Organocatalytic enantioselective synthesis of S(IV)-stereogenic sulfinamides enabled by an air-stable chiral phosphine.

Enantioenriched vinyl sulfinamides with chiral-at-sulfur chirality are medicinally valuable but have limited accessibility with conventional strategies. Here we disclose an organocatalytic approach via enantioselective C-S bond formation between Morita-Baylis-Hillman esters and sulfinylamines catalysed by a designed chiral organophosphine. The structural rigidity of this catalyst is crucial for not only the excellent chemo-, enantio- and diastereoselectivities in this process but also its extraordinary air stability. Density functional theory and experimental studies indicated that the phosphonium species probably serves as the catalyst resting state, and the sulfinylamine may play a dual role as both reaction partner and promoter for the formation of the key phosphonium intermediate. The cyclic vinyl sulfinamides showed promising binding affinity to the mutant spike of severe acute respiratory syndrome coronavirus 2 and ENV of human immunodeficiency virus-1, suggesting that this less-explored chemical space has great potential for further antiviral drug development.