amides, 1208 triflimide, as an acid, 888 trifluoride ions, 1106 trifluorides, from carboxylic esters, 1106 trifluoroacetic anhydride, 1084 trifluoroacetic anhydride see anhydrides trifluoroarylboronates, with amines, 754 trifluoroborates, alkene, Pd catalyzed coupling, 843 alkyl, with aryl halides, 768 alkyne, Pd catalyzed coupling, 843 alkynyl, 778 and Sonogashira coupling, 778 aryl, and Suzuki-Miyaura coupling, 775 aryl, conjugate addition, 958 aryl, with aryldiazonium salts, 794 formation of boronic acids, 701 potassium, from KHF2, 703 potassium, stability of, 703 vinyl, and the Heck reaction, 768 vinyl, with aryl halides, 768 trifluoroborates, with alcohols, 462 with aldehydes, 1125 with aryl halides, 775, 890 with aryl sulfonate esters, 890 with aryliodonium salts, 890 with imines, 1136 trifluoromethanesulfonate esters, 1083 trifluoromethanesulfonic acid see triflic acid with aryldiazonium salts, 791 trifluoromethanesulfonic anhydride, VilsmeierHaack reaction, 626 trifluoroperoxyacetic acid, 830 trigonal hybridization, trihalides, formation of esters, 452 from CCl4 and alkenes, 452 hydrolysis of, 452 trihomoaromatic, 83 trihomobarrelyl carbocations, 217 triiodide, and iodination of aryldiazonium salts, 792 triketones, cyclotrimerization, 1061 from diketone dianions, 1237 nitrogen fixation, 1061 trimerization, of aldehydes, 1240 of alkynes, 1059 spontaneous, 1059 trimethylaluminum, metalation of tertiary alcohols, 533 trimethylamine N-oxide, 15, 16 trimethylamine oxide, oxidation of boranes, 701 trimethylenemethane radicals, 245 trimethylenemethane, [3ỵ2]cycloaddition, 1019 with alkenes, 1019 trimethyloxonium salts, 1209 trimethylsilyl amides, and nitrile formation, 1096 trimethylsilyl chloride, trapping acyloins, 1561 trimethylsilyl cyanide see cyanide trimethylsilyl cyanide, 564 with alkyl halides, 563 trimethylsilyl halides, and acyloin condensation, 1561 2-[(trimethylsilyl)methyl]-2propen-1-yl acetate, 1019 trinitrobenzenes, and complex formation, 107 trioxane, and cross coupling of alkanes, 840 from formaldehyde, 1240 trioxolanes, and ozonolysis, 1460 from aldehydes, 1240 hydrolysis, 1461 ozonides, 1460, 1461 triphase catalysts, 445 triphenylenes, 57, 85 and aromaticity, 57 and electron distribution, 57 solubility, 57 triphenylmethyl carbanion, 223 triphenylmethyl carbocation, 213, 217 triphenylmethyl radical, 238 canonical forms, 238 stability, 819 triphenylphosphine oxide, by oxidation of triphenylphosphine, 1492 triphenylphosphine, and dehydration of alkynealcohols, 1284 and phosphorus ylids, 1168– 1173 and tetracarbonylferrate, 564 elimination with epoxides, 1286 oxidation to triphenylphosphine oxide, 1492 reduction of amine oxides, 1549 reduction of azoxy compounds, 1549 scavenging by Merrifield resin, 777 with alcohols and carbon tetrachloride, 502 with allylic alcohols and carbon tetrachloride, 503 with carbon tetrachloride, and carboxylic acids, 1224 2041 triple bonds, and delocalization, 37 conjugated with p orbitals, 39 triple metathesis, 1421 triple-decker sandwiches, 61 triplet carbenes also see carbenes triplet carbenes, 250, 257, 1055 persistent, 251 triplet carbonyls, 1243 triplet nitrenes, 258, 1010 triplet nitrenium ions, 260 triplet oxygen, with alkenes, 833, 834 triplet radicals, 245 triplet sensitizers, 972 triplet state, [2ỵ2]-cycloaddition, 