Scope and Mechanism of Tandem Aza-Michael Reaction/Enantioselective Protonation Using a Pd-μ-Hydroxo Complex under Mild Conditions Buffered with Amine Salts

• Published in: Chemistry, an Asian journal an Asian journal, 2011-02, Vol.6 (2), p.658-668
• Main Authors: Hamashima, Yoshitaka, Suzuki, Shoko, Tamura, Toshihiro, Somei, Hidenori, Sodeoka, Mikiko
• Format: Article
• Language: English
• Subjects: Amines - chemistry; amino acids; Amino Acids - chemical synthesis; Amino Acids - chemistry; asymmetric catalysis; Chemistry; Hydrogenation; Michael addition; palladium; Palladium - chemistry; protonation; Protons; Salts - chemistry; Stereoisomerism
• ISSN: 1861-4728; 1861-471X
• DOI: 10.1002/asia.201000740

The tandem aza‐Michael reaction/enantioselective protonation of α‐substituted α,β‐unsaturated carbonyl compounds is described in detail. The key to success is the combined use of a Brønsted basic palladium–μ‐hydroxo complex and amine salts, which allows for the controlled generation of active catalyst and nucleophilic free amines. This catalytic system was applicable to various acceptors and aromatic amines, and the desired β‐amino acid derivatives with a chiral center at the α position were produced in good yield with excellent enantioselectivity (up to 98 % ee). For electron‐deficient amines, the introduction of free amine as an additive was effective in promoting the reaction. The results of mechanistic studies, including determination of the absolute configuration of the product, are discussed. Salt‐controlled reaction: The tandem aza‐Michael reaction/enantioselective protonation of α‐substituted α,β‐unsaturated carbonyl compounds is described in detail. The combined use of chiral palladium complex 1 and amine salts was critical to obtain α‐substituted β‐amino carbonyl compounds with high enantioselectivity (see scheme).