Asymmetric organocatalytic decarboxylative Mannich reaction using β-keto acids: A new protocol for the synthesis of chiral β-amino ketones

Chunhui Jiang,Fangrui Zhong,Yixin Lu

doi:10.3762/bjoc.8.144

Abstract

The first decarboxylative Mannich reaction employing β-keto acids, catalyzed by cinchonine-derived bifunctional thiourea catalyst has been described. The desired β-amino ketones were obtained in excellent yields and with moderate to good enantioselectivities.

Highlights

Chiral β-amino ketones are an important class of building blocks for the synthesis of 1,3-amino alcohols [1,2], 1,3-amino acids [3] and other bioactive nature products [4,5,6]
We examined the model reaction between tosylimine 1a and β-keto acid 2a in the presence of a range of bifunctional catalysts (Table 1)
We examined several other bifunctional catalysts based on amino acids [43,44], including threonine derived Thr-1 [45], and tryptophan based Trp-1 [46], as well as threonine incorporated multifunctional catalyst CD-3

Summary

Introduction

Chiral β-amino ketones are an important class of building blocks for the synthesis of 1,3-amino alcohols [1,2], 1,3-amino acids [3] and other bioactive nature products [4,5,6]. We reported the first decarboxylative Mannich reaction between the β-keto acids and sulfonylimines, affording chiral β-amino ketones in excellent yields and good enantioselectivities. We examined the model reaction between tosylimine 1a and β-keto acid 2a in the presence of a range of bifunctional catalysts (Table 1). Available cinchonidine (CD-1) led to the formation of the product with disappointing enantioselectivity (Table 1, entry 1).

Results

Conclusion