Helical-Peptide-Catalyzed Enantioselective Michael Addition Reactions and Their Mechanistic Insights
2016
Ueda, Atsushi | Umeno, Tomohiro | Doi, Mitsunobu | Akagawa, Kengo | Kudo, Kazuaki | Tanaka, Masakazu
Helical peptide foldamer catalyzed Michael addition reactions of nitroalkane or dialkyl malonate to α,β-unsaturated ketones are reported along with the mechanistic considerations of the enantio-induction. A wide variety of α,β-unsaturated ketones, including β-aryl, β-alkyl enones, and cyclic enones, were found to be catalyzed by the helical peptide to give Michael adducts with high enantioselectivities (up to 99%). On the basis of X-ray crystallographic analysis and depsipeptide study, the amide protons, N(2)–H and N(3)–H, at the N terminus in the α-helical peptide catalyst were crucial for activating Michael donors, while the N-terminal primary amine activated Michael acceptors through the formation of iminium ion intermediates.
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