1,5-asymmetric induction in boron-mediated beta-alkoxy methyl ketone aldol addition reactions.
This article presents studies that illustrate beta-alkoxy methyl ketone-derived boron enolates undergo diastereoselective aldol addition to afford the 1,5-anti diol relationship. The stereochemical outcome of this reaction is documented to be general for a variety of beta-alkoxy methyl ketone analogues and aldehyde partners. The double stereodifferentiating reactions of these enolates with chiral beta-alkoxy aldehydes have also been investigated in conjunction with the possibility of controlling the absolute stereochemistry of the aldol process. With the proper selection of reaction conditions, the proximal alkoxy substituent on either the aldehyde (1,3-induction) or the enolate fragment (1,5-induction) can be employed to control facial selectivity of the aldol addition. Selection of a boron enolate ensures dominant 1,5-anti induction from the beta-alkoxy methyl ketone-derived enolate partner while negating any influence of the beta-alkoxy aldehyde substituent. Conversely, if stereochemical control from the beta-alkoxy aldehyde is desired, a Lewis acid-catalyzed enolsilane addition ensures dominant 1,3-induction from the aldehyde beta-oxygen substituent.
Evans
David A
DA
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA. Evans@chemistry.harvard.edu
Côté
Bernard
B
Coleman
Paul J
PJ
Connell
Brian T
BT
D000438:Alcohols / Q000138:chemical synthesis*; D001895:Boron / Q000737:chemistry*; D004987:Ethers / Q000138:chemical synthesis / Q000737:chemistry*; D007659:Ketones / Q000138:chemical synthesis / Q000737:chemistry*; D007700:Kinetics; D013237:Stereoisomerism; D013696:Temperature
D000438:Alcohols; D004987:Ethers; D007659:Ketones; D001895:Boron