Synthesis of aminate amides by sulfonium rearrangement

This project focuses on the development of a novel synthetic methodology for the enantioselective preparation of a- and ß-amino acid derivatives, employing readily or commercially available enantioenriched sulfinamides as the source of both nitrogen and chiral information. This divergent, direct functionalization of amides leads to the formation of either CN or CC bonds, yielding valuable synthetic building blocks amenable to downstream transformation into potentially bioactive substances. The use of charge-accelerated sulfonium rearrangements has emerged as a valuable strategy for the preparation of tertiary or quaternary stereocenters. On the other hand, enantioenriched sulfinamides, widely referred to as Ellmans auxiliaries, are heavily used in the synthesis of agrochemicals and natural products, as well as for the preparation of chemical tools for biological investigations. We propose that the reaction of either sulfinamides or sulfinimines with electrophilically generated keteniminium ions can lead to the formation of intermediates ideally poised for charge-accelerated sulfonium rearrangements. Leveraging these intermediates into subsequent stereospecific [2,3]- or [3,3]-sulfonium rearrangements enables CN or CC bond formation to yield a- or ß-amino acid derivatives, in enantioenriched form. Notably, our preliminary investigations demonstrate the feasibility of both transformations.

This research focuses on the development of a novel synthetic methodology for the enantioselective preparation of and -amino acid derivatives, employing readily or commercially available enantioenriched sulfinamides as the source of both nitrogen and chiral information. This divergent, direct functionalization of amides leads to the formation of either C-N or C-C bonds, yielding valuable synthetic building blocks amenable to downstream transformation into potentially bioactive substances.