A Method for the Synthesis of Acyclic Haloamines with Ring Opening of Cyclic Amines

The Sarpong group have reported a method to cleave C(sp³)-C(sp³) bonds within unstrained cyclic amines to provide acyclic haloamine products which have multitudes of synthetic utility. In the presence of a cationic halogen source (NBS or NCS), peroxodisulfate, and silver ions, these engage in a SET and HAT redox cycle which readily and mildly oxidizes cyclic Piv-protected amines to iminium ions (1). Hydrolysis and further oxidation provides an amino acid intermediate (2) which is further decarboxylated in the presence of halogen cation sources to afford haloamine products. Varying cyclic amine ring sizes are well tolerated, including bicyclic quinolizidines and prolines. The resulting haloamine products have enormous synthetic potential and can be used in stepwise ring contraction, late-stage total synthesis, peptide synthesis and modification, and are generally anticipated to see wide use within the pharmaceutical, synthetic, and medicinal chemistry fields in industry and academia.