Carbene-catalyzed enantioselective seleno-Michael addition as access to antimicrobial active Se-containing heterocycles

Abstract

Organoseleniums exhibit a diverse set of biological activities that are pivotal for drug discovery and are widely explored in synthetic chemistry and material science. While many transformations have been developed for non-enantioselective C–Se bond formations, the catalyst-controlled stereoselective preparation of chiral organoseleniums continues to be of considerable challenge. In particular, there are limited studies on the enantioselective seleno-Michael addition reactions to access chiral selenium functional molecules. Here, we disclose a carbene-catalyzed highly enantioselective nucleophilic C–Se bond construction through formal [3 + 3] annulations between selenocarboxamides and bromoenals, affording seleno-thiazinone products with good yields and excellent enantioselectivities. The choice of a weak inorganic base was pivotal to suppressing the unproductive racemization and decomposition of the selenium products. Notably, the catalytically generated chiral selenium-containing heterocyclic products feature remarkable antimicrobial activities that could serve as promising lead scaffolds for further agrochemical development.