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Synthesis 2006(2): 325-331  
DOI: 10.1055/s-2005-924768
PAPER
© Georg Thieme Verlag Stuttgart · New York

Direct Monoalkylation of Alkyl Phosphinates to Access H-Phosphinic Acid Esters

Isabelle Abrunhosa-Thomas, Patrice Ribière, Alicia C. Adcock, Jean-Luc Montchamp*
Department of Chemistry, Box 298860, Texas Christian University, Fort Worth, TX 76129, USA
Fax: +1(817)2575851; e-Mail: j.montchamp@tcu.edu;
Further Information

Publication History

Received 1 July 2005
Publication Date:
21 December 2005 (online)

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Abstract

Simple alkyl phosphinates prepared by the silicate esterification method can be alkylated under Barbier-like conditions with butyl lithium at -78 °C followed by warming to room temperature. The method is limited to the more reactive electrophile such as allylic bromides and alkyl iodides. With these electrophiles good yields of H-phosphinic acid esters are generally obtained in a straightforward manner.

Key words

phosphorus - H-phosphinic acid - phosphinates - alkylation - hypophosphite

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8

The purification of H-phosphinate esters is often complicated by the very polar nature of these compounds, and their relative ease of hydrolysis. Benzyl alkyl-H-phosphinate esters are more labile than other alkyl esters.

14

We thank Jakob Heid, Klemens Kaupmann, and Wolfgang Froestl (Novartis Pharma) for conducting the GTPgammaS binding assay.