1049 photochemistry, 1049 triplets, in photochemistry, 292, 295 tris(trimethylsilyl)silane, 960, 964 and radical cyclization, 963 tri-sec-butylborohydride see Selectride tri-tert-butylcyclobutadiene, and valence tautomerism, 1406 tritiation, aromatic compounds, 593 tritium labeling, 416 and diradicals, rearrangements, 1335 tritium, isotope effects, 286 tritium-decay, for generation carbocations, 416 tritium-hydrogen exchange, 660 trityl carbocations, 213 triynes, cyclotrimerization, 1060–1062 Tr€oger’s base, and chirality, 129 tropane, 79 tropolones, and NMR, 60 and X-ray, 60 aromatic character, 60 bond alternation, 60 tropones, and cyclopropenyl cations, 67 and NMR, 60 and X-ray, 60 aromatic character, 60 bond alternation, 60 stability, 67 tropylium bromide, 60 tropylium ion, and aromaticity, 62 and Friedel-Crafts alkylation, 614 formation and stability, 60 Truce-Smiles rearrangement, 802 truxilic acid, and chirality, 125 Tsuji-Trost reaction, 528 tub conformation, 134 cyclooctatetraene, 134 tungsten reagents, deoxygenation of diols, 1301 2042 SUBJECT INDEX twist conformation, 181 azaannulenes, 74 annulenes, 72 twistane, and twist conformation, 182 twisted amide bonds, and hydrolysis, 1197 twisted amides, 199 twisted aromatic compounds, 48 twisted aromatics, 48 twisted carbocations, 1331 twisted compounds, 199 twisted Diels-Alder reaction, 1035 twisted double bonds, 206 twisting, and chirality, 133 Udenfriend’s reagent, hydroxylation of aromatic compounds, 830 Ugi four-component reaction, 1247 Ugi reaction, 1247 and imines, 1247 isocyanide free, 1247 Ugi three-component reaction, 1247 Ullmann biaryl synthesis, 748 Ullmann coupling, heterocyclic compounds, 769 Ullmann ether synthesis, 748 Ullmann reaction, 514, 768 alternatives, 769 and microwaves, 311 and the Wurtz reaction, 769 asymmetric, 769 mechanism, 769 ultracentrifuge, and Diels Alder reactions, 1023 ultrasonic waves, and acoustic cavitation, 307 and sonochemistry, 307 ultrasound also see cavitation ultrasound also see sonication ultrasound also see sonochemistry ultrasound, 307–309 ultrasound, alkylation and alkyl halides, 445 and acyl cyanides, 1238 and acylation of carboxylic acids, 1209 and aromatic halogenation, 604 and carbene generation, 691 and carbene insertion, 692 and cavitation, 445 and DDQ, oxidation of alcohols, 1452 and Diels Alder reactions, 1022 and dihydroxylation, 994 and heteroatom Diels-Alder reactions, 1038 and hydrolysis of carboxylic esters, 1192 and lactonization, 1013 and liquids, 307 and lithium, 1232 and Michael reactions, 947 and a-oxidation of ketones to diketones, 1477 and permanganate oxidation of alcohols, 1445 and radicals, 445 and reactivity, 445 and reduction of nitro compounds, 1524 and SRN1 reactions, 740 and the acyloin condensation, 1561 and the Baylis-Hillman reaction, 1127 and the Knoevenagel reaction, 1158 and the Pauson-Khand reaction, 977 and the Reformatsky reaction, 1129 and thiocyanates, 480 and zinc, 1129 aryl halides with amines, 751 formation of alkyl azides, 496 halogenation of aromatic compounds, 604 lactonization of alkenes, 1013 metals and pinacol coupling, 1556 pulsed, 308 with potassium permanganate, dihydroxylation, 994 ultraviolet see UV Umpolung, acyl anion equivalent, 549 and aldehydes, 553 and dithianes, 553 and sulfoxides, 553 definition, 