Chemistry 206 Advanced Organic Chemistry Handout -19A Enantioselective Carbonyl Addition Handout Enantioselective addition of rzN to aldehydes Enantioselective Reduction of Ketones Imines Matthew. shair Friday ay November 1. 2002
Chemistry 206 Advanced Organic Chemistry Handout–19A Enantioselective Carbonyl Addition Handout Matthew D. Shair Friday, November 1, 2002 ■ Enantioselective addition of R2Zn to aldehydes ■ Enantioselective Reduction of Ketones & Imines
D. A. Evans Enantioselective C=O Addition: Noyori Catalyst Chem 115 Catalytic Asymmetric Carbonyl Addition The Catalytic Cycle place with chiral controller the catalyst Noyori& co-workers, J. Am. Chem. Soc. 1986, 108, 6072 JAm.chem.Soc.1989,111,4028 Review: Noyori Angew. Chem. Int. Ed. 1991, 30, 49 E- Et 2Zn the catalyst (DAlB-ZI 59-97% C6H5CHO 98%ee.: Catalyst must be sterically hindered so that association is precluded p-CICBH4CHO EtZ 93%ee 93%ee. n-C6H13CHO 61%ee. 4 RO-ZnR ne method is catalytic in aminoalcohol a Two zinc species per aldehyde are involved in the alkylation step a Product is taken out of the picture by aggregation 19A01-Et2Zn-11/1900149PM
00 00 0000 0000 0000 Review: Noyori Angew. Chem. Int. Ed. 1991, 30, 49 the catalyst ■ Two zinc species per aldehyde are involved in the alkylation step. ■ Product is taken out of the picture by aggregation 4 ■ The method is catalytic in aminoalcohol. D. A. Evans Enantioselective C=O Addition: Noyori Catalyst Chem 115 Noyori & co-workers, J. Am. Chem. Soc. 1986, 108, 6072. replace with chiral controller Catalytic Asymmetric Carbonyl Addition 98% e.e. ■ Catalyst must be sterically hindered so that association is precluded 91% e.e. 93% e.e. 93% e.e. 96% e.e. 90% e.e. 61% e.e. Et2Zn Me2Zn Et2Zn Et2Zn Et2Zn Et2Zn Et2Zn C6H5CHO " p-ClC6H4CHO p-MeOC6H4CHO Cinnamyl PhCH2CH2CHO n-C6H13CHO 0°C, toluene 59 - 97% Ar–CHO + R2’Zn J. Am. Chem. Soc. 1989, 111, 4028. the catalyst the catalyst Et2Zn 90-98% ee RDS The Catalytic Cycle (DAIB-Zn) Zn R Zn I I C O R R H Me Me N H Me Me Me O Zn H Et Me Me N H Me Ar R’ OH Me Me O Zn H Et O C H Zn Et Et Zn Et C Et O H O Zn Et H H N Me Me Me Me Me O C H Et H O Zn Et H H O N Me Me Me Me Me Me Me N H Me Me Me O Zn H Et Zn–Et O C H R' O Zn O Zn Zn O O Zn R R R R'O ZnR R' Zn R R' R' O R R' O R' Zn R O Zn Zn O R R' R' R Zn Et H H O N Me Me Me Me Me 19A-01-Et2Zn-1 1/19/00 1:49 PM
