An Asymmetric, Bifunctional Catalytic Approach to Non-Natural α-Amino Acid Derivatives

• Published in: Journal of organic chemistry 2007-07, Vol.72 (14), p.5380-5382
• Main Authors: Paull, Daniel H, Alden-Danforth, Ethan, Wolfer, Jamison, Dogo-Isonagie, Cajetan, Abraham, Ciby J, Lectka, Thomas
• Format: Article
• Language: English
• Subjects: Amino Acids - chemical synthesis; Amino Acids - chemistry; Biological Products - chemistry; Catalysis; Catalytic reactions; Chemistry; Exact sciences and technology; General and physical chemistry; Kinetics and mechanisms; Metals - chemistry; Molecular Structure; Noncondensed benzenic compounds; Organic chemistry; Preparations and properties; Reactivity and mechanisms; Stereoisomerism; Theory of reactions, general kinetics. Catalysis. Nomenclature, chemical documentation, computer chemistry
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo070472x

A catalytic, asymmetric process for the synthesis of 1,4-benzoxazinones from o-benzoquinone imides and ketene enolates is reported. Addition of Lewis acids (Zn(OTf)2, In(OTf)3, and in particular Sc(OTf)3) creates a bifunctional catalytic system that dramatically increases the reaction rate and the yield of these non-natural amino acid precursors while preserving the remarkable enantioselectivity inherent to the reaction. Cocatalyst Sc(OTf)3 increases the yield by up to 42% while producing products in >99% ee.