16 nozaki hiyama kishi reaction

Myers Chem 115 The Nozaki-Hiyama-Kishi Reaction, Asymmetric Additions to Carbonyl Compounds Recent Reviews: • super-stoichiometric amounts of CrII reagents are generally employed Lumbroso, A.; Cooke, M L.; Breit, B Angew Chem Int Ed 2013, 52, 1890–1932 • aldehydes react markedly faster and with complete selectivity in the presence of ketones Hargaden, G C.; Guiry, P J Adv Synth Catal 2007, 349, 2407–2424 • because of the low basicity of organochromium reagents, the reaction is compatible with an array of functional groups Fürstner, A Chem Rev 1999, 99, 991–1045 • Coupling of an alkenyl halide or triflate wtih an aldehyde mediated by Cr(II) was first reported in 1977 and was found later to be initiated by a catalytic amount of NiCl2 • Examples: O MPMO H3C H3C Generalized Reaction Scheme: O R' X H R Typically: + CrII, OH NiII R H O H MOMO R' CH3 OCH3 O TfO H H3C Mechanism: OBn CH3 CrCl2 (90 mol%) NiCl2 (10 mol%) O H O CrII, NiII + I C4H9 Ph I Ni0 H3C NiI H3C C4H9 O OTBS Ph + H C4H9 transmetalation H O O H SEMO CH3 CH3 H O O H CH3 O H3C CH CH3 H3C Ph H3C Ph C4H9 CH3 CH3 CH3 O CH3 Br O O BnO OH work-up O 1% NiCl2/CrCl2 (14 equiv) DMF, 64% dr ~ : O O OCrIIICl2 C4H9 O OTBS O CrIICl2 O O H O O H THF, DMF, 23 ºC CH3 CH3 O H3C OBn CH3 CH3 CH3 CH3 O BnO O I NiII Cl2CrIII OMOM Product was not formed in the absence of 4-t-butylpyridine Stamos, D P.; Sheng, X C.; Chen, S S.; Kishi, Y Tetrahedron Lett 1997, 38, 6355–6358 C4H9 oxidative addition CrIICl2 I O OH C4H9 CrIIICl2I OCH3 O HO 4-t-butylpyridine CH3 CH3 • A specific example: H O • H • metal = Cr, Ni (sometimes Co) • X = Cl, Br, I, OSO2CF3, phosphonate O H3C DMSO, 23 ºC 92% single diastereomer CH3 Takao, K.; Hayakawa, N.; Yamada, R.; Yamaguchi, T.; Morita, U.; Kawasaki, S.; Tadano, K Angew Chem Int Ed 2008, 47, 3426–3429 • R' = allyl, aryl, alkenyl, alkynyl, propargyl Ph I O • OH MPMO H3C NiCl2 (6 mol%) CrCl2 (7.6 equiv) OTBS H OTBS O O H SEMO H H3C O HO H O O Huckins, J R.; de Vincente, J.; Rychnovsky, S D Org Lett 2007, 9, 4757–4760 O CH3 CH3 CH CH3 Fan Liu Myers • Synthesis of a palytoxin intermediate: O Chem 115 The Nozaki-Hiyama-Kishi Reaction, Asymmetric Additions to Carbonyl Compounds CH3 PMBO OPMB OTBS CH3 + I H3CO Catalytic in Chrominium: Addition of super stoichiometric amounts of the non-toxic metal manganese allows the reaction to proceed with catalytic amounts of Cr H CH3 CH3 H3C OPMB