Bifuctional Amino-Squaramides Catalyzed Asymmetric Spiroannulation Cascades with Aliphatic β,γ-Unsaturated α-Keto Esters: Controlling an Aldehyde Enolate

• Published in: Journal of organic chemistry Vol. 77; no. 6; pp. 2959 - 2965
• Main Authors: Wang, Xiaoqin, Yao, Weijun, Yao, Zhihui, Ma, Cheng
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 16-03-2012
• Subjects: Aldehydes - chemistry; Aliphatic compounds; Amides - chemistry; Catalysis; Catalysts: preparations and properties; Chemistry; Esters; Exact sciences and technology; General and physical chemistry; Heterocyclic compounds; Heterocyclic compounds with o, s, se, te hetero atom and condensed derivatives; Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings; Organic chemistry; Preparations and properties; Pyrans - chemistry; Stereoisomerism; Theory of reactions, general kinetics. Catalysis. Nomenclature, chemical documentation, computer chemistry; Nitrogen heterocycle; Chiral compound; Selectivity; Stereochemistry; Oxygen heterocycle; Unsaturated compound; Stereoselectivity; Amine; Asymmetric synthesis; Acetalization; Aromatic compound; Michael addition; Catalytic reaction; Aliphatic compound; Pyran derivatives; Hemiacetal; Aldehyde; Ketone; Spiran; Annelation; Cyclic compound; Ketoester; Enolate; Catalyst; Successive reaction
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo202633c

A quinidine-derived squaramide Ib catalyzed cyclization reaction of β-oxo aldehydes 1 and aliphatic or aromatic β,γ-unsaturated α-keto ester 2 is described. Using cyclic aldehyde substrates, this procedure provided a promising approach to a variety of spiro-3,4-dihydropyrans bearing three continuous quaternary and tertiary stereocenters in moderate to good yield with high stereoselectivities. Substituents on the nitrogen atoms of the squaramide moiety of the catalyst proved crucial to the reaction outcome. The stereochemistry of the three newly formed chiral centers (trans-selective) of the major product indicates a Micheal addition/hemiacetalization domino sequence for the present annulations.