549 unavoidable strain, 183 ungerade orbitals, unimolecular substitution see substitution, SN1 universal NMR database, and absolute configuration, 143, 144 unshared electrons, and nucleophilicity, 430 unsolvated aryllithium reagents, 232 unsymmetrical coupling see coupling ppfield shift, 51, 68 uranium complex, alkynes with isonitriles, 1141 urea complex, 113 urea, 114 and cage structures, 155 and Fischer-Hepp rearrangement, 639 and guest-host interactions, 113 arylation, 755 as a guest, 113 as an inclusion compounds, 113 carbonylation of amines, 730 with acyl halides, 1223 urea-hydrogen peroxide, 1003 and epoxidation, 1003 in formic acid, oxidizing agent, 1492 ureas, and the Baylis-Hillman reaction, 1128 and the Hoffmann rearrangement, 1360 by carbonylation of amines, 730 by the Ritter reaction with cyanamides, 1240 dehydration reagents, 1314 dehydration to carbodiimides, 1314 dehydration to cyanides, 1313 dehydration, 1314 diazotization, 790 from addition of amines to carbon dioxide, 1105 from amines and carbon dioxide, 731 from dicarboxylic esters, with urea, 1223 from isocyanates and amines, 1103 with dienes, 1009 urethanes, substituted see carbamates UV (ultraviolet), 1583 absorption peak, 291 addition of halogens to cyclopropanes, 881 alkenes with haloamines, 988 and addition of aldehydes to alkenes, 971 and addition of sulfonyl halides to alkenes, 988 and addition reactions of alkynes, 873 and annellation, 57 and asymmetric synthesis, 151 and auxochromes, 293 and bromine or chlorine, 982 and carbanions, 662 and conformations, 174 and cyclopropane, 195 and detection of carbocations, 382 and dimerization of ketones, 1557 and EDA complexes, 105 and electrocyclic reactions of stilbenes, 1390 and electrocyclic ring opening, 1380 and enolate anion formation, 778 and halogenation of alkanes, 821 and halogenation of alkenes, 982 SUBJECT INDEX and halogenation, 826 and hyperconjugation, 85 and methane, 11 and nitrosation, 676 and nitrosyl halide, 676 and photochemistry, 290, 293 and pK, 339 and polyhalo addition to alkenes, 991 and quinone substitution, 414 and radicals, 238 and reactions, 151 and strained aromatic compounds, 204 and substitution at vinyl carbon, 414 and the Fries rearrangement, 637 arylation of active methylene compounds, 778 nitriles and alkanes, 838 reduction of nitro compounds, 1526 UV, dienes, 293 far UV, 293 far UV, and photochemistry, 290 isotropic, 143 paracyclophanes, 47 polyenes, 293 substituted benzenes, table, 294 valence bond isomers, 166 valence bond method, 4, and trienes, 43 valence bond order, 915 valence bond theory, and benzene, 35 valence electrons, 14 valence isomers, 1051 valence isomers also see isomers valence tautomerism, and Cope rearrangement, 1404 cycloheptatrienes-norcaradiene, 1406 oxepin-benzene oxide, 1406 tri-tert-butylcyclobutene, 1406 valence, and electronic structure, 15 multiple, of boron, valence-bond bond order, and principle of least motion, 915 van der Waals forces, 96 and guest-host interactions, 113 and inclusion compounds, 113 and molecular mechanics, 190, 191 van der Waals radii, and Charton’s n values, 360 vanadium complexes, 41 very fast reactions, kinetics, 282 very weak acids, 319 vibrational circular dichroism, 143 vibrational levels, and photochemistry, 295 vicarious nucleophilic substitution