Organocatalytic Asymmetric Addition of Alcohols and Thiols to Activated Electrophiles: Efficient Dynamic Kinetic Resolution and Desymmetrization Protocols

• Published in: Journal of organic chemistry Vol. 73; no. 16; pp. 6409 - 6412
• Main Authors: Peschiulli, Aldo, Quigley, Cormac, Tallon, Seán, Gun’ko, Yuri K, Connon, Stephen J
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 15-08-2008
• Subjects: Alanine - analogs & derivatives; Alanine - chemistry; Alcohols - chemistry; Aliphatic compounds; Amino Acids - chemistry; Anhydrides - chemistry; Catalysis; Catalysts: preparations and properties; Chemistry; Cinchona Alkaloids - chemistry; Exact sciences and technology; General and physical chemistry; Heterocyclic compounds; Kinetics; Lactones - chemistry; Organic chemistry; Preparations and properties; Propanols - chemistry; Sulfhydryl Compounds - chemistry; Theory of reactions, general kinetics. Catalysis. Nomenclature, chemical documentation, computer chemistry; Urea - analogs & derivatives; Valine - analogs & derivatives; Quinuclidine derivatives; Enantioselectivity; Nitrogen heterocycle; Thiolysis; Alcohol; Oxygen heterocycle; Organic sulfide; Alkaloid; Asymmetric synthesis; Ureas; Chemical synthesis; Oxazole derivatives; Electrophile; Oxygen nitrogen heterocycle; Alanine; Thiol; Phenylalanine; Bifunctional compound; Methionine; Quinoline derivatives; Steric hindrance; Lactone; Sulfur containing aminoacid; α-Aminoacid; Optical resolution; Catalyst; Nucleophile
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo801158g

Bifunctional urea-based cinchona alkaloid derivatives have been shown to promote highly efficient DKR reactions of azalactones using an alcohol nucleophile. The optimum catalyst is remarkably insensitive to the steric bulk of the amino acid residue, allowing alanine-, methionine-, and phenylalanine-derived azalactones to undergo DKR with unprecedented levels of enantioselectivity using a synthetic catalyst. The first DKR of these substrates by thiols and the highly enantioselective desymmetrization of a meso-glutaric anhydride by thiolysis are also reported.