α,β-Aziridinylphosphonates by lithium amide-induced phosphonyl migration from nitrogen to carbon in terminal aziridines

David M Hodgson,Zhaoqing Xu

doi:10.3762/bjoc.6.110

Abstract

N-Phosphonate terminal aziridines undergo lithium 2,2,6,6-tetramethylpiperidide-induced N- to C-[1,2]-anionic phosphonyl group migration under experimentally straightforward conditions, to provide a stereocontrolled access to synthetically valuable trans-α,β-aziridinylphosphonates. The utility of this chemistry has been demonstrated in the asymmetric synthesis of a β-aminophosphonate.

Highlights

The synthesis of aminophosphonic acids and their derivatives has attracted considerable attention, since the presence of such functionality, typically as amino acid surrogates, leads to interesting bioactivity in, for example, antibacterial agents, enzyme inhibitors and herbicides [1,2,3]. α,β-Aziridinylphosphonates 3, while possessing biological activity themselves, can be converted into aminophosphonic acids using various ringopening processes [4,5,6]
As to examine the migration chemistry outlined in Scheme 1, access to N-phosphonate terminal aziridines 1 was required [25]
With regard to previous anion-induced N- to C-1,2-shifts in aziridines, in one isolated example, the N-Boc-aziridine of styrene was treated with s-BuLi in THF at –98 °C to give a phenyl-stabilised α-lithiated aziridine, which underwent migration to give 2-phenyl-2-Boc-aziridine (90%) [23]

Summary

Introduction

The synthesis of aminophosphonic acids and their derivatives has attracted considerable attention, since the presence of such functionality, typically as amino acid surrogates, leads to interesting bioactivity in, for example, antibacterial agents, enzyme inhibitors and herbicides [1,2,3]. α,β-Aziridinylphosphonates 3, while possessing biological activity themselves, can be converted into aminophosphonic acids using various ringopening processes [4,5,6]. On the generation and subsequent chemistry of α-lithiated terminal aziridines [14], we considered whether α,βaziridinylphosphonates 3 could be accessed by α-lithiation of N-phosphonate terminal aziridines 1, followed by N- to C-[1,2]anionic phosphonyl group migration in lithiated intermediate 2 (Scheme 1).

Results

Conclusion