D A. Evans Enantioselective C=O Addition: Noyori Catalyst-2 Chem 115 Other Catalysts for the R2Zn Addition Process Explanation for Nonlinearity of DAlB Catalyst Me3C Et 97%ee.(S) 100%ee.(R) 95%ee.(S) (S, S)dimer (R, R)dimer 90%ee.(R) 90%ee(R) 90%ee.(R) (Results are cited for the reaction of benzaldehyde and Et2Zn) Problem: Rationalize the stereochemical course of each of the catalysts (S)catalyst (R)catalyst Non-linear effects observed with the Noyori Catalyst(DAlB-Zn) There is no corel ion hetween I (S, R)dimer Et2Zn PhCHO (%ee) bservations (S,S)dimer dissociates upon addition of RCHo effects catalys 25%ee Catalyst affords product in 95%ee (s, R )dimer is overwhelmingly more stable than(s,S)homodimer a(S, R )dimer is ineffective as a catalyst %ee of catalyst 19A02Et2Zn11/1900149PM
Other Catalysts for the R2Zn Addition Process D. A. Evans Enantioselective C=O Addition: Noyori Catalyst-2 Chem 115 ■ Non-linear effects observed with the Noyori Catalyst (DAIB-Zn) Product (%ee) 100 %ee of catalyst 100 25% ee Catalyst affords product in 95% ee. There is no correlation between catalyst and product ee. Et2Zn + PhCHO (S,S) dimer (R,R) dimer + (S) catalyst (R) catalyst (S) catalyst 90% e.e. (R) 90% e.e. (R) 90% e.e. (R) (Results are cited for the reaction of benzaldehyde and Et2Zn) 97% e.e. (S) 100% e.e. (R) 95% e.e. (S) Problem: Rationalize the stereochemical course of each of the catalysts Explanation for Nonlinearity of DAIB Catalyst (S,R) dimer Observations ■ (S,S) dimer dissociates upon addition of RCHO & effects catalysis ■ (S,R) dimer is overwhelmingly more stable than (S,S) homodimer ■ (S,R) dimer is ineffective as a catalyst Ph Me OH O Zn Me2 N Me Zn Me Me2 N O Zn Me Me2 N O O Zn N Me2 Me Zn O O Zn Me NMe2 Me2 N Me Zn O O Zn Me NMe2 N Zn O Me Ph Ph Et Zn Et Ph H N O Me3C Me2 N Me Li O N Me Me N Me H H Ph H Ph N O N Li N Me Me Me Me N Zn N Bu Me O Et Li Li Bu Ph 19A-02-Et2Zn-1 1/19/00 1:49 PM
D. A. Evans Enantioselective C=O Addition: Dialkylzinc Addn Scope Chem 115 Improved Selectivity with Aliphatic Aldehydes Scope of the DAlB Catalyst Soai, J. Org. Chem. 1991, 56, 4264 (S)catalyst (S)catalyst (6%) Et2Zn 98%ee RCHo+ 0°c, hexane 70-100% (S)catalyst 91%ee 88%ee 78%ee 95%ee93%ee (S)catalyst Lepicidin Application The reaction functions in complex systems Bu3Sn (n-Pen)2Zn 85%ee the catalyst (S)catalyst Evans, Black, JACS 1993, 115, 44974513 OTIPS Et2Zn 60%ee OTES Et24 0°c, hexane Review. Noyon Angew. Chem. Int. Ed. 1991, 30, 49 10.:1(98%) 19A-03-Et2Zn-Scope 1/19/00 1: 49 PM
88% ee 78% ee 95% ee 93% ee Improved Selectivity with Aliphatic Aldehydes Soai, J. Org. Chem. 1991, 56, 4264 (6%) RCHO + Et2Zn 0 °C, hexane 70 - 100% 60% ee Et2Zn (S) catalyst Review: Noyori Angew. Chem. Int. Ed. 1991, 30, 49 (S) catalyst Et2Zn 90% ee (S) catalyst (n-Pen)2Zn 85% ee 96% ee Et2Zn (S) catalyst (S) catalyst Me2Zn 91% ee 98% ee Et2Zn (S) catalyst Scope of the DAIB Catalyst (S) catalyst D. A. Evans Enantioselective C=O Addition: Dialkylzinc Addn Scope Chem 115 Lepicidin Application: The reaction