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 PMMgX 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