D. A. Evans The Aldol reaction Boron enolates Chem 206 Why Boron? Are(E)enolates intrinsically less diastereoselective? M-0→B0MC→BC Design TS where control can come 1.9-2.2A 1.4-1.5A 2.0-2.2A 1.5-1.6A Now that there are good methods for preparing(E) enolates Dialkylboron chlorides(Brown) exclusively from metal center it appears that both enolate geometries are nearly equivalent /ACS. 1989, 111, 3441-3442 0 OH R2CHO Acs.1989,11,3441-3442 Jorg.chem.199358,147-153 Me Chx2BCI HcHO favored syn diastereomer 99% 95% anti RaCHO 9-BBN-CI OB-9-BBN anti diastereomer 98% syn X= CMe3 M=U >98: 2 Heathcock 1977 It appears that there is not a great difference in aldol diastereoselectivity DuBois 1972 M=BBu2 >97: 3 DuBois 1972 Dissection of the Aldol problem: Selection of one enantioface X= C6H5 M=Li 80:20 0 Evans. Masamune. 1979-81 X=Et 80:20 =BBu2>97 HR 48:52 House1971 M=BBu2 33: 67(ether) r diastereomers M=BCy(thex) 6: 94(CH 2C12)I Evans/masamune, 1979-81 Control attack on the two enolate enantiofaces E(+) M=B(Cyp)2 <5: 95(pentane 0-+M Evans et al.JAcs1979,101,61206123;JACS1981,103,3099-3111 Masamune,Tet.Lett1979,1665,2225,229,3937 Relevant stereochemical inform E(+) ould be included in either XPh O Me Ph OH OH Ph Me O Ph El X Me O PhCHO PhCHO OH R Me X O O X Me R OH OBChx2 Ph Me Me Ph OB-9-BBN O X Me R OH OH R Me X O O M Me H X 9-BBN-Cl Et3N Et2O H R O O Ph Me O Me X El O Me X M O M X Me M–C B–C R2 OH X O Me Me O X OH R2 M–O B–O O C O B H L L R2 X Me H C H Me X H B L L O O R2 O M O M (t)BuS Me R2CHO R2CHO Me X O BL2 D. A. Evans The Aldol Reaction: Boron Enolates Chem 206 Evans et al. JACS 1979, 101, 6120-6123; JACS 1981, 103, 3099-3111 anti diastereomer favored ‡ syn diastereomer ‡ Why Boron? 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 disfavored M = BBu2 > 97 : 3 DuBois 1972 M = BBu2 > 97 : 3 M = BBu2 > 97 : 3 X = Et M = Li 80 : 20 Yamamoto 1977 M = BBu2 33 : 67 (ether) M = BBu 17 : 83 (pentane) 2 M = BCy(thex) 6 : 94 (CH2Cl2 ) M = B(Cyp)2 <5 : 95 (pentane) 1.9-2.2 Å 1.4-1.5 Å 2.0-2.2 Å 1.5-1.6 Å To tighten up the transition state. Design TS where control can come exclusively from metal center Masamune, Tet. Lett 1979, 1665, 2225, 2229, 3937 Are (E) enolates intrinsically less diastereoselective? Now that there are good methods for preparing (E) enolates, it appears that both enolate geometries are nearly equivalent. Dialkylboron chlorides (Brown) JACS. 1989, 111, 3441-3442. J. Org. Chem. 1992, 57, 499-504. J. Org. Chem. 1992, 57, 2716-2721. J. Org. Chem. 1992, 57, 3767-3772. J. Org. Chem. 1993, 58, 147-153. Chx2BCl JACS. 1989, 111, 3441-3442. ~99% (E) 95% anti ~99% (Z) 98% syn DIPEA Et2O It appears that there is not a great difference in aldol diastereoselectivity Dissection of the Aldol Problem: Selection of one enantioface anti diastereomers syn diastereomers Relevant stereochemical information could be included in either X or M Control attack on the two enolate enantiofaces El(+) El(+) Evans, Masamune, 1979-81 Evans/masamune, 1979-81