functions in complex systems 3 9 Et2Zn, 3 3 15 15 11 diastereoselection 10:1 (98%) 21 the catalyst 21 21 0 °C, hexane Evans, Black, JACS 1993, 115, 44974513 H O OH Et Me OH O Zn Me2 N Me Ph N O Bu Et Zn Me Bu R Et OH O O n-Bu H H O O H Me H Me O OR OR O O Me Et H H H H H MeO OTIPS OTES O O H H O OH H Bu3Sn Me H O Et OH MeO SnBu3 OTIPS OTES O Me C5H11 OH O H H OH O Bu3Sn H n-Bu SnBu3 H H Zn H O OH H N Bu Me O Et Bu n-Bu Ph 19A-03-Et2Zn-Scope 1/19/00 1:49 PM
A. Evans Enantioselective C=O Addition: Dialkylzinc Addn Scope Chem 115 Other Catalysts for Aliphatic Aldehydes Utilization of Grignard and Alkenyllithium Reagents NHSO2 CF3 Ph RCHO Et2Zn ligand Ti(OR)4 Temp (R,R, R, R)- (RR-2 HcHO 0.04 equiv 1.2 equiv. -20C 98%ee 1)ZnCl2, Et20, 23C 2)dioxane; filter PhCH=CHCHo 0.02 equiv 0.3 equiv -50C 99% ee H2MgX3)0.15eq1,78c PhCH2 CH CHo 0.01 equiv 0.6 equiv 0C 92%ee 4)1.2 eq. Ti(OiPr)4 0.04 equiv 0.6 equiv -20C 99%ee 5)R2 CHO to30°c n-CsH11CHO Ohno. Tet. Lett. 1989. 30. 7095 RCHO Yield % MeMg HcHO Knochel has described preparation of functionalized R2Zn reagents 55%94% n-BuMgBr HcHO 82%96% R-l Et2zn CH2=CH(CH2 2MgBr PhC 83%90% distill Et2Zn Et-l 40%≥90% i-PrCHo n-BuMaBl 35%90% RzN C6H11CHO 69%95% MeMg CH2=CH(CH2)3CHO X=CL OAC 60%≥90% n-PrMgBr CHo Ohno Reagent 2 is a more effective or the addition of Et2zn to aldehydes t-BuO t-Buo Seebach, Angew. Chem. Int. Ed. 1991, 30, 1008, and 1321 92%ee(90% yield 2 R-MgX ZnCl2 R2-Zn MgX2 MgCl2 Knochel, J. Org. Chem. 1992, 57, 1956 Mg×2+ dioxane roxane comple 19A-04-Et2Zn-Scope-2 1/19/00 1: 49 PM
MgX MgX2–dioxane complex 2 + dioxane 2 R–MgX + ZnCl2 R2–Zn + MgX2 + MgCl2 D. A. Evans Enantioselective C=O Addition: Dialkylzinc Addn Scope Chem 115 Ohno, Tet. Lett. 1989, 30, 7095 RCHO + Et2Zn Ti(O-i-Pr)4 toluene-hexane 78 - 95% ■ Knochel has described preparation of functionalized R2Zn reagents Knochel, J. Org. Chem. 1992, 57, 1956 Other Catalysts for Aliphatic Aldehydes -20 °C -50 °C 0 °C -20 °C 0.04 equiv 0.02 equiv 0.01 equiv 0.04 equiv 98% ee 99% ee 92% ee 99% ee 1.2 equiv. 0.3 equiv 0.6 equiv 0.6 equiv PhCHO PhCH=CHCHO PhCH2CH2CHO n-C5H11CHO aldehyde ligand Ti(OR)4 Temp ee R–I + Et2Zn 3-5 equiv Et–I + R–Zn–Et distill R2Zn – Et2Zn + Et–I 2 X = Cl, OAc 2 Ohno catalyst PhCHO 92% ee (90% yield) Reagent 2 is a more effective catalyst for the addition of Et2Zn to aldehydes MeMgI n-BuMgBr CH2=CH(CH2)2MgBr MeMgBr n-BuMgBr MeMgI n-PrMgBr PhCHO PhCHO PhCHO i-PrCHO C6H11CHO CH2=CH(CH2)3CHO Ph(CH2)2CHO 55% 82% 83% 40% 35% 69% 60% 94% 96% 90% ≥90% 90% 95% ≥90% R1-CH2MgX (2 equiv.) 1) ZnCl2, Et2O, 23°C 2) dioxane; filter 3) 0.15 eq. 1, -78°C 4) 1.2 eq. Ti(OiPr)4 5) R2CHO to -30°C (R,R,R,R)-1 (R,R)-2 Utilization of Grignard and Alkenyllithium Reagents Seebach, Angew. Chem. Int. Ed. 1991, 30, 1008, and 1321 Grignard RCHO % Yield % ee X Zn O t-BuO Zn t-BuO O Ph OH O Ti O O O O Me O Ph Me Ph Ph Ph O O Me Ph Me Ph Ph Ph OH R Et NHSO2CF3 NHSO2CF3 O Ti O O O O–CHMe2 Me Ph Me Ph Ph Ph O–CHMe2 R2 OH R1 19A-04-Et2Zn-Scope-2 1/19/00 1:49 PM
