Selective Benzylic and Allylic Alkylation of Protic Nucleophiles with Sulfonamides through Double Lewis Acid Catalyzed Cleavage of sp3 Carbon–Nitrogen Bonds

Abstract

The acid-catalyzed benzylic and allylic alkylation of protic nucleophiles is fundamentally important for the formation of carbon-carbon and carbon-heteroatom bonds, and it is a formidable challenge for benzylic and allylic amine derivatives to be used as the alkylating agents. Herein we report a highly efficient benzylic and allylic alkylation of protic carbon and sulfur nucleophiles with sulfonamides through double Lewis acid catalyzed cleavage of sp(3) carbon-nitrogen bonds at room temperature. In the presence of a catalytic amount of inexpensive ZnCl(2)-TMSCl (TMSCl: chlorotrimethylsilane), 1,3-diketones, beta-keto esters, beta-keto amides, malononitrile, aromatic compounds, thiols, and thioacetic acid can couple with a broad range of tosyl-activated benzylic and allylic amines to give diversely functionalized products in good to excellent yields and with high regioselectivity. Furthermore, the cross-coupling reaction of 1,3-dicarbonyl compounds with benzylic propargylic amine derivatives has been successfully applied to the one-step synthesis of polysubstituted furans and benzofurans.