Morita-Baylis-Hillman reaction of acrylamide with isatin derivatives.

Radhey Mohan Singh,Kishor Chandra Bharadwaj,Dharmendra Kumar Tiwari

doi:10.3762/bjoc.10.315

Abstract

The Morita–Baylis–Hillman reaction of acrylamide, as an activated alkene, has seen little development due to its low reactivity. We have developed the reaction using isatin derivatives with acrylamide, DABCO as a promoter and phenol as an additive in acetonitrile. The corresponding aza version with acrylate and acrylonitrile has also been developed resulting in high product yields.

Highlights

The Morita–Baylis–Hillman (MBH) reaction is an important carbon–carbon bond-forming reaction [1,2,3]
N-phenylacrylamide (1a) was selected as a substrate for the development of the MBH reaction. This approach, together with the activation of acrylamide, was implemented in an attempt to directly vary the electronic properties of the acryl system and to expand the substrate scope
Using two equivalents of acrylamide, DABCO and phenol each at rt was identified as the best condition (Table 1, entry 4)

Summary

Introduction

The Morita–Baylis–Hillman (MBH) reaction is an important carbon–carbon bond-forming reaction [1,2,3]. The reaction between 1a and N-methylisatin (2a) was carried out in the presence of DABCO using acetonitrile as the solvent (Table 1, entry 1). Increasing the reaction time to 5 days resulted in 56% yield (Table 1, entry 2). An increase in the loading of acrylamide (2 equiv, in order to generate more enolate) was helpful and resulted in 71% yield (Table 1, entry 3).

Results

Conclusion