of hydrogen, 786 vic-diiodides, stability, 982 Vilsmeier reaction, aliphatic, 685 and haloacylation of alkenes, 992 formation of keto-aldehydes, 685 Vilsmeier-Haack reaction, 625 Vilsmeier-Haack reaction, and Beckmann rearrangement, 626 and microwave irradiation, 626 sulfonic anhydrides, 626 mechanism, 626 vinamidine proton sponges see proton sponge vinamidine proton sponges, 322 vinyl acetate, and transesterification, 1207 vinyl alcohol, 91 vinyl boranes see boranes vinyl boranes see boranes, alkenyl vinyl carbanions, and configurational stability, 228 vinyl carbenes, 252 vinyl carbocations, 215 vinyl carbocations see carbocations vinyl carbons, retention of configuration, 227 vinyl chloride, 171 orbitals, 40 vinyl compounds, and nucleophilic substitution, 419 and SE1 reactions, 656 hydrolysis, 453 vinyl cyanides see cyanides from vinyl bromides, 563 vinyl esters, from vinyl halides, 469 from vinyliodonium salts, 703 vinyl ethers, deprotonation of, 696 vinyl halides see halides, vinyl vinyl halides, formation of vinyl esters, 469 formation of vinyl sulfides, 477 vinyl iodonium salts, with sodium sulfonate, 480 vinyl organometallics, and Stille coupling, 682 formation of dienes, 682 vinyl phosphates, 704 vinyl phosphines, Markovnikov addition, 899 vinyl radicals see radicals vinyl silanes, 705 vinyl silanes see silanes vinyl substrates, Suzuki-Miyaura coupling, 771 2043 vinyl sulfides see sulfides vinyl sulfides, from vinyl halides, 477 vinyl sulfones, from vinyl iodonium salts, 480 vinyl triflates see triflates vinylation, of ketones, 545 vinylboranes, from alkynylboranes and alkylating agents, 1380 vinylcyclobutanes, rearrangement to cyclohexenes, 1399 vinylcyclopropane rearrangement, 1399 and cleavage of cyclopropane, 1399 and homodienyl [1,5]-shift, 1399 heteroatom, 1399 mechanism, 1400 vinylcyclopropanes, by carbene addition to dienes, 1053 from dienes, 1425 sigmatropic rearrangement, 1398 with acids HX, 884 vinylhalonium ions, 214 vinylic carbocations, 865 vinylic carbon, additionelimination mechanism, 413 and SN1 reactions, 415 nucleophilic substitution, 413 vinylic compounds, and SN1 reactions, 419 elimination-addition mechanism, 416 vinyllithium reagents, by deprotonation, 696 with silyl peroxides, 700 vinylogous chiral aldol reactions, 1148 vinylogous conjugate addition, 944 vinylogous Mannich reactions, 1101 vinylogous Michael reactions, 944 vinylogous Nazarov cyclization, 946 vinylogy, and enolate anions, 549 and the aldol reaction, 1143, 1144 and the E2 reaction, 1258 enantioselective aldol reactions, 1148 vinylsilanes see silanes vinyltellurium with alkynes, 939 vinyltin reagents, with vinyl triflates, 682 visible absorption peak, 291 visible spectrum, 143 Vitride, 1502 Vocabulary of Organic Chemistry, 1591 2044 SUBJECT INDEX volume of activation, and high pressure, 446 volume, activation see activation volume von Braun reaction, 509, 1313 mechanism, 510 counterattack reagent, 510 von Richter reaction, 745 and mechanism, 275 mechanism, 276 von Richter rearrangement, 797 and labeling, 798 mechanism, 798 N2 leaving group, 797 Wacker process, 1488 and Markovnikov’s rule, 1488 aza-, 1489 mechanism, 1488 Wadsworth-Emmons see WittigHorner Wagner-Meerwein rearrangements, 1338– 1342, 1368 and 3,2-shifts, 1339 and alkanes, 1341 and elimination, 1339 and