Synthesis of N-Acylsulfenamides from (Hetero)Aryl Iodides and Boronic Acids by One-Pot Sulfur-Arylation and Dealkylation

Abstract

A general one-pot approach to diverse N-acylsulfenamides from a common S-phenethylsulfenamide starting material is reported. This approach was demonstrated by C−S bond formation utilizing commercially abundant (hetero)aryl iodides and boronic acids to provide sulfilimine intermediates that undergo thermal elimination of styrene. In contrast, all prior approaches to N-acylsulfenamides rely on thiol inputs to introduce sulfenamide S-substituents. A broad scope of reaction inputs was demonstrated including for approved drugs and drug precursors with dense display of functionality. Several different types of sulfur functionalization were performed on a sulfenamide derived from a complex precursor of the blockbuster anticoagulant drug apixaban, highlighting the utility of this approach for the introduction of high oxidation state sulfur groups in complex bioactive compounds. Mechanistic studies established that the key styrene elimination step proceeds by a concerted elimination that does not require reagents or catalysts, and therefore, this one-pot approach should be applicable to the synthesis of N-acylsulfenamides utilizing diverse electrophiles and reaction conditions for C−S bond formation.