Highly Enantioselective Epoxidation of Trisubstituted Vinyl Sulfones with H2O2 Catalyzed by a Bioinspired Manganese Catalyst

Abstract

Chiral epoxysulfones are valuable yet challenging targets, particularly trisubstituted alkenyl sulfones, owing to their strong electron-withdrawing nature and large steric bulk. Herein, we describe the design and optimization of a proline-derived non-heme manganese catalyst, based on an established benzimidazole-containing N4 ligand platform, that employs H2O2 as a green terminal oxidant and enables the highly efficient asymmetric epoxidation of various alkenyl sulfones, including cyclic 2-arylbenzo[b]thiophene-1,1-dioxides and acyclic exocyclic α,β-unsaturated sulfones. Notably, the catalytic system is also compatible with structurally related non-sulfonyl substrates, such as 2-aryl-1H-inden-1-ones. Mechanistic studies support a high-valent MnV=O species as the active oxidant, and the p-methoxybenzyl pendant arm on the ligand significantly enhances stereoselectivity by remotely modulating the electronic properties of the metal center and the steric environment of the chiral pocket. This work establishes a sustainable and broadly applicable catalytic platform for the efficient synthesis of challenging chiral epoxide architectures that are difficult to access by conventional methods.