Direct Mannich-Type Reactions Promoted by Frustrated Lewis Acid/Brønsted Base Catalysts

• Published in: Angewandte Chemie International Edition Vol. 55; no. 44; pp. 13877 - 13881
• Main Authors: Chan, Jessica Z., Yao, Wenzhi, Hastings, Brian T., Lok, Charles K., Wasa, Masayuki
• Format: Journal Article
• Language: English
• Published: WEINHEIM Blackwell Publishing Ltd 24.10.2016; Wiley; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: acid-base catalysis; boron; Carbonyl compounds; Carbonyls; Catalysts; Chemistry; Chemistry, Multidisciplinary; Esters; frustrated Lewis pairs; Lewis acid; Lewis acids; Mannich-type reactions; Physical Sciences; Science & Technology; Selectivity; ASYMMETRIC CATALYSIS; HYDROGENATION; IMINES; acid-base catalysis; HYDROSILYLATION; Lewis acids; Mannich-type reactions; H BOND ACTIVATION; REDUCTION; ALDOL REACTION; BETA-AMINO; boron; BORYLATION; frustrated Lewis pairs; PAIRS
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201608583

Direct Mannich‐type reactions that afford both α‐ and β‐amino esters by the reaction of a broad range of carbonyl compounds and aldimines are disclosed. The transformation is promoted by a sterically frustrated Lewis acid/Brønsted base pair, which is proposed to operate cooperatively: Within the catalyst complex, an enolate is generated that then reacts with a hydrogen‐bond‐activated imine. Noncovalent interactions between reactants and the catalyst provide selectivity and new opportunities for future catalyst design. It pays to be direct if you're frustrated: A sterically frustrated Lewis acid/Brønsted base pair was found to serve as a potent cooperative acid/base catalyst for direct Mannich‐type reactions (see scheme; EDG=electron‐donating group, PG=protecting group). An array of ketone, ester, amide, and thioester pronucleophiles underwent enolization by the catalyst and reaction with aldimines to afford both α‐ and β‐amino esters.