OPMB O O O H PMBO OPMB 1/2 Mn(0) OPMB BzO BzO OTMS C4H9 Ph OPMB OPMB CH3 OCH3 O OH CH3 0.11% NiCl2/CrCl2 (~30 equiv) DMSO, THF, 82% dr ~ 3.6 : • TMSCl + Mn(0): TMSCl serves to liberate CrIII from the product chromium alkoxide Mn(0) reduces CrIII to the catalytically active CrII species: 1/2 Mn(II) CrIIICl3 CrIICl2 Ph OBz C4H9 I NiI TMS-Cl OH OBz I NiII OCrIIICl2 C4H9 Cl2CrIII C4H9 O Ph H • Example: O CH3 PMBO OTBS CH3 OPMB OPMB OPMB O H3CO CH3 H3C CH3 O OH H PMBO OPMB OPMB OPMB OPMB CH3 OCH3 O OH CH3 O BzO BzO OH OBz OBz H3C OTf O + H O CrCl2 (15 mol%) (doped with cat NiCl2) Mn (1.7 equiv) OH O H3C TMSCl (2.4 equiv) DMF:DME, 50 ºC 80% O Fürstner, A.; Shi, N J Am Chem Soc 1996, 118, 12349–12357 • Zr(Cp)2Cl2 + Mn(0): use of Zr(Cp)2Cl2 in lieu of TMSCl suppresses formation of TMS enol ethers of aldehydes and increases the reaction rate • Example: Armstrong, R W.; Beau, J.-M.; Cheon, S H.; Christ, W J.; Fujioka, H.; Ham, W.-H.; Hawkins, L D.; Jin, H.; Kang, S H.; Kishi, Y.; Martinelli, M J.; McWhorter, W W.; Mizuno, M.; Nakata, M.; Stutz, A E.; Talamas, F X.; Taniguchi, M.; Tino, J A.; Ueda, K.; Uenishi, J.; White, J B.; Yonaga, M J Am Chem Soc 1989, 111, 7525–7530 H3C I CrCl2 (15 mol%) NiCl2(dppp) (2 mol%) Zr(Cp)2Cl2 (1 equiv) O + H Ph Mn (2 equiv) LiCl, MeCN 23 ºC, 71% OH H3C Ph Namba, K.; Kishi, Y Org Lett 2004, 6, 5031–5033 Fan Liu Myers The Nozaki-Hiyama-Kishi Reaction, Asymmetric Additions to Carbonyl Compounds Ligand Additives: Addition of supporting ligands often accelerates the reaction Use of chiral ligands affords enantiomerically enriched secondary alcohol products O N H O N N O t-Bu R = i-Pr R = t-Bu N Ph Ph A Cl H CH3 OH n-C5H11 n-Bu B n-Bu Ph Ph t-Bu H t-Bu O Br C H + H Ph (10) 23 84 71 (10) 23 83 96 (10) 23 90 92 (5) 23 – 93 (3) 23 90 98 (3) 23 71 94 17 94 OH Ph O 93 OH • Ligands on Ni, although not believed to be involved in the enantio-determining C–C bond-forming step, can have a dramatic influence on the enantioselectivity due to ligand scrambling: I 89 OH I n-Bu H3C OH B O Cr-4 (10 mol%) Ni catalyst I (2 mol%) Zr(Cp)2Cl2 (1 equiv) (10) n-C5H11 O I n-Bu H O Cl Cr O N ee (%) O S N yield (%) OH A O CH3 S N O temp (ºC) Ph O H R R Ph Br NH O S O ligand (mol%) OH A H OCH3 N product method O Br OCH3 OCH3 Ph Ph aldehyde nucleophile Chem 115 O H3C Br OH H3C 90%, 92% ee H Ph CH3 OH Ph Ph Mn (2 equiv) LiCl, MeCN, 23 ºC C CH3 Method A1: CrCl2 (10 mol%), Mn (2 equiv), DIPEA (30 mol%), TMSCl (2 equiv), THF; TBAF, THF N H3C N • NiCl2 I (NiCl2•DMP) Namba, K.; Cui, S.; Wang, J.; Kishi, Y Org Lett 2005, 7, 5417–5419 Liu, X.; Li, X.; Chen, Y.; Hu, Y.; Kishi, Y J Am Chem Soc 2012, 134, 6136–6139 Method B2: NiCl2•DMP (2 mol%), CrCl2 (10 mol%), Proton Sponge (11 mol%), LiCl (2 equiv), Mn (2 equiv), ZrCp2Cl2 (1 equiv), MeCN CH3 Method C3: Mn (3 equiv), TESCl (1.1 equiv), DME:MeCN; TBAF, THF 1Inoue, M.; Suzuki, T.; Nakada, M J Am Chem Soc 2003, 125, 1140–1141.; Inoue, M.; Nakada, M Org Lett 2004, 6, 2977–2980 2Namba, K.; Cui, S.; Wang, J.; Kishi, Y Org Lett 2005, 7, 5417–5419 3Xia, G.; Yamamoto, H J Am Chem Soc 2006, 128, 2554–2555 Fan Liu Myers The Nozaki-Hiyama-Kishi Reaction, Asymmetric Additions to Carbonyl Compounds • Ligand contains binding sites for both Ni and Cr and dramatically lowers the catalyst loading required for asymmetric addition Cr-8 (1 mol%) • catalysts can override inherent selectivities of the substrate: + O I OBz Cr-Ligand (20 mol%) NiCl2 (2 mol%) LiCl (2 equiv) Mn (2 equiv) OBz Cl OTBDPS H R OH 3,3'-dimethyl2,2'-dipyridine (S)-5 (R)-5 (S)-6 (R)-6 (S)-7 (R)-7 I H3C Cl NiCl2 (1 mol%) Zr(Cp)2Cl2 (1.2 equiv) Mn (2 equiv) O + Ph H OTBDPS Zr(Cp)2Cl2 (1 equiv) MeCN, 23 ºC Ligands O dr (S : R) H3C : 8.0 8.1 : N CH3 CH3 Liu, X.; Henderson, J.; Sasaki, T.; Kishi, Y J Am Chem Soc 2009, 131, 16678–16680 Peng, J.; Kishi, Y Org Lett 2012, 14, 86–89 Cl 16 : • Ligands for the enantioselective allylation and propargylation of ketones have been developed: : 21 24 : CrCl3 (10 mol%) Ligand (10 mol%) O + R' CH3 nucleophile O N OCH3 N N i-Pr NH O S O CH3 m-CF3Ph N i-Pr NH O S O CH3 t-Bu temp (ºC) yield (%) ee (%) 63 91 R CH3 i-Pr O 69 88 (anti) 70 (syn) O N H N Ph Boc Bn CH3 NH O S O Cl HO CH3 N O Cl O N O 10a 25 70 70 H3CO n-Bu HO CH3 H N S N Cl ligand R' OCH3 N O Et3N, TMSCl Mn (2 equiv), THF OH HO CH3 Br O HO CH3 Br H3C CH3 product nucleophile 3,3'-dimethyl-2,2'-dipyridine O Ph N NH O S O Cl : 15 OH H3C LiCl, MeCN, 23 ºC >90%, 82% ee O N 1.2 : R X H3C H3C Chem 115 10a 25 86 N H Boc H N 96 t-Bu 10 Cl S Guo, H.; Dong, C.-G.; Kim, D.