D A. Evans Enantioselective C=O Addition: Noyori Catalyst Chem 206 Catalytic Asymmetric Carbonyl Addition The Catalytic Cycle eplace with chiral controller N-Me N-Me loyori& co-workers, J. Am. Chem. Soc 111.4028 Review Noyori Angew. Chem. Int. Ed. 1991, 30, 49 Review: L Pu. Chem. Reviews 2001. 101. 757-824 Zn -Et 9098%ee HcHO Me RDS H the catalyst Ar-CHO R 2 Zn 0°c, toluene 59-97% C6H5CHO Et2zn 98%ee. I Catalyst must be sterically hindered so that association is precluded 91% Et2Zn 93%ee. Et2 p-MeOC6H4CHo Et2Zn 93%ee PhcH2 CH2CHO Et2Zn 90%ee. R n-C6H13CHO 61%ee. 4 R O--ZnR The method is catalytic in aminoalcohol. a Two zinc species per aldehyde are involved in the alkylation step R-0—2n-R a Product is taken out of the picture by aggregationEt2Zn Me Me N H Me Me Me O Zn H Et O C H Zn Et Et C O H Zn Et H H O N Me Me Me Me Me RDS O C H O Et H Zn–Et R' O Zn O Zn Zn O O Zn R R R R' R' R' R Zn R' O R O R' Zn R O Zn Zn O R R' R' R Me Me N H Me Me Me O Zn H Et Zn Et C Et O H O Zn Et H H N Me Me Me Me Me R'O ZnR Ar R’ OH Me Me N H Me Me Me O Zn H Et PhCHO Me2Zn Et2Zn Me2Zn Et2Zn Et2Zn Et2Zn Et2Zn Et2Zn Zn R Zn I I C O R R H (DAIB-Zn) Review: Noyori Angew. Chem. Int. Ed. 1991, 30, 49 Review: L. Pu, Chem. Reviews 2001, 101, 757-824 ■ 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 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. 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 90-98% ee The Catalytic Cycle Chem 206