equilibrium, 1341 and friedelin, 1340 and Nametkin rearrangement, 1340 and Nazarov cyclization, 947 and nonclassical carbocations, 1340 and oleanene, 1340 and retropinacol rearrangement, 1340 and Zaitsev’s rule, 1338 catalytic, 1340 enantioselectivity, 1340 hydride shifts, 1339 isotopic labeling, 1341 leaving groups, 1339 mechanism, 1341 migratory aptitudes, 1328 stereoselectivity, 1341 Waits-Scheffer epoxidation, 1003 mechanism, 1003 Walden inversion, and hydride reduction of alkyl halides, 1534 and mechanism, 278 in SN2 reactions, 375 Wallach reaction, 1098 and the Leuckart reaction, 1098 with formamides, 1098 Wallach rearrangement, 1429, 1562 and isotopic labeling, 1430 and para rearrangement, 1430 mechanism, 1430 photochemical, 1430 warming, and microwaves, 310 water promoted amide hydrolysis, 1197 water promoted Michael reactions, 945 water, acyl addition to carbonyls, 1075 acyl addition, 1076 addition to carbonyls, mechanism, 1076 and acceleration of the Claisen rearrangement, 1408 and alkyl, halides, 451 and cage compounds, 114 and carbon monoxide, with alkenes, 972 and Diels Alder reactions, 363, 1023 and Hofmann elimination, 1291 and phase transfer catalysis, 443 and reactivity, 363 and the Mukaiyama aldol, 1152 water, angular, as a solvent, 1408 basicity of amines, 320 bond angles, catalysts, for sulfonation of alkenes, 893 heteroatom Diels-Alder reactions, 1038 labeling, 798 supercritical, and Diels Alder reactions, 1023 supercritical, as a solvent, 1342 water, with acyl halides, 1189 with alkynes, 887 with amine halides, 1356 with aziridinium salts, 1357 with azirines, 1359 with carbocations, 1184 with chlorine, 985 with Grignard reagents, 714 with isocyanates, 1362, 1363 with isocyanides, 1246 with ketenes, 1353 wave equations, and resonance, 32 wave function, wave mechanical calculations, wave mechanics, wavelength of light, and bond energy, 295 and conjugation, 293 and microwave irradiation, 310 and photochemical [2ỵ2]cycloaddition, 1048 and photochemistry, 290 and photolysis of dienes, 1380 and specific rotation, 125, 143 weak hydrogen bonding, 102 weak interactions, 123 Web of Science, 1575 weighting factor, and wave equations, Weinreb amides, 1147 and the Wittig reaction, 1167 from carboxylic acids, 1216 intramolecular displacement, 1230 preparation, 1217 reduction to aldehydes, 1520 with Grignard reagents, 1230 with organolithium reagents, 1230 Weissler reaction, and sonochemistry, 309 Weitz-Scheffer epoxidation, 1000 Wheland intermediates, 570 Whitmore 1,2-shifts, 1322 Wigner spin-conservation rule, 300 and photochemical [2ỵ2]cycloaddition, 1049 Wilkinsons catalyst, 41 and decarbonylation of aldehydes, 856, 857 and enantioselectivity in catalytic hydrogenation, 904 and hydroboration, 926 and hydrogenation, 903 decarbonylation mechanism, 858 mechanism of homogenous hydrogenation, 908 Willgerodt reaction, 1566 and Montmorillonite, 1567 Kindler modification, 1566 Willgerodt rearrangement, 1338 Williamson ether synthesis see Williamson reaction Williamson ether synthesis, an SN2 reaction, 461 Williamson reaction, 459 and epoxides, 461 and ionic liquids, 459 and micellar catalysis, 460 and microwave irradiation, 459 and the Mitsunobu reaction, 460 and phase transfer catalysis, 460 and SET mechanism, 461 and thioether formation, 476 Wittig reaction, 1142, 