-S.; Urabe, D.; Wang, J.; Kim, J T.; Liu, X.; Sasaki, T.; Kishi, Y J Am Chem Soc 2009, 131, 15387–15393 Cl HO CH3 10a 25 75 92 a1 equiv of LiCl was added Ph Miller, J.; Sigman, M S J Am Chem Soc 2007, 129, 2752–2753 Harper, K C.; Sigman, M S Science 2011, 333, 1875–1878 Fan Liu Myers TBSO H3C • Examples in synthesis: • A one-pot NHK-Peterson elimination strategy was used for the large-scale synthesis of the anticancer marine natural product discodermolide: CH3 CH3 CH3 CH3 CHO OTBS OPMB CH3 H3C OTBS OTES TBSO OPiv CH3 H THF, 0–15 ºC R PMBO OTBS CH3 CH3 CH3 TMS TBSO H3C OH + CH3 OTBS OPMB CH3 H3C OTBS M KOH PMBO CH3OH, 23 ºC 81% (2 steps) OBn CH3 CH3 100%, dr = : O H H Cr-11 (20 mol%) NiCl2(P(CH3))2 (4 mol%) O ZrCp2Cl2, Mn LiCl, MeCN, 23 ºC OBn OBn dr = 30 : yield not reported TBSO H3C CH3 CH3 93%, dr = 18 : steps O OH H OBn OBn O OCH3 N i-Pr O Liu, X.; Li, X.; Chen, Y.; Hu, Y.; Kishi Y J Am Chem Soc 2012, 134, 6136–6139 O O CH3 CH3 H3CO DMBOMO CH3 OH OAc I H3CO CH3 H OTr CH3 O CH3 CH3 OCH3 OCH3 O O O CH3 H3CO DMBOMO OTr CH3 CH3 CH3 OCH3 N OAc H3CO CH3 S OMTM 76%, dr = : N N TBSO H3C OMTM CH3 CH3 2,4,6-Cl3C6H4COCl Et3N, DMAP, THF, quan CH3 TBSO H3C O CH3 OTBS ent-12 (10 equiv) CH3CN OAc OTr + H3CO OTBS NH O S O HO H3CO DMBOMO I CH3 CrCl2 (10 equiv) NiCl2(dppp) (4 mol%) proton sponge OBn O OH CH3 S OTBS OMTM OBn BnO O + I OH OAc OTr steps H3C H3C OBn O OCH3 (1.27 kg) BnO O O CH3 CH3 OTBS OH Mickel, S J.; Sedelmeier, G H.; Niederer, D.; Schuerch, F.; Seger, M.; Schreiner, K.; Daeffler, R.; Osmani, A.; Bixel, D.; Loiseleur, O.; Cercus, J.; Stettler, H.; Schaer, K.; Gamboni, R.; Bach, A.; Chen, G.-P.; Chen, W.; Geng, P.; Lee, G T.; Loeser, E.; McKenna, J.; Kinder, F R., Jr.; Konigsberger, K.; Prasad, K.; Ramsey, T M.; Reel, N.; Repic, O.; Rogers, L.; Shieh, W.-C.; Wang, R.-M.; Waykole, L.; Xue, S.; Florence, G.; Paterson, I Org Process Res Dev 2004, 8, 113–121 H3C H3C OTr TBSO CH3 HO R OAc H TBSO OPiv CH3 CH3 TMS PMBO O OTES CH3 CH3 CH3 CH3 + CrCl2 (10 equiv) NiCl2(dppp) (1 mol%) proton sponge 12 (10 equiv) CH3CN CH3 I (1.52 kg) I TBSO + O TMS CrCl2 (4.3 equiv) OCH3 CH3 Br PMBO Chem 115 The Nozaki-Hiyama-Kishi Reaction, Asymmetric Additions to Carbonyl Compounds t-Bu NH O S O CH3 12 11 Kobayashi, K.; Fujii, Y.; Hayakawa, I.; Kigoshi, H Org Lett 2011, 13, 900–903 Kobayashi, K.; Fujii, Y.; Hirayama, Y.; Kobayashi, S.; Hayakawa, I.; Kigoshi, H Org Lett 2012, 14, Fan Liu 1290–1293 Myers Chem 115 The Nozaki-Hiyama-Kishi Reaction, Asymmetric Additions to Carbonyl Compounds • Application to the synthesis of the anticancer drug Halaven!: TBSO O OCH3 N CH3 CrCl2, NiCl2 Et3N, 13 CH3 O Br OH OTs KHMDS, THF TBSO TBSO O HO MsO H3CO + O OPiv (1.48 kg) OPiv SO2Ph O H TBSO TBSO CH3 O H • CH3 n-BuLi THF-heptane