Enantioselective organocatalyzed one-pot synthesis of N-phenyl thioether-tethered tetrasubstituted dihydropyrrole-3-carbaldehydes†‡

Abstract

An efficient method for the asymmetric one-pot synthesis of N-phenyl thioether-tethered tetrasubstituted chiral 4,5-dihydropyrrole-3-carbaldehydes have been developed using readily available benzothiazolium salts and α,β-unsaturated aldehydes as starting materials in the presence of the chiral organocatalyst (R)-diphenylprolinol trimethylsilyl ether. The protocol afforded various functionally enantioenriched chiral tetrasubstituted 4,5-dihydropyrrole-3-carbaldehydes in high yields, with excellent enantio- and diastereoselectivity (≤90% yield, ≤98% ee, and >20 : 1 d.r.). This asymmetric one-pot reaction starts with the reaction of azomethine ylides with dipolarophiles to yield pyrrolo-thiazine-2-carbaldehydes as intermediates. Subsequently, the electrophile alkyl halide is attacked by the sulfur atom of the intermediate, followed by C–S bond cleavage (ring-opening), which furnishes the desired chiral tetrasubstituted 4,5-dihydropyrroles.