Coupling of 1-Chloro-N,N-diisopropylphosphanamine-Based Reagents with Alcohols and Thiosulfonates: A Precise Construction of O-P(O)-S Bonds

Herein, we present the first mild, one-step direct synthesis of mixed phosphorothioates through selective generation of O-P(O)-S bonds at rt under additive-free condition. Further, reactions of different model natural products with 1,1-dichloro-N,N-diisopropylphosphanamine helped to present an alternative dimerization strategy. The synthetic utility of the methodology was extended for the synthesis of mixed phosphoroselenoates as well. The potential of the reaction was further demonstrated for the synthesis of mixed phosphorothioate bearing two different alcohols.

Automated summary

In this study, we present the first mild and one-step direct synthesis of mixed phosphorothioates through the selective generation of O-P(O)-S bonds at room temperature without the need for additives. Additionally, we demonstrate an alternative dimerization strategy using reactions between different model natural products and 1,1-dichloro-N,N-diisopropylphosphanamine. The methodology was also successfully extended to the synthesis of mixed phosphoroselenoates and mixed phosphorothioates bearing two different alcohols.