1165–1173 and amides, 199 and arsine ylids, 1169 and azaadamantanone, 199 and betaines, 1168 and epoxides, 490 and Michael alkenes, 1165 and NMR, 1168, 1169 and oxaphosphetanes, 1168 and Peterson alkeneylation reaction, 1162 and Reformatsky reaction, 1130 and scoopy reactions, 1172 and synthesis, 1172 and the Knoevenagel reaction, 1159, 1160 SUBJECT INDEX betaine-lithium halide intermediate, 1172 compatible functional groups, 1166 E/Z-selectivity, 1171 energetics of ylid formation, 1168 E-selectivity, 1171 formation of anti-Bredt alkenes, 1168 formation of exocyclic alkenes, 1167 in aqueous media, 1166 intramolecular, 1172 mechanism, 1168 on silica gel, 1166 structural requirements of the carbonyl, 1166 with Weinreb amides, 1167 Z-selectivity, 1171 Wittig reagents see ylids, phosphorus Wittig rearrangement, 555, 1373, 1414 formation of ketyls, 1374 mechanism, 1374 migratory aptitudes, 1374 stereospecificity, 1374 with vinyl ethers, 1374 [2,3]-Wittig rearrangement, 1413 and chirality transfer, 1414 and deformation of the molecule, 1413 enantioselectivity, 1414 structural requirements, 1414 structural variations, 1414 Wittig type reactions, and Grignard reactions, 1109 Wittig, aza- also see aza-Wittig Wittig, thio-, 1168 Wittig-Horner reaction, 1169 electronic effects on the ylid, 1169 intramolecular, 1170 stereoselectivity, 1170 Wohl-Ziegler bromination, 821, 826 Wolff rearrangement, 256, 1244, 1353 and diazoketones, 1244 and the Arndt-Eistert synthesis, 1353 formation of ketones, 1353 isotopic labeling, 1354 mechanism, 1353 photochemical, 1354 Wolff-Kishner reduction, 1540, 1547 and semicarbazones, 1540 carbanion intermediates, 1542 Huang-Minlon modification, 1540 mechanism, 1542 Woodward modification, of the Prevost reaction, 994 Woodward-Hoffmann rules, 1030, 1064 and metal catalyzed cycloadditions, 1064 and photochemical [2ỵ2]cycloaddition, 1050 and Ei reactions, 1280 and electrocyclic reactions, 1388 “wrong way” rearrangements, 1336 Wurtz coupling, 520, 713 and organolithium reagents, 716 different metals, 515 of conjugated ketones, 514 solvent effects, 515 Wurtz reaction, 513, 769 and allylic rearrangement, 514 and coupling of acyl halides, 1232 and Grignard reagents, 849 and the Ullmann reaction, 769 cyclization, 513, 514 formation of bicyclic compounds, 514 intramolecular, 514 mechanism, 514 Wurtz type coupling, and Grignard reactions, 1111 Wurtz-Fittig reaction, 513 xanthate esters see esters xanthates, and the Chugaev reaction, 1289 from alcohols and carbon disulfide, 1086 pyrolysis to alkenes, 1288 xanthine dye, photosensitizer, 1039 X-ray crystallography, and hydrogen bonds, 99 and annulenes, 75, 80 and Bijvoet, 139, 142 and bond distance, 23 and carbanions, 224 and carbenes, 255 and conformations, 174, 178 and cyclobutadiene complexes, 69 and D/L nomenclature, 138, 142 and diastereomers, 148 and enolate anions, 232 and homoazulenes, 74, 75 and hydrogen bonds, 99 and hyperconjugation, 87 and isopropyllithium, 231 and LDA, 341 and Meisenheimer salts, 733 and organolithium reagents, 231, 232 and osmium tetroxidediamination, 1009 2045 and Simmons-Smith intermediates, 1057 and twisted alkenes, 206 biphenylenes, 48 tert-butyl carbocation, 211 cyclobutadienes, 69 intermediate of the Reformatsky reaction, 1130 methyllithium, 229 nitronium ions, 595 nitroxyl