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Journal ArticleDOI

Highly Enantioselective Construction of a Quaternary Carbon Center of Dihydroquinazoline by Asymmetric Mannich Reaction and Chiral Recognition

09 Jun 2008-Advanced Synthesis & Catalysis (John Wiley & Sons, Ltd)-Vol. 350, Iss: 9, pp 1360-1366
TL;DR: In this paper, a chiral trifluoromethyl quaternary carbon center of dihydroquinazoline was constructed by an asymmetric Mannich reaction and chiral recognition.
Abstract: The highly enantioselective construction of a quaternary carbon center of dihydroquinazoline by an asymmetric Mannich reaction and chiral recognition are described The key transformation was to establish the chiral trifluoromethyl quaternary carbon center by a diamine-Bronsted acid-catalyzed enantioselective and regioselective Mannich reaction of a methyl ketone and 4-trifluoromethyldihydroquinazoline An unusual phenomenon of self-discrimination of enantiomers in hydrogen-bonded dimers was observed A valuable intermediate was transformed into the enantiopure HIV reverse transcriptase inhibitor DPC 083 (>999 ee) simply by reduction of the carbonyl group and elimination of the hydroxy group in hexamethylphosphoric tramide (HMPA)
Citations
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Journal ArticleDOI
TL;DR: This poster presents a probabilistic analysis of the response of Na6(CO3)(SO4)(SO3) to Na2SO4 using a high-resolution X-ray diffraction analysis for the stationary phase.
Abstract: Department of Chemistry, Tianjin University, Tianjin 300072, China; Department of Applied Chemistry, China Agricultural University, Beijing 100193, China; UMR 6014 CNRS, Laboratoire COBRA de l’IRCOF, Université et INSA de Rouen, Rue Tesniere, F-76130 Mont Saint Aignan, France; and Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Science, Shanghai 200032, China

851 citations

Journal ArticleDOI
TL;DR: X-ray crystallographic analysis revealed that the hydrogen bonding between the sulfonimide proton and the 8-quinolyl nitrogen atom plays an important role in exerting the enantioselectivity of the reaction.
Abstract: The organocatalytic enantioselective decarboxylative addition of malonic acid half thioesters to ketimines derived from isatins by using N-heteroarenesulfonyl cinchona alkaloid amides afforded products with high enantioselectivity. The products could be converted into optically active AG-041R. X-ray crystallographic analysis revealed that the hydrogen bonding between the sulfonimide proton and the 8-quinolyl nitrogen atom plays an important role in exerting the enantioselectivity of the reaction.

150 citations

Journal ArticleDOI
TL;DR: A comprehensive overview of the applications of asymmetric organocatalysis in medicinal chemistry can be found in this article, with a focus on the preparation of antiviral, anticancer, neuroprotective, cardiovascular, antibacterial, and antiparasitic agents, as well as several miscellaneous bioactive agents.
Abstract: The efficacy and synthetic versatility of asymmetric organocatalysis have contributed enormously to the field of organic synthesis since the early 2000s. As asymmetric organocatalytic methods mature, they have extended beyond the academia and undergone scale-up for the production of chiral drugs, natural products, and enantiomerically enriched bioactive molecules. This review provides a comprehensive overview of the applications of asymmetric organocatalysis in medicinal chemistry. A general picture of asymmetric organocatalytic strategies in medicinal chemistry is firstly presented, and the specific applications of these strategies in pharmaceutical synthesis are systematically described, with a focus on the preparation of antiviral, anticancer, neuroprotective, cardiovascular, antibacterial, and antiparasitic agents, as well as several miscellaneous bioactive agents. The review concludes with a discussion of the challenges, limitations and future prospects for organocatalytic asymmetric synthesis of medicinally valuable compounds.

144 citations

Journal ArticleDOI
Hai-Na Yuan1, Shuai Wang1, Jing Nie1, Wei Meng1, Qingwei Yao, Jun-An Ma1 
TL;DR: Efforts are reported in developing a hydrogenbond-directed enantioselective decarboxylative Mannich reaction of b-ketoacids by employing cyclic N-acyl ketimines as the electrophilic acceptor and this new reaction was cooperatively promoted by saccharide-based bifunctional organocatalysts.
Abstract: This is the first hydrogen-bond-directed enantioselective decarboxylative Mannich reaction of β-ketoacids with ketimines affording quinazolinone derivatives with quaternary stereocenters in high yields and with excellent enantioselectivities using saccharide-based amino-thiourea organocatalysts.

136 citations

References
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Journal ArticleDOI
TL;DR: The contributions of this laboratory to converting enzymatic enamines, and in some cases imines, into a versatile catalytic asymmetric strategy powered by small organic molecules are summarized.
Abstract: Enamines and imines have long been recognized as key intermediates in enzyme catalysis, particularly within a class of enzymes organic chemists would very much like to emulate, the aldolases. Here we summarize the contributions of this laboratory to converting enzymatic enamines, and in some cases imines, into a versatile catalytic asymmetric strategy powered by small organic molecules.

1,192 citations

Journal ArticleDOI
TL;DR: The direct catalytic asymmetric addition of unmodified carbonyl compounds to preformed or in situ-generated imines has emerged as a promising new route to optically enriched alpha- and beta-amino acid derivatives, beta-lactams, and 1,2- and gamma-aminos alcohols.
Abstract: The direct catalytic asymmetric addition of unmodified carbonyl compounds to preformed or in situ-generated imines has emerged as a promising new route to optically enriched alpha- and beta-amino acid derivatives, beta-lactams, and 1,2- and gamma-amino alcohols. The direct catalytic asymmetric Mannich reactions are mediated by small organometallic and organic amine catalysts that can achieve levels of selectivity similar to those possible with natural enzymes. The different small-molecule catalysts described here are complementary in their applications. They also complement each other in syn or anti selectivity of the direct asymmetric Mannich reaction. In this Account, we highlight the recent developments in and contributions to this research.

641 citations

Journal ArticleDOI
TL;DR: Proline-catalyzed direct asymmetric three-component Mannich reactions of ketones, aldehydes, and amines are developed and application to the highly enantioselective synthesis of 1,2-amino alcohols is presented.
Abstract: We have developed proline-catalyzed direct asymmetric three-component Mannich reactions of ketones, aldehydes, and amines. Several of the studied reactions provide β-amino carbonyl compounds (Mannich products) in excellent enantio-, diastereo-, regio-, and chemoselectivities. The scope of each of the three components and the influence of the catalyst structure on the reaction are described. Reaction conditions have been optimized, and the mechanism and source of asymmetric induction are discussed. We further present application of our reaction to the highly enantioselective synthesis of 1,2-amino alcohols.

555 citations

Journal ArticleDOI
TL;DR: This tutorial review provides an overview of the recent history of the asymmetric organocatalysed Mannich reaction, including scope and limitations, and application of different catalyst systems.
Abstract: The asymmetric Mannich reaction ranks among the most potent enantioselective and diastereoselective C–C-bond forming reactions. In recent years, organocatalysed versions of asymmetric Mannich processes have been increasingly reported and used in a rapidly growing number of applications. This tutorial review provides an overview of the recent history of the asymmetric organocatalysed Mannich reaction, including scope and limitations, and application of different catalyst systems.

484 citations

Journal ArticleDOI
TL;DR: In this paper, the authors present the methodology and synthetic advantages achieved so far in the asymmetric Mannich reaction, and present a Microreview of the recent contributions to this process.

385 citations