Work

Direct Asymmetric anti-Mannich-Type Reactions Catalyzed by a Designed Amino Acid

Year: 2006

Type: article

Abstract: The development of catalysts for Mannich-type reactions that afford anti-products with excellent diastereo- and enantioselectivities under mild conditions and low catalyst loadings (1-5 mol %) is reported. Based on principles gained from the study of (S)-proline-catalyzed Mannich-type reactions that afford enantiomerically enriched syn-products, (3R,5R)-5-methyl-3-pyrrolidinecarboxylic acid (RR35) has been designed to catalyze the direct enantioselective anti-selective Mannich-type reactions. Computational studies of the above reaction using HF/6-31G* level of theory suggested that this design would be highly effective. The catalyst was subsequently synthesized and studied in organocatalytic Mannich-type reactions between unmodified aldehydes and N-PMP-protected alpha-imino esters. In accord with the design principles and in quantitative agreement with the theoretical predictions, reactions catalyzed by this catalyst afforded anti-products in good yields with excellent diastereo- and enantioselectivities (anti:syn 94:6 to 98:2, >97 to >99% ee).

Source: Journal of the American Chemical Society

DOI: 10.1021/ja056984f

Authors: Susumu Mitsumori, Haile Zhang, Paul Ha-Yeon Cheong, K. N. Houk, Fujie Tanaka, Carlos F. Barbas

Institutions: Scripps Research Institute, University of California, Los Angeles

Language: English

Topic: Asymmetric Synthesis and Catalysis

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: green

Funder: National Institute of General Medical Sciences

Awards: G2679848640, Stereoselectivities of Synthetic Organic Reactions, STEREOSELECTIVITIES IN SYNTHETIC ORGANIC REACTIONS