D. A. Evans. D M. Barnes Allyl and Crotyl Metal Species-4: Catalytic Systems a Three Catalytic Asymmetric Allylations of Aldehydes are Known Ti(OiPr)4, 4A sieves COOH +BH3THF— 20 mol % BLn HcHO Ti(OiPr 4A EZ 63% yield CF3COOH or TfOH 90% H. Yamamoto, Synlett 1991, 561-562. 102(10m%)RCHo Yield (% 88 20 mol 42 n-C7H15CHO G. Keck J. Am. chem. Soc. 1993. 115. 8467-8468 ETagliavini,A. Umani-Ronchi J. Am. Chem. Soc. 1993, 115, 7001-7002. i Many Other Metals Have Been Employed in the Allylation Reaction Pb: S. Toni. Chem. Lett. 1986. 1461-1462 Mo: J Faller. Tetrahedron Lett. 1991. 32. 1271-1274 Cr: Y Kishi. Tetrahedron Lett. 1982. 23. 2343-2346 b: Y. Butsugan, Tetrahedron ron lett1987,28,3707-3708 Mn: T. Hiyama, OrganometalliCS, 1982, 1, 1249-1251 Zn: T Shono. Chem. Lett. 1990. 449-452 Ba: H. Yamamoto. J. Am. Chem. Soc. 1991. 113. 8955-8956 19A-04a-Allyl/Crotyl 4 1/19/00 1: 49 PM
Pb: S. Torii, Chem. Lett. 1986, 1461-1462. Mo: J. Faller, Tetrahedron Lett. 1991, 32, 1271-1274. Cr: Y. Kishi, Tetrahedron Lett. 1982, 23, 2343-2346. P. Knochel, J. Org. Chem. 1992, 57, 6384-6386. Sb: Y. Butsugan, Tetrahedron Lett. 1987, 28, 3707-3708. Mn: T. Hiyama, Organometallics, 1982, 1, 1249-1251. Zn: T. Shono, Chem. Lett. 1990, 449-452. Ba: H. Yamamoto, J. Am. Chem. Soc. 1991, 113, 8955-8956. ■ Many Other Metals Have Been Employed in the Allylation Reaction ... D. A. Evans, D. M. Barnes Allyl and Crotyl Metal Species-4: Catalytic Systems Chem 115 ■ Three Catalytic Asymmetric Allylations of Aldehydes are Known + BH3-THF BLn* E/Z = 61/39 + PhCHO 20 mol % BLn* H. Yamamoto, Synlett 1991, 561-562. n-C7H15CHO + 81% yield 97.4% ee 63% yield 90% ee E. Tagliavini, A. Umani-Ronchi J. Am. Chem. Soc. 1993, 115, 7001-7002. G. Keck J. Am. Chem. Soc. 1993, 115, 8467-8468. 20 mol % Ti(OiPr)4, 4Â sieves Ti(OiPr)4, 4Â sieves CF3COOH or TfOH 1 2 1 or 2 (10 mol %), RCHO R Ph Chex Catalyst 1 2 1 2 1 2 Yield (%) 88 98 66 95 42 78 ee (%) 95 92 94 92 89 77 COOH iPrO OiPr O OH COOH Me SiMe3 Me Ph Me OH Me O O Ti Cl Cl SnBu3 n-C7H15 OH H O SnBu3 R OH OH OH O O Ti OiPr OiPr OH OH O O Ti O O 19A-04a - Allyl/Crotyl 4 1/19/00 1:49 PM
