Enantioselective C–P Bond Formation through C(sp3)–H Functionalization

03 April 2023, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

An unprecedented enantioselective C–P bond formation has been developed through a C(sp3)–H activation in an oxidation step followed by an organocatalyzed hydrophosphonylation protocol. The asymmetric organocatalytic Pudovik reaction has been successfully achieved following a one-pot strategy, starting from different benzylic alcohols and dibenzylphosphite, using MnO2 as the oxidant and a chiral squaramide as organocatalyst. The scope of the reaction provides enantiomerically enriched α-hydroxy phosphonates in good to excellent yields (up to >95%) and high enantioselectivities (up to >99%). Furthermore, the use of this methodology has been successfully demonstrated to form a quaternary centre, generating an acetophenone derivative in situ, using diphenyl phosphite. Therefore, this approach represents a highly effective strategy for constructing chiral C–P bonds, which are of significant interest to the pharmaceutical industry. This proof of concept represents a significant breakthrough in the field of chemistry.

Keywords

C–H activation • C–P formation • organocatalysis • oxidation • Pudovik • squaramide • one-pot

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