D. A. Evans The Aldol Reaction: Syn Aldol Rxns of Chiral Ethyl Ketones Chem 206 General Reaction for Syn Aldols: M=B, Ti n-Bu2BOTf RCHO M=B Ti R-CH TBSO TBSo Me TBS= SIMe2 Bu The Transition States 973 R Masamune. JACS 1981. 103.15 Me RCHO L\ 982 BnOCH2 CH2 96: 4 Me2CH RL Me L2BOTf Me PT2NEt RCHO Me me Diastereoselection Evans,JAcS1991,113,1047 This system does not give a completely 63:37-84:16 clean(Z) enolate Examples 17-85:15 ()-lpc Bu2BOTf BuMe2Si PInET BuM Paterson, McClure, Tet. Lett. 1987. 28, 1229. (++-lpc 91: 9-94: 6 Enders aclEE 1988 27. 581 Diastereoselection 96-98% TBSo O OH MeMe Me Me? CHCHO TBSQ O TBSo O OH TBS Evans,JAcS1991,113,1047 Diastereoselection: 99: 1(81%) Evans, JACS 1991. 113. 104 Diastereoselection: 95: 5 (80-90%)RM H RL C H R H Me O O M L L O M O C H Me H R RM H RL L L ‡ ‡ O M RL RM Me O Me RM RL M O Me RM RL M R-CHO Me OH R R L RM O RL R RM Me O OH O OH RM Me R RL Me R 1 O Me TBSO TBSO O Me R3N RCHO n-Bu2BOTf tBuMe2Si Me O Me Me O tBuMe2Si R Me OH TBSO Me O Me Me Me Me Me Me O Me TBSO TBSO O Me OH Me Me Me O TBSO Me2CHCHO TiCl4 EtNiPr2 TiCl4 EtNiPr2 Me2CHCHO RCHO RCHO Me2CHCHO TiCl4 EtNiPr2 R OH Me R O TBSO TBSO Me O R 1 R Me OH Ph Et BnOCH2CH2 Me2CH OH Me O Me TBSO Me Me Me Me Me Me Me Me TBSO Me O Me OH Evans, JACS 1991, 113, 1047. Diastereoselection: 95:5 (80-90%) This system does not give a completely clean (Z) enolate 63:37 - 84:16 83:17 - 85:15 72:28 91:9 - 94:6 Bu 9-BBN (-)-Ipc Paterson, McClure, Tet.Lett. 1987, 28, 1229. (+)-Ipc L2BOTf iPr2NEt Enders ACIEE 1988, 27, 581. Diastereoselection = 96-98% Bu2BOTf, iPr2NEt Examples: General Reaction for Syn Aldols: M = B, Ti D. A. Evans The Aldol Reaction: Syn Aldol Rxns of Chiral Ethyl Ketones Chem 206 L Diastereoselection Evans, JACS 1991, 113, 1047. RCHO disfavored favored RCHO The Transition States: Evans, JACS 1991, 113, 1047. Diastereoselection: 99:1 (81%) Masamune, JACS 1981, 103, 1566. 97:3 98:2 96:4 >99:<1 TBS = SiMe2 tBu Diastereoselection M = B, Ti