D. A. Evans Enantioselective c=o Addition Ketone reduction Chem 115 Stoichiometric Chloroborane Reducing Agents Enantioselective Reducing Agent N-Methylephedrine LIAIH4, (3, 5-Xylenol)2 2 [LiAl(ig)(OAr)2H] 5090% (R)-Alpine borane Me (S)-BINAL-H Darvon alcohol, LIAIH4 LIAl(ig)2H Reviews: Midland, Asymmetric Synthesis, Vol 2, p 45. 3, 3-dimethyl-2-butanone 25.C, 12 days 5% Granbois, Asymmetric Synthesis, Vol 2, p 71 Brown. Accts. Chem. Res. 1992. 25. 16-24 25°C,2days 91% Singh, Synthesis 1992, 605-617 Reductions of Representative Carbonyl Compounds Brown's model Alpine-Borane 72-92%ee 59.89%ee.78%ee.R=Me 90%e e R=CO Me d Large ligand (RU) BINAL-H 84.96%ee.>95%ee.95-100%ee. (57%ee, R=i-Pr) (71%ee,R=-Pr) Rs Favored TS Small ligand(Rs) Darvon-LiAIH4 34-90%e e. 25% 15-75%ee Less hindered aliphatic ketones are not reduced with useful Brown, J. Org. Chem. 1986, 51, 3394 N-Methylephedrine-75-90%ee. 78-98%ee levels of enantioselectivity 19A-05 Asym Red-11/19001:48PM
00 00 000 000 Brown's Model D. A. Evans Enantioselective C=O Addition: Ketone Reduction Chem 115 (R)-Alpine Borane Li + (S)-BINAL-H Enantioselective Reducing Agents Darvon alcohol, LiAlH4 [LiAl(lig)2H] N-Methylephedrine, LiAlH4, (3,5-xylenol)2 [LiAl(lig)(OAr)2H] - Reviews: Midland, Asymmetric Synthesis, Vol 2, p 45- Granbois, Asymmetric Synthesis, Vol 2, p 71- Brown, Accts. Chem. Res. 1992, 25, 16-24 Singh, Synthesis 1992, 605-617 78% e.e. R=Me 90% e.e. R=CO2Me 95 - 100% e.e. (71% ee, R=i-Pr) 15 - 75% e.e. ---- 59 - 89% e.e. >95% e.e. 25% e.e. 78 - 98% e.e. (cyclic ketones) 72 - 92% e.e. 84 - 96% e.e. (57% ee, R=i-Pr) 34 - 90% e.e. 75 - 90% e.e. Alpine-Borane BINAL-H Darvon-LiAlH4 N-Methylephedrine- LiAlH4 Reagent Reductions of Representative Carbonyl Compounds THF 50 - 90% Less hindered aliphatic ketones are not reduced with useful levels of enantioselectivity 2 Brown, J. Org. Chem. 1985, 50, 5446 98% 98% 79% 95% 91% -25 °C -25 °C -25 °C 25°C, 12 days 25°C, 2 days acetophenone butyrophenone 2,2-dimethylpropiophenone 3,3-dimethyl-2-butanone 2,2-dimethylcyclohexanone Ketone Reaction Conditions % ee Brown, J. Org. Chem. 1986, 51, 3394 Brown, J. Org. Chem. 1988, 53, 2916 Stoichiometric Chloroborane Reducing Agents Small ligand (Rs) Large ligand (RL) Favored TS Me B O O Al H OEt Bn Ph Ph Me Me2N OH NMe2 OH Me O R R O R O Me B Cl RL RS O OH RL RS X B Me Me Me H H O RL RS Y 19A-05-Asym Redn-1 1/19/00 1:48 PM
D. A. Evans Enantioselective c=o Addition Ketone Reduction -2 Chem 115 Improved Enantioselectivity with Alphatic Ketones Miscellaneous Chiral Borohydride Reagents chem.1989,54, Rxn time Brown, J. Org. Chem. 1988, 53, 1231 Ketone THF,23°℃)%conV.%ee Brown. J. Am. Chem. Soc. 1988. 110 1539 7 day 3-methyl-2-butanone 2 days 100%88% cyclohexyl methyl ketone 4 days 86% R=t-Bu 87%ee. 92%ee. 4 days 72% cyclohexenone 4 days 50%79% THF,-78°C Brown Tetrahedron Let. 1991. 32 6691 PhCoHN-+H HT NHCOP LiBH4/EtOH Rxn time (1:3:13) Ketone (THF,-25°℃)%com.%ee >99% 78°C.THF 2, 2-dimethylcyclopentanone trans-4-phenyl-3-buten-2-one 14d 2-cyclohexenone 60%74% -BuOH replacing EtOH OH 83%e e (R) 4-phenyl-3-butyn-2-one 5h 82%33% Soai. Chem. Commun. 1987. 801: Chem. Commun. 1986. 1018 19A-06- Asym Red-21/19001:48PM
