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Synthesis 2011(3): 437-442  
DOI: 10.1055/s-0030-1258387
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Application of Bis(trimethylsilyl) Phosphonite in the Efficient Preparation of New Heterocyclic α-Aminomethyl-H-phosphinic Acids

Tomasz K. Olszewski*, Bogdan Boduszek
Department of Chemistry, Wroclaw University of Technology, Wybrzeze St. Wyspianskiego 27, 50-370 Wroclaw, Poland
Fax: +48(71)3284064; e-Mail: tomasz.olszewski@pwr.wroc.pl;
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Publication History

Received 21 September 2010
Publication Date:
28 December 2010 (online)

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Abstract

A simple, reproducible, and efficient preparation of new heterocyclic α-aminomethyl-H-phosphinic acids is reported. The synthetic protocol is based on the application of bis(trimethylsilyl) phosphonite, as an efficient phosphorous nucleophile, in the reaction with the corresponding heterocyclic imines. Subsequent methanolysis of the addition intermediates leads to the expected heterocyclic α-aminomethyl-H-phosphinic acids in fair to good yields. Additionally, acidic hydrolysis of benzhydrylamino derivatives allows the efficient preparation of free α-aminomethyl-H-phosphinic acids in good yields and high purity after simple crystallization.

Key words

heterocycles - phosphorus - aldehydes - imines - hydrolysis

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15

Other protecting groups such as trityl(triphenylmethyl) and benzyl were also used. In the case of trityl group the yields of N-protected H-phosphinic acids were low (in the range of 40%). Furthermore the not easy availability of tritylamine was an additional drawback. In the case of the benzyl group we were unable to remove this protecting group. All attempts to hydrogenolyze N-benzyl-H-phosphinic acids failed probably due to catalyst poisoning by the H-phos-phinic acid.

16

Crystalline hydrochlorides of 5 could be obtained at this stage, but in our hands they were always very hygroscopic.