Enantioselective Chan–Lam S-arylation of sulfenamides

Abstract

Sulfur stereogenic molecules have a significant impact on drug development. Among them, sulfilimines are chiral molecules bearing S(IV) stereocentres, which exhibit great value in chemistry and biology but have so far been synthetically challenging to achieve. Similarly, it has also been a challenge to control the stereochemistry in Chan–Lam coupling, which has been widely used to construct C–N, C–O and C–S bonds by coupling nucleophiles with boronic acids using copper complexes. Here we report a highly chemoselective and enantioselective Chan–Lam S-arylation of sulfenamides with arylboronic acids to deliver an array of thermodynamically disfavoured aryl sulfilimines containing a sulfur stereocentre. A copper catalyst from a 2-pyridyl N-phenyl dihydroimidazole ligand has been designed that enables effective enantiocontrol by means of a well-defined chiral environment and high reactivity that outcompetes the background racemic transformation. A combined experimental and computational study establishes the reaction mechanism and unveils the origin of chemoselectivity and stereoselectivity. Sulfilimines are a class of chiral molecules that bear S(IV) stereocentres, which are of high value in drug discovery but difficult to synthesize. Now the authors report a chemo- and enantioselective Chan–Lam S-arylation of sulfenamides with arylboronic acids that delivers diaryl and alkyl aryl sulfilimines.