radicals, 241 of the methyl carbocation, 209 osmium catalyst, 1054 oxonium ion, 219 propellanes, 198 X-ray diffraction, and bond distance, 21 and Grignard reagents, 230 and paracyclophanes, 46 and strain in medium rings, 199 pentalene derivatives, 63 tropones and tropolones, 60 X-ray electron spectroscopy, and nonclassical carbocations, 404 X-ray photoelectron spectroscopy see ESCA X-ray structure, of betaines, 1168 Yamaguchi protocol, 1204 Y-aromaticity, 38 Yb, amines with oxetanes, 490 ylid formation, energetics, 1168 ylid reactions, solvent effects, 1171 ylid, dimethyloxosulfonium methylid, with aromatic nitro compounds, 786 ylides, see ylids ylids, and acyl addition, 1179 and bonding, 49 and carbene insertion, 693 and carbenes, 693 and field effects, 225 and Hofmann degradation, 1290 and orbitals, 49 and resonance, 49 and sulfuric acid, 49 ylids, arsine, 1169 arsonium, with tosylimines, 1177 as intermediates, 1292 carbonyl, [3ỵ2]-cycloaddition, 1015 dimerization, 1173 dimethyloxosulfonium methylid, 1175 dimethylsulfonium methylid, 1175 in the Steven’s rearrangement, 1372 nitrile, in [3ỵ2]-cycloadditions, 1015 2046 SUBJECT INDEX ylids, nitrogen, 50, 1173 and field effects, 225 and organolithium reagents, 697 formation of alkenes, 1292 from ammonium salts, 697, 1292 ylids, oxido phosphorous, 1172 ylids, phosphine oxide, 1171 ylids, phosphonate, 1169 and Wittig-Horner reaction, 1169 electronic effects, 1169 ylids, phosphonium, 697 ylids, phosphorus, acyl, pyrolysis to alkynes, 1293 alkoxy, 1171 alkoxy, and scoopy reactions, 1172 and [2ỵ2]-cycloadditions, 1171 and resonance, 1165 and triphenylphosphine, 1168– 1173 from phosphonium salts and base, 1165 functional group capability, 1167 in the Wittig reaction, 1165 reactions with functional groups, 1173 reactivity with aldehydes and ketones, 1167 salt free, 1165 stability and reactivity, 1167 stabilized, 1167, 1170 structural requirements, 1167 suitable bases for formation of ylids, 1165 versus sulfur, 1177 with aldehydes or ketones, 1165 with carbon dioxide, 1173 ylids, polymer supported, in the Wittig reaction, 1166 reaction with alcohols and an oxidizing agent, 1166 reactivity, 1169 selenium, 50 selenium, and formation of epoxides, 1176 selenium, chiral, 1176 structural types, 1169 sulfonium, 1176 sulfoxonium, 1176 ylids, sulfur, 50, 799 and [2,3]-sigmatropic rearrangements, 1413 and formation of cyclopropanes, 1176 and sigmatropic rearrangements, 799 and Stevens’ rearrangement, 1373 and the Sommelet-Hauser rearrangement, 799 chiral, 1176 diastereoselectivity, 1176 epoxide formation, enantioselectivity, 1176 in ionic liquids, 1178 kinetic versus thermodynamic control, 1176 polymer-supported, 1176 reaction with epoxides, 1176 rearrangement, 799 solvent free, 1176 with aldehydes or ketones, 1175–1177 with allylic alcohols, 1179 with conjugated compounds, 1178 with epoxides, 1287 ylids, tellurium, 1169, 1177 with imines, 1177 ylids, thiocarbonyl, in [3ỵ2]cycloadditions, 1016 ylids, with aldehydes or ketones, 1165–1173 with carbon dioxide, 1173 with lactams, 1166 with lactones, 1166 ynamides, 777 ynamines also see alkyne amines ynamines, hydration of, 888 yn-dienes, and the Pauson-Khand reaction, 976 ynolates, with dienes, 1232 ynones, addition of silyl phosphines, 930 with silylphosphines, 930 Z/E nomenclature, definition, 