LiBH4 EtOH ( 1 : 3 : 1.3 ) -78°C, THF 73% 84% e.e. 83% e.e. (R) * 72% * t-BuOH replacing EtOH Soai, Chem. Commun. 1987, 801; Chem. Commun. 1986, 1018 Brown, J. Am. Chem. Soc. 1988, 110, 1539 Brown, J. Org. Chem. 1988, 53, 1231 Brown, J. Org. Chem. 1986, 51, 1934 Miscellaneous Chiral Borohydride Reagents 86 - 98% e.e. R = alkyl, aryl THF, -78°C 75 - 85% 97% e.e. 87% e.e. 92% e.e. R = t-Bu = i-Pr = Et THF, -78°C 90 - 95% K - + Brown, Tetrahedron Let. 1991, 32, 6691 Ketone Rxn time (THF, -25°C) % Conv. % ee Brown, J. Org. Chem. 1989, 54, 4504 % Conv. % ee Rxn time Ketone (THF, 23°C) acetophenone 3-methyl-2-butanone cyclohexyl methyl ketone 2,2-dimethylcyclopentanone trans-4-phenyl-3-buten-2-one 2-cyclohexenone 4-phenyl-3-butyn-2-one 24 h 2 d 3 d 24 h 14d 7 d 5 h 80% 65% 65% 80% 60% 60% 82% >99% 95% 97% >99% 82% 74% 33% 2 Improved Enantioselectivity with Alphatic Ketones 72% 88% 86% 76% 72% 79% 50% 100% 60% 30% 40% 50% 7 days 2 days 4 days 14 days 4 days 4 days acetophenone 3-methyl-2-butanone cyclohexyl methyl ketone cyclohexyl ethyl ketone cyclopentyl methyl ketone cyclohexenone D. A. Evans Enantioselective C=O Addition: Ketone Reduction-2 Chem 115 B Cl B O Cl tBu Bzl B O H O O O O O S Ph R O Ph R OH OEt R O O O OH R OEt S PhCOHN NHCOPh CO2H CO2H H H N Me O OH Me N Cl O OH Cl 19A-06-Asym Redn-2 1/19/00 1:48 PM
A. Evans Enantioselective C=O Addition: Corey-ltsuno Catalyst Chem 115 Discovery of a Catalytic Process Recent Review: Corey, E.J. and C J. Helal (1998) ion of carbonyl The compounds with chiral oxazaborolidine catalysts paradigm for Catalytic cycle =+8 enantioselective catalysis and a powerful new synthetic Angew. Chem. Int. Ed. engl37(15):1987-2012 OBH2 The stoichiometric Process: Itsuno 1983-1985 11=人 Chiral 30°C,10hr Boron Hydride (H-BXc) (H-BXc) R=n-Bu 100 %ee Itsuno. Chem. Commun. 19 itsuno, J. Org. Chem. 1984 Itsuno, J. Chem. Soc. Perkin Trans / 1985. 2615 a The Catalytic Process: Corey, 1987 B JAcs1987,109.5551 Corey,JOc1988,53,2861 Catalyst X-ray, Corey, Tet Let 1992, 33, 3429 athe Joc catalyst prep: Mathre, JOC 1993, 58, 799 lathe JOC 1991. 56 R=t-Bu 97%ee Review)Martens, Tetrahedron Asymmetry 1992, 3, 1475 R=C-C6H11 91%ee But how does it really work? 19A-07-Corey Cat 11/1/00 8:03 AM
