On the synthesis of α-amino sulfoxides

Abstract

A synthetic study on the preparation of N-Boc α-amino sulfoxides has revealed an unexpected instability which is believed to be due to α-elimination of the sulfoxide to give an iminium ion. Full synthetic details are reported on two main synthetic routes: lithiation and sulfinate trapping of N-Boc heterocycles and oxidation of N-Boc α-amino sulfides. Six novel α-amino sulfoxides were successfully prepared and isolated. It is speculated that four other α-amino sulfoxides were synthesised but could not be isolated due to their propensity to α-eliminate the sulfoxide. Ultimately, a stable, cyclic N-Boc α-amino sulfoxide was prepared and this successful synthesis relied on the α-amino sulfoxide being part of a bicyclic [3.1.0] fused ring system that could not undergo α-elimination of the sulfoxide.

Radical C(sp3)–S Coupling for the Synthesis of α-Amino Sulfides

“…Organic sulfur-containing compounds are ubiquitous in natural products and various biological systems . As a subclass of these, α-amino sulfides with important biological activity and medicinal value have long encouraged organic chemists to explore novel methods dedicated to their synthesis. To the best of our knowledge, there have been relatively few previous reports on the synthesis of α-amino sulfides, the key to which is the formation of C–S bonds …”

Photoinduced C(sp3)–H Chalcogenation of Amide Derivatives and Ethers via Ligand-to-Metal Charge-Transfer

“…Traditional synthetic approaches to access these amido- N,S -acetals proceed through either the substitution reaction of halogenated amides at the amino carbon, or through the addition reaction to N -acyl imines by thiol nucleophiles. Unfortunately these prefunctionalized imines and halogenated intermediates are often unstable to moisture, not easily stored for prolonged periods of time, and require sophisticated reaction conditions . Direct C–H thiolation of amides represent a more attractive approach for late-stage diversification and functionalization, and bypasses the need for these unstable intermediates.…”