30 cyclobutane synthesis

O MV2+ = methyl viologen (N,N'-dimethyl-4,4'-bypyridinium) H3C N H3CO Ph visible light MgSO4, MeNO2 88%, dr >10:1 O mol% Ru(bpy)3(PF6)2 15 mol% MV(PF6)2 H H O • Limitation of the method: at least one of the styrenes must bear an electron-donating substituent at the para or ortho position Aliphatic olefins are not suitable reaction partners N CH3 • Mechanism: *Ru(bpy)32+ strong reductant visible light • Photoredox catalysis can also be used for [2+2] cycloadditions of enones: N CH3 (MV2+) H3C N Me N +1 e- N Me Ph (MV-radical) Ru(bpy)32+ photocatalyst O O Ph product Ru(bpy)33+ strong oxidant visible light Ru(bpy)3Cl2 (5 mol%) O O H H Ph Ph LiBF4, i-Pr2NEt MeCN, 89%, dr >10:1 MV2+ -1 e- +1 e– OCH3 p-CH3OC6H4 MV-radical Ph OR p-CH3OC6H4 O O Ph H H O O Ph CH3 CH3 visible light Ru(bpy)3Cl2 (5 mol%) LiBF4, i-Pr2NEt MeCN, 84%, dr >10:1 O Ph O CH3 H3C • Upon photoexcitation, the photocatalyst (Ru(bpy)3(PF6)2) acts as a strong reductant, reducing MV by a single electron • The resulting Ru(III) species acts as a strong oxidant, which oxidizes the electron-rich styrene to produce a radical cation and regenerates photocatalyst • The resulting radical cation undergoes cyclization Ischay, M A.; Lu, Z.; Yoon, T P J Am Chem Soc 2010, 132, 8572–8574 Ischay, M A.; Anzovino, M.E.; Du, J.; Yoon, T.P J Am Chem Soc 2008, 130, 12886–12887 Du, J.; Yoon, T.P J Am Chem Soc 2009, 131, 14604–14605 Danica Rankic Myers Chem 115 Cyclobutane Synthesis • Mechanism: • An intramolecular variant was also developed • The product can be converted to acids, esters, thioesters and amides: visible light *Ru(bpy)3 2+ i-Pr2NEt Li O LiBF4 Ph Ru(bpy)32+ O N i-Pr2NEt +1 e– Ru(bpy)3+ Li –1 e– CH3 O N O visible light Ru(bpy)3Cl2 (2.5 mol%) OBn LiBF4, i-Pr2NEt MeCN, 87%, dr >10:1 O Ph Ph Me CH3 Me O O O H H BnHN CH3 O O N H H H3C N OBn MeOTf, CH2Cl2 67% BnNH2, DBU CH2Cl2, 98% OBn 98%, dr >10:1 Li O O Ph –1 e– CH3 Ph H3C Li O O CH3 H3C Tyson, E L.; Farney, E P.; Yoon, T P Org Lett 2012, 14, 1110–1113 O O Ph CH3 • Styrenes and alkenes undergo [2+2] cycloaddition in the presence of an Ir catalyst (III) and light The catalyst functions as a photosensitizer H3C CF3 F • Lewis acid coordination decreases the reduction potential of the enone, facilitating single electron transfer • Limitation of the method: one coupling partner must be an aromatic ketone Aliphatic ketones and esters not under go cycloaddition because of their higher reduction potentials Ph CH3 visible light III (1 mol%) CH3 CH3 H Ph CH3 H DMSO, 83% O N F OH EtO2C H3C O H3C N N visible light Ru(bpy)3Cl2 (2.5 mol%) O CH3 i-Pr LiBF4, i-Pr2NEt MeCN, 73%, dr >10:1 H3C N O CH3 F N N O F CH3 O CH3 EtO2C DMSO, 86% H3C t-Bu CF3 III H3C CH3 H H • O CH3 O CH3 N i-Pr HO visible light III (1 mol%) PF6– IrIII Ischay, M A.; Anzovino, M.E.; Du, J.; Yoon, T.P J Am Chem Soc 2008, 130, 12886–12887 Du, J.; Yoon, T.P J Am Chem Soc 2009, 131, 14604–14605 • !,"-Unsaturated 2-imidazolyl ketones also undergo photochemically induced cycloadditions: t-Bu N HO HO2C H3C H3C CH3 H H • O LiOH 60 ºC 97% CH3 (±)-cannabiorcicyclolic acid Lu, Z.; Yoon, T P Angew Chem Int Ed 2012, 51, 10329–10332 Danica Rankic Myers Chem 115 Cyclobutane Synthesis • Other Methods for Cyclobutane Synthesis • Gold(I)-Catalyzed Ring Expansion of Cyclopropanes • Brook Rearrangement of 1,4-Dicarbonyls • Alkynyl