D. A. Evans, D. H. Ripin The Aldol Reaction: Metal-Centered Chirality Chem 206 Masamune-Reetz Analogy Chiral Anti Aldol Reaction: JACS 1990.112. 4977: TL 1991. 32. 2857 o'Bu R RCHO Me' SCEt3 一( syn anti%eYed Ph-Me2:989493% 6:947582% Metal-Based Chiral Auxilliary Ph-Br2:989686% 多 111,5494 112.4977 chex. Br2:989165% Bro o a Chiral Syn Aldol Reaction JACS 1989, 111, 5494 enolization Does this reagent perform in accord with the Masamune- Reetz analogy? Note: The sulfonamide nitrogens are pseudo-tetrahedt Me Me rcho 94:69786% Either enolate geometry possible with proper choice of base, solvent, and substrate Me2CH- R2 1, Triethylamine MeCH2 68% tUo PhCH3/Hexane Buo Chiral Acetate Aldol Reaction JACS 1989. 111. 5494 1. Hunig's Base LB R2 enolization SPh RCHO CH2Cl2-78C A mechanistic proposal for enolization control is presented in paper Ph-9184% (Corey) JACS. 1989, 111, 5494 Me2CH8382%MeCH2- Me2CH- (R) (R) Me2CH- (R) Br Me (X) (X) (R) Ph- 94 : 6 Yield Ratio syn:anti 86 % 91 % 68 % 98 : 2 >98 : 2 % ee 97 95 >98 83 91 % ee 82 % 84 % Yield Ph￾Br 91 96 % ee 2 : 98 65 % 86 % chex￾Ratio syn:anti Yield Ph- 2 : 98 Me Ph- 2 : 98 Yield Ratio syn:anti chex- 93 % 6 : 94 82 % % ee 94 75 O SCEt3 B Me R R N B N S S O O Br O O CF3 F3C CF3 CF3 Ph Ph RCHO O tBuO Me O Me PhS R R S R H R H Me B O O PhS Me O B *R2 Me tBuO O B *R2 HO Me R SCEt3 O Me Me O X O tBu O O Me SPh RCHO RCHO RCHO O O t R Bu X HO R OH SPh O O Me OH Me R D. A. Evans, D. H. Ripin The Aldol Reaction: Metal-Centered Chirality Chem 206 favored Masamune-Reetz Analogy: ■ Metal-Based Chiral Auxilliary: 1 References: (Corey) JACS. 1989,111, 5494 (Corey) JACS. 1990,112, 4977 (Corey) TL. 1991,32, 2857 (Corey) TL. 1993,34, 1737. 1, Triethylamine ■ Enolization: 1, Hunig's Base Either enolate geometry possible with proper choice of base, solvent, and substrate. A mechanistic proposal for enolization control is presented in paper (Corey) JACS. 1989,111, 5494 enolization ■ Chiral Acetate Aldol Reaction JACS 1989,111, 5494. ■ Chiral Anti Aldol Reaction: JACS 1990,112, 4977; TL 1991,32, 2857. ■ Chiral Syn Aldol Reaction JACS 1989,111, 5494. Does this reagent perform in accord with the Masamune-Reetz analogy? Note: The sulfonamide nitrogens are pseudo-tetrahedral enolization enolization PhCH3 / Hexane -78˚C CH2Cl2 -78˚C