D A. Evans The Aldol Reaction: Early Contributions Chem 206 General Reviews of the aldol literature DuBois 1965-67: Rough correlation between enolate stucture product stereochemistry for alkali and alkaline earth enolates Mukaiyama in Organic Reactions, 1982; Vol 28, pp 203-331 o OH o OH Evans in Topics in Stereochemistry, 1982; Vol 13, pp 1-115 Heathcock in Asymmetric Synthesis, 1984: Vol 3, pp 111-212 Comprehensive Organic Synthesis, 1991: Vol 2 (E)Enolate anti diastereomers oup i& ll metal enolates: Heath Group Ill metal enolates: Masamune 17,pp239 o OH Transition metal enolates: Paterson: Chapter 1.9, pp 30 Control relative stereochemical relationships (Z) Enolate syn diastereomers Zimmerman 1957: Zimmerman-Traxler Model for(4) Enolates Proposed chair-like geometry for the Ivanov Reaction X OM OMaX 丰 HcHO - MgBr MgBr R2 R2 OH O R2CHO Me H syn: anti anti diastereomer M=Li >98: 2 Heathcock 1977 Zimmerman recognized that diastereoselection should be a function of the X=CE3 1 M=MgBr >95: 5 DuBois 1972 relative sizes of the substituents on the carbonyl component. He also speculated on the role that the metal center might play in controlling The onby flaw in the study was that he failed to determine whether the aldol M=AlEt2 50: 50 House 1971 dducts were stable to the reaction condition Zimmerman J. Am. Chem. Soc 1956, 79, 1920 Stereocontrol optimal for " large"X; the reaction is not generalRough correlation between enolate stucture & product stereochemistry for alkali and alkaline earth enolates DuBois 1965-67: Stereocontrol optimal for "large" X; the reaction is not general. OMgBr OMgBr Ph O MgBr O H Ph OMgX Ph H H Ph OMgX H O Ph MgBr O O Me X M O M X Me R2CHO Ph OH O O OH Ph Ph OH OH Ph Ph OH O Me X O M O M i-PrMgBr PhCHO H3O + R2CHO H R O O H R C H Me X H M L L O O R2 O C O M H L L R2 X Me H O X Me R OH OH R Me X O Me O X OH R2 R2 OH X O Me OH R Me X O O X Me R OH Mukaiyama in Organic Reactions, 1982; Vol 28, pp 203-331 D. A. Evans The Aldol Reaction: Early Contributions Chem 206 General Reviews of the Aldol Literature: Evans in Topics in Stereochemistry, 1982; Vol 13, pp 1-115 Heathcock in Asymmetric Synthesis, 1984; Vol 3, pp 111-212 Comprehensive Organic Synthesis, 1991; Vol 2 Group I & II metal enolates: Heathcock; Chapter 1.6, pp 181 Group III metal enolates: Masamune; Chapter 1.7, pp 239 Transition metal enolates: Paterson; Chapter 1.9, pp 301 (Z) Enolate (E) Enolate anti diastereomers Control relative stereochemical relationships syn diastereomers Zimmerman 1957: Proposed chair-like geometry for the Ivanov Reaction ratio, 75:25 ‡ ‡ Zimmerman recognized that diastereoselection should be a function of the relative sizes of the substituents on the carbonyl component. He also speculated on the role that the metal center might play in controlling the process. The only flaw in the study was that he failed to determine whether the aldol adducts were stable to the reaction conditions. Zimmerman, J. Am. Chem. Soc 1956, 79, 1920 anti diastereomer favored ‡ syn diastereomer ‡ Zimmerman-Traxler Model for (Z) Enolates syn:anti X = C6H5 X = CMe3 M = Li 48 : 52 M = Li > 98 : 2 M = MgBr > 95 : 5 M = Li 80 : 20 M = AlEt2 50 : 50 Heathcock 1977 DuBois 1972 House 1971