cyclopropanols can undergo ring expansion upon treatment with catalytic Au(I): • Treatment of keto acylsilanes with organolithium reagents produces highly functionalized cyclobutanes favoring cis-stereochemistry between newly formed alcohols t-Bu PhLi, THF i-Pr TBS O O –80 " –30 ºC TBSO Ph OH i-Pr HO Ph 67% HO OTBS [(p-CF3C6H4)3P]AuCl (0.5 mol%) AgSbF6 (0.5 mol%) O CH2Cl2, 23 ºC, 98% i-Pr single isomer 10% Mechanism: • The mechanism is proposed to involve a stereospecific 1,2-alkyl shift: i-Pr TBS O Ph O TBSO Ph i-Pr O TBS O OH i-Pr Ph Li [(p-CF3C6H4)3P]AuCl (1 mol%) AgSbF6 (1 mol%) Ph O TBSO CH2Cl2, 23 ºC, 94% Brook rearrangement H3C H3C CH3 AuL • Ring Expansion of Cyclopropanes via Pinacol-Type Rearrangements TBSO • Hydroxycyclopropyl carbinols can be ring-expanded by treatment with protic or Lewis acids H3C • Either cis- or trans-substituted cyclobutanones could be produced from a single diastereomer of a an !-hydroxycyclopropyl carbinol: BF3•Et2O (20 mol%) O n-Bu 80% 17:1 cis:trans concerted migration proposed THF, 23 ºC HO Ph CH3 H+ Takeda, K.; Haraguchi, H.; Okamoto, Y Org Lett 2003, 5, 3705–3707 Ph t-Bu p-TsOH•H2O (10 mol%) O CHCl3, 23 ºC Ph Ph AuL O CH3 H3C Ph CH3 Markham, J P.; Staben, S T.; Toste, D F J Am Chem Soc 2005, 127, 9708–9709 n-Bu Ph OH single diastereomer n-Bu 94% 1:17 cis:trans thermodynamic product Hussain, M M.; Li, H.; Hussain, N.; Urena, M.; Carroll, P J.; Walsh, P J J Am Chem Soc 2009, 131, 6516–6524 Danica Rankic Myers Chem 115 Cyclobutane Synthesis • Cu-catalyzed 1,4-Ring closure • The products can be derivatized: • Homoallylic sulfonates can undergo borylation/cyclization using a CuI catalyst: Bn(H3C)2Si OMs Ph CuCl (5 mol%) dppp (5 mol%) Ph B2pin2, KOt-Bu THF, 23 ºC H3C CH CH3 O B O CH3 O CH3 CH3 CH3 CH3 O B B O O B2pin2 CuCl (5 mol%) dppp (5 mol%) (H3C)2PhSi OMs (H3C)2PhSi H3C H3C H3C H3C H3C CH CH3 O B O CH3 TBAF, THF 23 ºC H2O2, KHCO3 CH3OH, 23 ºC OBz 49% (2 steps) (dppp)Cu (dppp)CuI-Bpin R2 OBz Bpin H R1 OMs +KOt-Bu Bpin HO OMs (dppp)CuIOt-Bu R1 OBz R1 pinB Ot-Bu pinB!Bpin OBz HO TBAF, THF 23 ºC H2O2, KHCO3 CH3OH, 23 ºC 57% (2 steps) R2 R2 Bn(H3C)2Si PhCOCl, C5H5N CH2Cl2, ºC 61% (2 steps) LiCH2Cl, THF –78 " 23 ºC H2O2, NaOH THF, ºC PhCOCl, C5H5N CH2Cl2, ºC 73% (3 steps) R3Si H2O2, NaOH THF, ºC B2pin2, KOt-Bu THF, 23 ºC • Mechanism: CuCl BPin R2 R1 R2 Bpin H tBuO CuIII dppp R1 t-BuO K+ CuI dppp Bpin Ph BPin BCl3, CH2Cl2 23 ºC Ph NHBn BnN3, CH2Cl2 ºC, 57% • Note that in each case the stereochemistry of the starting material is preserved in the product H OMs KOMs • Limitation of the method: only aryl- or silyl-substituted olefins react; alkyl olefins not undergo borocupration Ito, H.; Toyoda, T.; Sawamura, M J Am Chem Soc 2010, 132, 5990–5992 Markham, J P.; Staben, S T.; Toste, D F J Am Chem Soc 2005, 127, 9708–9709 Danica Rankic 10 ... Angew Chem Int Ed 2012, 51, 10329–10332 Danica Rankic Myers Chem 115 Cyclobutane Synthesis • Other Methods for Cyclobutane Synthesis • Gold(I)-Catalyzed Ring Expansion of Cyclopropanes • Brook...Myers Chem 115 Cyclobutane Synthesis • Mechanism: • An intramolecular variant was also developed • The product can be... organolithium reagents produces highly functionalized cyclobutanes favoring cis-stereochemistry between newly formed alcohols t-Bu PhLi, THF i-Pr TBS O O –80 " ? ?30 ºC TBSO Ph OH i-Pr HO Ph 67% HO OTBS [(p-CF3C6H4)3P]AuCl