Issue 18, 2012

Highly efficient asymmetric anti-Mannich reactions of carbonyl compounds with N-carbamoyl imines catalyzed by amino-thiourea organocatalysts§

Abstract

A series of pyrrolidine-based organocatalysts which bear three synergistic features, i.e. secondary amino group, various H-bond donor groups at the 4-position and a stereocontrol silyl ether group at the α-position of the pyrrolidine nitrogen atom, were developed. They were screened in anti-Mannich reactions of carbonyl compounds with preformed or in situ generated N-protected α-imino ethylglyoxylate and aldehydes with preformed or in situ generated N-carbamoyl imines. The influence of H-bond donor ability at the 4-position was also investigated. Among all the catalysts, 2a was identified as a general efficient organocatalyst suitable for various types of anti-Mannich reactions and broad substrate scope. Excellent results (up to 98% yield, >99% ee and >99 : 1 dr) were achieved with 5 mol% catalyst load. Sulfones with ortho substituents or very strong withdrawing groups on the aromatic ring, which have been regarded as challenging substrates in the direct anti-Mannich reactions of aldehydes with in situ generated N-carbamoyl imines, also worked well. The optimization of our catalytic system also offered alternative and easily operational protocols to access anti-Mannich products with orthogonal N-Boc or N-Cbz protecting groups.

Graphical abstract: Highly efficient asymmetric anti-Mannich reactions of carbonyl compounds with N-carbamoyl imines catalyzed by amino-thiourea organocatalysts

Supplementary files

Article information

Article type
Paper
Submitted
09 Jan 2012
Accepted
29 Feb 2012
First published
02 Mar 2012

Org. Biomol. Chem., 2012,10, 3730-3738

Highly efficient asymmetric anti-Mannich reactions of carbonyl compounds with N-carbamoyl imines catalyzed by amino-thiourea organocatalysts

J. Gao, Y. Chuan, J. Li, F. Xie and Y. Peng, Org. Biomol. Chem., 2012, 10, 3730 DOI: 10.1039/C2OB00049K

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