(Review) Martens, Tertrahedron Asymmetry 1992, 3, 1475 97 % ee 97 % ee 91 % ee But how does it really work ? R = Ph, R = t-Bu, R = c-C6H11 BH3 – + BH3 R = H R = Me ■ The Catalytic Process: Corey, 1987 Itsuno, J. Chem. Soc. Perkin Trans I. 1985, 2615 Itsuno, J. Org. Chem. 1984, 49, 555 Itsuno, Chem. Commun. 1983, 469 ■ The Stoichiometric Process: Itsuno, 1983-1985 ( H –BXC ) 2 equiv BH3 30 °C, 10 hr Chiral Boron Hydride ( H –BXC ) R = Me, 94 % ee R = Et, 94 % ee R = n-Bu 100 % ee D. A. Evans Enantioselective C=O Addition: Corey-Itsuno Catalyst Chem 115 Discovery of a Catalytic Process (0.1 equiv) B B BH3 – + + – + – The Catalytic Cycle + – + Corey, JOC 1988, 53, 2861 Corey, JACS 1987, 109, 5551 Corey, JACS 1987, 109, 7925 Improved version Catalyst X-ray, Corey, Tet. Let 1992, 33, 3429 Mathre, JOC 1993, 58, 2880 catalyst prep: Mathre, JOC 1993, 58, 799 Mathre, JOC 1991, 56, 751 O H2B RL C H RS OBH2 O H2B H N C RL RS N B X Y X O B N O B Y O C RS X RL H2N Ph Ph OH Me2HC R O Ph Ph OH H R H H N N O Ph Ph B R B R O Ph Ph H3B Me O R H R OH Me O Y O X B N Y C RS RL H BH3 N B O Ph B O Me Ph H H H X Ph B Me N O Ph Ph H Recent Review: Corey, E. J. and C. J. Helal (1998). “Reduction of carbonyl compounds with chiral oxazaborolidine catalysts: A new paradigm for enantioselective catalysis and a powerful new synthetic method.” Angew. Chem., Int. Ed. Engl. 37(15): 1987-2012. 19A-07-Corey Cat 11/1/00 8:03 AM
A. Evans Enantioselective C=O Addition: Catalyst Scope Chem 115 Representative Reduction The catalyst (R)cat (0. 2 equiv) (S)cat(0.1 equiv) 1.5 equiv HO 92%ee n-C5Hl1 ret.Let1992.33,2319 n-CsHl1 THF 23%C 2 min Arco Fluoxetine( Prozac) Synthesis (R)-cat, as above 94%ee>99‰) Corey,JAcs1987,109,7925 0. 1 equiv Tet Let1989,30.5207 Prozac③ i An a-Amino Acid Synthesis 91%ee nC5H1195% c-C6H1192% t-C4Hg 98% (S) 0. 1 equiv n-Bu Corey,JAcs1992,114,1906 Tet.Let1992,33,3435 Tet. Let1992,33,3431 CCl3 N3 m temp 19A-08-Corey Cat 1/19/00 1: 48 PM
D. A. Evans Enantioselective C=O Addition: Catalyst Scope Chem 115 Representative Reductions 90 : 10 91 : 9 (R)-cat, as above (S) cat (0.1 equiv) BH3 (0.6 equiv) THF 23°C, 2 min The catalyst Corey, JACS 1987, 109, 7925 (S) cat BH3 86% ee 91% ee BH3 (S) cat 91% ee BH3 (S) cat (R) cat (0.2 equiv) 1.5 equiv 92% ee Tet. Let 1992, 33, 2319 Fluoxetine (Prozac®) Synthesis BH3 94% ee (>99%) 0.1 equiv Na –I MeNH2 NaH Prozac® An α-Amino Acid Synthesis Tet. Let 1989, 30, 5207 0.1 equiv R ee n-C5H11 95% c-C6H11 92% t-C4H9 98% HO– N3 – rm temp Corey, JACS 1992, 114, 1906 Tet. Let 1992, 33, 3435 Tet. Let 1992, 33, 3431 Me Me O Me Me Me Me Me Me Me Me Me N B O Ph Ph H Me O O n-C5H11 O ArCOO ArCOO OH n-C5H11 O O Me Me Me HO Me Me O BH O F F Cl O N O O n-C5H11 OH ArCOO O OH Br O OH Br Me O OH Me B O Ph Ph H Me OH Cl NHMe OH O NHMe CF3 CF3 Cl CCl R 3 O OH R CCl3 B n-Bu H Ph Ph N O O BH O CCl R 3 OH N3 R COOH 19A-08-Corey Cat 1/19/00 1:48 PM
