A Bioinspired Synthesis of 1,4-Benzothiazines by Selective Addition of Sulfur Nucleophiles to ortho-Quinones

Herein, we report a bioinspired approach to the synthesis of 1,4-benzothiazines by drawing inspiration from the biosynthesis of pheomelanin pigments (pheomelanogenesis). In this context, general conditions for the regioselective coupling reaction between ortho-quinones and thiols were developed. The mild conditions proved amenable to a wide scope of both thiol and ortho-quinone coupling partners while simultaneously suppressing redox-exchange. The utility of this methodology was demonstrated by a synthesis of 1,4-benzothiazines, following a biomimetic, oxidative cyclization.

Automated summary

Here, a bioinspired approach to the synthesis of 1,4-benzothiazines is reported, drawing inspiration from pheomelanin pigments biosynthesis. General conditions for the regioselective coupling reaction between ortho-quinones and thiols were developed. The mild conditions allowed for a wide range of thiol and ortho-quinone coupling partners with suppression of redox-exchange.