Chinchona alkaloid

Chinchona alkaloids, such as quinine, are readily available quinuclidine chiral bases which have been used extensively in catalytic Michael additions239 243. Methy 1-2,3-dihydro-1-oxo-l/f-in-dene-2-carboxylate (1) is most frequently used as the Michael donor in these studies. Enantiose-lectivities as high as 76% are reached in the additions to 3-buten-2-one. Modest enantioselec-tivities (< 67%) were also obtained with ethyl 2-oxo-l-cyclohexanecarboxylate and methyl l,3-dihydto-3-oxo-l-isobcnzol urancarboxylate244 245. 

The group of Terashima [35] developed an asymmetric domino Michael/aldol process using the chinchona alkaloid (-)-cinchonidine (2-103), to prepare an intermediate for the synthesis of the natural product (-)-huperzine A (2-102) [36] (Scheme 2.22). 

The importance of chiral thiols and thioether linkages in biological systems has prompted intense investigation of the use of chiral amines [see e.g. 5-11] and ammonium salts [see e.g. 12] as agents for asymmetric induction in the Michael-type addition reaction. Considerable success has been achieved using chinchona alkaloids and their A-alkyl derivatives (see Chapter 12). 

Thiols may be enantioselectiveiy added in a conjugate fashion to a,p-unsaturated carbonyl compounds in the presence of chiral hydroxyamine catalysts e.g. chinchona alkaloids).242,244 249 252-261-269 In some cases ee of up to >80% were achieved e.g. Scheme 77).242-261-262 This methodology was utilized for the kinetic resolution of compound rat-86 Scheme 34) in a multigram scale.94 Related enantioselective 1,4-additions of thioacetates270-271 and selenophenols272 to enones are also known. Epoxidations, based on the asymmetric nucleophilic addition of peroxide anions to enones, are discussed separately.273... 

Two groups have developed effective immobilized Chinchona alkaloid phase transfer catalysts, with a connection to a polymer support either through the N-benzyl group or an O-benzyl group [13-15]. 

Aldol reactions using a quaternary chinchona alkaloid-based ammonium salt as orga-nocatalyst Several quaternary ammonium salts derived from cinchona alkaloids have proven to be excellent organocatalysts for asymmetric nucleophilic substitutions, Michael reactions and other syntheses. As described in more detail in, e.g., Chapters 3 and 4, those salts act as chiral phase-transfer catalysts. It is, therefore, not surprising that catalysts of type 31 have been also applied in the asymmetric aldol reaction [65, 66], The aldol reactions were performed with the aromatic enolate 30a and benzaldehyde in the presence of ammonium fluoride salts derived from cinchonidine and cinchonine, respectively, as a phase-transfer catalyst (10 mol%). For example, in the presence of the cinchonine-derived catalyst 31 the desired product (S)-32a was formed in 65% yield (Scheme 6.16). The enantioselectivity, however, was low (39% ee) [65],... 

R3N could be an expensive chiral amine catalyst such as a chinchona alkaloid, whereas the proton sponge is used stoichiometrically. For achiral reactions, NEt3 can serve both functions. The subsequent reaction follows the pathway known from the reverse mode reactions, with the catalyst recovered unchanged ... 

R3N could be an expensive chiral amine catalyst such as a chinchona alkaloid, whereas the proton sponge is used... 

Figure 5.8 Stuctures of Chinchona alkaloid derived ligands...

Conversion of chinchona alkaloids of the quinoline series to those of the indole series Ochiai ei a .. CA, 59, 14040h (1963). 

The Sharpless catalytic asymmetric dihydroxylation of olefins, using catalytic amounts of osmium tetroxide in the presence of chinchona alkaloid derivatives, allowed access to a variety of enantiomerically pure 1,2-diols Scheme 3.6.1). 

Matsui, J. Nicholls, I.A. Takeuchi, T. Molecular recognition in chinchona alkaloid molecular imprinted polymer rods. Anal. Chim. Acta 1998, 365, 89-93. 

The most important Chinchona alkaloids are quinoline derivatives. The quinoline nucleus of these compounds is linked at position 4 via a secondary alcoholic group to the so-called quinuclidine nucleus, a system of two piperidine rings with a common nitrogen atom and three common C-atoms. A number of differently substituted and isomeric alkaloids exist. Of special importance are the alkaloids quinine and quinidine. 

Li, H. Wang, Y. Tang, L. Deng, L. Highly Enantioselective Addition of Malonate and 3-Ketoester to Nitroalkenes Asymmetric C-C Bond Formation with New Bifunctional Organic Catalysts Based on Chinchona Alkaloids. /. Am. Chem. Soc. 2004,126, 9906-9907. 

A recent chemical scheme uses a chinchona alkaloid dmvative as the starting matnial to produce 2a,3a,22R,23R qnbrassinolide, as a major product (17). Although 24-qnbrassinoli is only about 10% as active in certain bioassays, including radish and tomato, its activity in fidd trials is iq>proximatdy equal to brassinolide and it is an attractive candidate for industrial devdqpment because of the rdative ease with which it can be synthesized. 

Zhao M-X, Zhang Z-W, Chen M-X, Tang W-H, Shi M. Chinchona alkaloid catalyzed enantioselective chlorination of 3-aryloxindoles. Eur. J. Org. Chem. 2011 (16) 3001 3008. 

Strecker reactions of ethyl cyanoformate with cyclic (Z)-aldimines (indoles and thi-azines) catalysed by chinchona alkaloid derivatives,and with various aromatic and aliphatic A(-benzhydrylimines catalysed by a chiral polyamide (12), " proceed with excellent ee values. 

The NH group of a series of substituted isatins reacts with a wide range of 2-aryl Morita-Bayless-Hillman carbonates in the presence of a chinchona alkaloid... 

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