Organocatalytic asymmetric Henry reaction of 1H-pyrrole-2,3-diones with bifunctional amine-thiourea catalysts bearing multiple hydrogen-bond donors.

Ming-Liang Zhang,Zhen-Hua Wang,Xiao-Ying Xu,Xiao-Mei Zhang,Wei-Cheng Yuan,Yuan Luo,Deng-Feng Yue

doi:10.3762/bjoc.12.31

Ming-Liang Zhang, Zhen-Hua Wang + Show 5 more

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https://doi.org/10.3762/bjoc.12.31

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Abstract

For the first time, a catalytic asymmetric Henry reaction of 1H-pyrrole-2,3-diones was achieved with a chiral bifunctional amine-thiourea as a catalyst possessing multiple hydrogen-bond donors. With this developed method, a range of 3-hydroxy-3-nitromethyl-1H-pyrrol-2(3H)-ones bearing quaternary stereocenters were obtained in acceptable yield (up to 75%) and enantioselectivity (up to 73% ee).

Highlights

Asymmetric organocatalysis has been demonstrated to be an effective and versatile strategy in facilitating a variety of organic transformations over the past decade, and numerous catalytic asymmetric reactions have been developed with various activation modes [1,2,3,4,5,6]
As part of our research program aimed at establishing new methods for the construction of quaternary stereocenters [35,36,37], we envisioned that the Henry reaction of nitroalkanes with 1H-pyrrole-2,3-diones should take place with a chiral bifunctional amine-thiourea catalyst, leading to
The reactions in ethers gave improved yield with slightly increased enantioselectivity (Table 1, entries 8–10). Strong polar solvents such as acetonitrile and ethyl acetate proved inferior to this Henry reaction (Table 1, entries 11 and 12)

Summary

Introduction

Asymmetric organocatalysis has been demonstrated to be an effective and versatile strategy in facilitating a variety of organic transformations over the past decade, and numerous catalytic asymmetric reactions have been developed with various activation modes [1,2,3,4,5,6]. As part of our research program aimed at establishing new methods for the construction of quaternary stereocenters [35,36,37], we envisioned that the Henry reaction of nitroalkanes with 1H-pyrrole-2,3-diones should take place with a chiral bifunctional amine-thiourea catalyst, leading to The reaction proceeded and gave the desired product 4a in 18% yield and 28% ee with cinchonidine and L-valine-based catalyst 3a (Table 1, entry 1). The reaction was attempted with catalyst 3c derived from L-phenylalanine and catalyst 3d derived from L-phenylglycine, and improvements in enantioselectivity were observed (Table 1, entries 3 and 4).

Results

Conclusion