163 Zahlenwerte und Funktionen aus Physik, Chemie, Astronomie, Geophysik, und Technik, 1581 Zaitsev orientation, and thermodynamic alkene, 1271 Zaitsev products, elimination, 1281 Zaitsev’s rule, and alkene stability, 1270 and carbocations, 1339 and dehydration of alcohols, 1283 and E1 reactions, 1262 and E2 reactions, 1256 and E2C reactions, 1273 and Hofmann degradation, 1290 and nucleofuges, 1271 and pyrolytic elimination, 1281 and rearrangement of alkenes, 662 and stereochemistry, 1273 and sulfoxide elimination, 1296 and Wagner-Meerwein rearrangements, 1338 elimination of boranes, 1299 elimination reactions, failure of, 1270 zeolite Y, 215 zeolites, and addition of thiols to alkenes, 894 and carbocation formation, 215 and catalytic hydrogenation, 905 and conversion of aldehydes to nitriles, 1095 and dehydration, 1283 and Diels Alder reactions, 1023 and esterification, 1203 and Friedel-Crafts acylation, 622 and Friedel-Crafts acylation, 622 and halogenation of aromatic compounds, 607 and Meerwein-Ponndorf-Verley reduction, 1507 and oxidation of alcohols, 1446 and oxidation of tetrahydropyranyl ethers, 1452 and the Knoevenagel reaction, 1158 Ziegler alkylation, 785 Ziegler catalysts, coupling alkenes to alkenes, 933 zigzag acenes, 78 zinc chloride, and the Fischer indole synthesis, 1412 zinc cyanide, and the Gatterman reaction, 626 zinc, activated, and the Reformatsky reaction, 1129 allyl, reagents, with alkynes, 938 and cleavage of esters, 470 and dehalogenation of acyl halides to ketenes, 1306 and electrochemistry, 718 and elimination of dihalides to alkenes, 1304 and reduction of disulfides, 1555 and reduction of nitro compounds to hydroxylamines, 1526 and reduction of nitro compounds, 1528 and reduction of phenols the aromatic compounds, 1535 and ultrasound, 1129 as a complex, 1134 compounds, imines with ketene silyl acetals, 1137 in acid, and reduction of nitro compounds, 1524 zinc-amalgam and Wolff-Kishner reduction, 1540 SUBJECT INDEX zincates, dianion, 929 Zinin reduction, 1524 zip reaction, 1222 zirconium catalyst, silanes with dienes, 929 acyl, with allylic halides, 565 and Schwartz’s reagent, 926 Zn metal, and dehalogenation of propargylic halides, 1305 and conjugate addition reactions, 713 and elimination of halo ethers to alkenes, 1306 and selenide formation, 479 in acetic acid, reduction of conjugated systems, 916 in the Reformatsky reaction, 1130 with alcohols and acyl chlorides, 1201 2047 with allylic halides with nitriles, 1140 Zn-Cu, carbonylation, 565 Zr-Cr reagents, and alkynes, 933 zusammen, and alkene nomenclature, 163 zwitterion intermediates, and elimination of hydroxy acids, 1308 zwitterions, and oxime formation, 1095 ... Soc 20 00, 122 , 1550 1551 Kim, S.-W.; Son, S.U.; Lee, S.S.; Hyeon, T.; Chung, Y.K Chem Commun 20 01, 22 12; Son, S.U.; Lee, S.I.; Chung, Y.K.; Kim, S.-W.; Hyeon, T Org Lett 20 02, 4, 27 7 15 52 Krafft,... are not good OS I, 20 5, 521 ; II, 171, 177, 27 0, 408; III, 105, 123 , 127 , 20 9, 350, 526 , 531, 731, 785; IV, 130, 195, 748, 851, 969; V, 136, 370, 403, 467; VI, 21 0, 422 , 675, 8 62, 954; IX, 117;... Lett 20 03, 44, 1655 1 824 Seayad, J.; Seayad, A.M.; Chai, C.L.L Org Lett 20 10, 12, 14 12 1 825 Schultz, M.J.; Sigman, M.S J Am Chem Soc 20 06, 128 , 1460 1 826 Zhang, Y.; Sigman, M.S J Am Chem Soc 20 07,