Diastereoselective Palladaelectro-Catalyzed Construction of Bromomethyl Morpholines as Key Step To Access Morpholino Homonucleosides

Org Lett. 2024 Aug 2;26(30):6330-6334. doi: 10.1021/acs.orglett.4c01790. Epub 2024 Jul 22.

Abstract

A synthetic protocol for the preparation of a new class of morpholino homonucleosides in enantiopure form starting from readily available 1,2-aminoalcohols or glycidol has been developed. Key intermediates of the synthetic sequence are 2-bromomethyl morpholines, diastereoselectively achieved from the corresponding alkenols by palladaelectro-catalyzed alkoxybromination of unactivated alkenes. The so obtained bromo derivatives are in turn susceptible to functionalization with nucleic bases for easy access to morpholino homonucleosides.