Synthesis of Adamantyl H-Phosphinate Esters

Ricke, Chloe

Publication

Synthesis of Adamantyl H-Phosphinate Esters

Ricke, Chloe

Date

2022

Additional date(s)

5/19/2022

Abstract

Adamantyl H-phosphinate esters were first introduced by Yiotakis et al. as a protecting group in the synthesis of phosphinopeptides. Gatineau et al. later found adamantyl H-phosphinate esters to be useful in the synthesis of P-stereogenic compounds. Phosphorus compounds have a broad range of applications including pharmaceuticals, agricultural products, and flame retardants, making them an area of interest in synthetic chemistry. However, methods for their preparation that achieve high enantioselectivity are limited. Gatineau et al. discovered that adamantyl H-phosphinate esters serve as precursors that facilitate this preparation, which they attributed to the ability of the esters to resist racemization when displaced with organometallics. However, their methods were limited by the necessity of chlorophosphine starting materials. In this project, we aimed at developing novel synthetic methods for the preparation of adamantyl H-phosphinate esters which are not limited in terms of available reagents and are less expensive than current known methods. EDC, PivCl, and T3P were utilized in the esterification reactions. Methods were developed to prepare these esters in good yield on a multigram scale without the need for chromatography. An alternative method to the esterification of H-phosphinic acids was also employed that involved the preparation of adamantyl hypophosphite and its conversion into a variety of H-phosphinate esters. However, adamantyl hypophosphite was shown to have limited reactivity.