D.A. Evans Enolate Alkylation: Stereoelectronic Control Elements Chem 206 Review Evans, D. A. Stereoselective Alkylation Reactions of Chiral/ Metal Enolates; Morrison, J D, Ed. AP: New York, 1984: Vol 3, pp 1-110 Examples where stereoelectronic factors are dominant Stereoelectronic Issues I Enolization: Breaking C-H bond must overlap with *C-O in TS# Alkylation: Forming C-El bond must overlap with T*C-O in TS+ LDA o NMe R-x 0 Bn-Br >99 Issue: Degree of rehybridization ood illustration of the impact of allylic strain in TS+? 日 BOC-N- R R-x a Cyclohexanone Enolate The C19 Angular Methyl Group in the steroid nucleus path A e3C LI/NH3 chair conformation Me- pathE Me3C R twistboat conformation Metal R-substituent Electrophile Ratio. a:e CD3l 70:30 83:17 Chair vs boat geometries not stongly reflected in diastereomeric TS*s.The The enolate(Chem 3D) transition states is early and enolate-likeN Boc O Me C C O R H R M H M O C H R C R El H Me3C R O C C O R R H M El C C O R El R M H Me3C H R O El El O Me3C H R C C R OLi H Me3C N O H H Me H O RO O Me OH H H Me O O Li CO2Me Me-I Li Me CD3I R–X Me-I N C C LiO H Me H Boc R–X N Boc O Me R R–X Allyl–Br Bn–Br LiO Me OH H H R H O Me OH H H R H Me N O H R Me H O RO Me-I path A ■ Cyclohexanone Enolate: Chair vs boat geometries not stongly reflected in diastereomeric TS‡s. The transition states is early and enolate-like. 83:17 Metal 70:30 R-substituent Electrophile Ratio, a:e twist boat conformation chair conformation ‡ e El(+) e El(+) Issue: Degree of rehybridization in TS‡? ■ Alkylation: Forming C–El bond must overlap with p* C–O in TS‡ ■ Enolization: Breaking C–H bond must overlap with p* C–O in TS‡ El(+) base Stereoelectronic Issues D. A. Evans Enolate Alkylation: Stereoelectronic Control Elements Chem 206 a Evans, D. A. Stereoselective Alkylation Reactions of Chiral Metal Enolates.; Morrison, J. D., Ed.; AP: New York, 1984; Vol. 3, pp 1-110. Review path E LDA ratio >99:1 93:7 Pilli, Tetrahedron, 1999, 55, 13321 Examples where stereoelectronic factors are dominant good illustration of the impact of allylic strain Li/NH3 (90%) one isomer The C19 Angular Methyl Group in the steroid nucleus The enolate (Chem 3D) LDA favored disfavored