Efficacy of Selenourea Organocatalysts in Asymmetric Michael Reactions under Standard and Solvent-Free Conditions.

Mariola Zielińska-Błajet,Żaneta A Mała,Rafał Kowalczyk

doi:10.3390/molecules26237303

Abstract

By varying the steric and electronic surroundings of the hydrogen-bonding motif, the novel chiral Cinchona-alkaloid based selenoureas were developed. Acting as bifunctional catalysts, they were applied in the Michael reactions of dithiomalonate and nitrostyrene providing chiral adducts with up to 96% ee. The asymmetric Michael–-hemiacetalization reaction of benzylidene pyruvate and dimedone, performed with the assistance of 5 mol% of selenoureas, furnished the product with up to 93% ee and excellent yields. The effectiveness of the new hydrogen-bond donors was also proved in solvent-free reactions under ball mill conditions, supporting the sustainability of the devised catalytic protocol.

Highlights

The asymmetric Michael addition reaction is widely recognized as one of the most important synthetic methods for the formation of C−C bonds [1]
An inexpensive and readily available Cinchona alkaloid has been used as a chiral scaffold for the synthesis of thiourea catalysts and proved effective in several asymmetric reactions with excellent enantioselectivity [4,5]
Alkyl and aryl isoselenocyanates 3a–e were synthesized in a three‐step protocol involved the N-formylation of the commercially available amines with formic acid in (Scheme 1) that involved the N‐formylation of the commercially available amines with toluene or in methyl formate, followed by the conversion formic acid in toluene or in methyl formate, followed by of the formamides 2a–e into isocyanides upon dehydration with POCl3 in the presence of the conversion of the formamides 2a–e into isocyanides upon dehydration with POCl3 in

Summary

Introduction

The asymmetric Michael addition reaction is widely recognized as one of the most important synthetic methods for the formation of C−C bonds [1]. After the pioneering work of Jacobsen and Takemoto [2,3], significant progress has been made in the development and application of bifunctional chiral thiourea catalysts in catalytic asymmetric reactions. An inexpensive and readily available Cinchona alkaloid has been used as a chiral scaffold for the synthesis of thiourea catalysts and proved effective in several asymmetric reactions with excellent enantioselectivity [4,5]. Intrigued by how the change of hydrogen-bonding affinity of selenoureas in a chiral framework would impact the chirality transfer in comparison to well-developed thioureas

Methods

Discussion

Conclusion