Cycloaddition/ring-opening cascade reaction of alkylidene azlactones for the synthesis of α,α-disubstituted α-amino acid esters

Abstract

We report a metal-free, solvent-controlled, diastereoselective one-pot cascade reaction between alkylidene azlactones and N-phenacylbenzothiazolium salts, enabling efficient access to pyrrolo[2,1-b]benzothiazole-based α,α-disubstituted α-amino acid esters under ambient conditions. The transformation proceeds via a [3 + 2] annulation followed by a methanol-triggered azlactone ring-opening, forging two C–C bonds and generating four contiguous stereogenic centers, including a quaternary carbon, in a single operation with complete diastereocontrol. The protocol offers high yields, broad substrate scope, and mechanistic support is obtained from control and spectroscopic studies.