β-Amino functionalization of cinnamic Weinreb amides in ionic liquid.

Yi-Ning Wang,Gang Qi,Guo-Xiang Sun

doi:10.3762/bjoc.12.231

Abstract

2-Ns-Protected β-amino Weinreb amides were synthesized by aminochlorination of α,β-unsaturated Weinreb amides in an ionic liquid, 1-n-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide ([BMIM][NTf2]). Processed without the use of metal catalysts or the need of an inert gas atmosphere, the presented process can be readily performed as a one-pot synthesis at room temperature. Moreover, the preparation has the distinct advantages of the use of 2-NsNCl2 as an inexpensive and stable nitrogen/halogen source and the ionic liquid as a recyclable reaction media. Nine examples were examined, and modest to good isolated chemical yields (40–83%) were obtained.

Highlights

Unlike N-protected α-amino carbonyl compounds, their analogues, the β-amino carbonyl compounds, have drawn relatively little attention
With the aminochlorination developed in the past few years [31], we found that when the aminochlorination reactions of α,β-unsaturated ketones 3 were carried out in ionic liquid, [BMIM][NTf2] (1-n-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide, Tf = SO2CF3), a series of α-chloro-βamino ketone derivatives 4 could be obtained with excellent regioselectivities (Scheme 2) [32]
When we switched the ionic liquid to [BMIM][NTf2], it was found that the starting material, N-methoxy-N-methylcinnamoylamide (5a), was consumed completely after 24 h without utilizing any metal catalysts

Summary

Introduction

Unlike N-protected α-amino carbonyl compounds, their analogues, the β-amino carbonyl compounds, have drawn relatively little attention. Great progress has already been achieved, there were still some limitations in the existing syntheses of β-amino Weinreb amides, such as the difficult syntheses of starting materials or the harsh reaction conditions required for the removal of the N-protecting groups.

Results

Conclusion