Visible-Light-Enabled Dual-Catalysis Approach to Stereoselective [2 + 2] Cycloaddition of Erlenmeyer-Plöchl Azlactones

Abstract

Visible-light-driven dual catalysis was employed to stereoselectively produce densely substituted cyclobutanes from Erlenmeyer-Plöchl azlactones. The single-step preparation of non-natural amino acid dimers containing the cyclobutane moiety was achieved through a synergy between iridium photocatalysis and catalytic nickel(II) triflate as a Lewis acid. The desired 1,2-(zeta)-Z,E-isomers were isolated in good yields and with high regio- and diastereoselectivity (in all cases, >19:1 d.r.). To the best of our knowledge, this is the first report of direct access to truxinic acid analogues using azlactones. Control experiments, EPR reaction monitoring, and DFT calculations suggest that the presence of a Lewis acid, combined with the use of powerful blue LEDs, plays a crucial role in the reactivity of this reaction.