First Organocatalytic Asymmetric Biginelli Reaction

X.-H. Chen; X.-Y. Xu; H. Liu; L.-F. Cun; L.-Z. Gong

doi:10.1055/s-2006-955665

Synfacts, Table of Contents

Synfacts 2007(1): 0093-0093
DOI: 10.1055/s-2006-955665

Organo- and Biocatalysis

First Organocatalytic Asymmetric Biginelli Reaction

Contributor(s):Benjamin List, Corinna Reisinger

X.-H. Chen, X.-Y. Xu, H. Liu, L.-F. Cun, L.-Z. Gong*
University of Science and Technology of China, Hefei, Chengdu Institute of Organic Chemistry and , Graduate School of the Chinese Academy of Sciences, Beijing, P. R. of China
Highly Enantioselective Organocatalytic Biginelli Reaction
J. Am. Chem. Soc. 2006, 128: 14802-14803

Abstract

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Key words

Biginelli reaction - multicomponent reaction - phosphoric acid - dihydropyrimidones

Significance

The first highly enantioselective organocatalytic Biginelli reaction is described. Starting from an aldehyde (1), thiourea, and various acetoacetates (2), this acid-catalyzed multicomponent reaction furnishes thio-analogues of diversely substituted 3,4-dihydropyrimidin-2-(1H)-ones (DHPMs) (3), in moderate to good yields and high enantioselectivities. As chiral Brønsted acid organocatalyst the authors employed a binol-derived phosphoric acid. Moreover, three examples of the use of urea instead of thiourea are shown to obtain original DHPMs rather than the thio-analogues. Furthermore, an application in the synthesis of the drug monastrol is reported.

Comment

Multicomponent reactions are of great interest in organic chemistry, since they allow for the rapid and facile access to complex target structures in one step. Moreover, they display an entry to diversity-orientated synthesis, often used in the discovery of new lead compounds in pharmaceutical industry. The heterocyclic Biginelli products are of particular interest since a wide range of dihydropyrimidones exhibits distinct pharmacological properties. To date, only one asymmetric Biginelli reaction with a chiral ytterbium catalyst is known (C. Zhu and co-workers J. Am. Chem. Soc. 2005, 127, 16386-16387).

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