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

An enantioselective C-P bond formation has been developed through a C(sp(3))-H activation in an oxidation step followed by an organocatalyzed hydrophosphonylation protocol. The asymmetric organocatalytic Pudovik reaction has been achieved following a one-pot strategy, starting from different benzylic and allylic alcohols and dibenzyl phosphite, using MnO2 as the oxidant and a chiral squaramide as organocatalyst. The scope of the reaction provides enantiomerically enriched a-hydroxy phosphonates with yields from 40% to >95% and enantioselectivities from 64% to >99%. Furthermore, the use of this methodology has been demonstrated to form a tetrasubstituted carbon stereocenter, generating an acetophenone derivative in situ, using diphenyl phosphite. Therefore, this approach represents an asymmetric strategy for constructing chiral C-P bonds, which are of interest to the pharmaceutical industry.

Automated summary

An enantioselective C-P bond formation has been developed by activating C(sp(3))-H in an oxidation step, followed by an organocatalytic hydrophosphonylation protocol. The Pudovik reaction achieved asymmetric organocatalysis using a one-pot strategy with different alcohols and phosphite, MnO2 as the oxidant, and a chiral squaramide as the organocatalyst. The reaction scope produced enantiomerically enriched a-hydroxy phosphonates with yields ranging from 40% to >95% and enantioselectivities from 64% to >99%. Furthermore, this methodology has demonstrated the formation of a tetrasubstituted carbon stereocenter in situ, using diphenyl phosphite, to generate an acetophenone derivative. Therefore, this approach represents an asymmetric strategy for constructing chiral C-P bonds, which is significant for the pharmaceutical industry.