title: Highly enantioselective aldol reactions between acetaldehyde and activated acyclic ketones catalyzed by chiral primary amines.
abstract: Highly enantioselective cross-aldol reactions between acetaldehyde and activated acyclic ketones are reported for the first time. Various acyclic ketones, such as saturated and unsaturated keto esters, reacted with acetaldehyde in the presence of a chiral primary amine and a Brønsted acid to afford optically enriched tertiary alcohols in good yields and with excellent enantioselectivities. Trifluoromethyl ketones were tolerable under the reaction conditions, thereby affording the trifluoromethyl carbinol in good-to-excellent yields and enantioselectivities. Structural modification of the chiral amines from the same chiral source switched the stereoselectivity of the products. The utility of aldol chemistry was demonstrated in the brief synthesis of functionally enriched δ-lactones. Theoretical calculations on the transition-state structure indicated that the protonated tertiary amine could effectively activate the carbonyl group of a keto ester to promote the addition process through hydrogen-bonding interaction and, simultaneously, provide an appropriate attacking pattern for the approach of the keto ester to the enamine, which is formed from acetaldehyde and the chiral catalyst, on a particular face, resulting in high enantioselectivity.
authors.affiliation: Chemical Synthesis and Pollution Control, Key Laboratory of Sichuan Province and College of Chemistry and Chemical Engineering, China West Normal University, Nanchong 637000, PR China.
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Deng
authors.forename: Jin-Quan
authors.initials: JQ
authors.lastname: Chen
authors.forename: Long
authors.initials: L
authors.lastname: He
authors.forename: Tai-Ran
authors.initials: TR
authors.lastname: Kang
authors.forename: Quan-Zhong
authors.initials: QZ
authors.lastname: Liu
authors.forename: Shi-Wei
authors.initials: SW
authors.lastname: Luo
authors.forename: Wei-Chen
authors.initials: WC
authors.lastname: Yuan