Reversal Diastereoselectivity in the Benzylation of Phosphonopropanoamides

Abstract

A convenient and efficient preparation of phosphonopropanoamides bearing (S)-1-(1′-naphthyl)ethylamine, (S)-3,3-dimethyl-2-butylamine, and (S)-2-amine-3-methylbutane in good yield has been achieved. The stereochemical outcome of the asymmetric benzylation reaction of their enolates changes dramatically with the LDA equivalents used. The enolization of the phosphopropanoamides with LDA (2 equiv.) followed by the reaction with benzyl bromide gives rise to the (R,S) quaternary phosphonoamides, whereas the (S,S) diastereoisomer can be obtained by enolization with LDA (≥2.5 equiv.) followed by the addition of benzyl bromide. This method provides access to both diastereoisomers changing only the base equivalents.

Keywords:

• Aminophosphonates
• diastereoselective benzylation
• phosphonoamides
• quaternary stereocenter
• reversal diastereoselectivity

Acknowledgments

This work was carried out with the financial support of CONACYT-MEXICO (Project 62271), and (in part) by CONACYT-MEXICO-INDIA (Bilateral Project J110.501/2006).