Iminium catalysts activation mode

Following the same iminium ion activation mode but with cinchona primary-tertiary diamine bifunctional catalyst 9, Chen and co-workers [108] described the asymmetric intramolecular aza-Michael addition of enone carbamates (Scheme 11.29). The reactions proceed in high yield and with good to excellent stereocontrol (up to 99% ee). 

Since the early example of a proline-catalyzed asymmetric domino Michael-aldol reaction reported by Bui and Barbas in 2000 [57], a number of these reactions have been successfully developed by several groups. For example, Wang et al. have reported the synthesis of chiral densely functionalized cyclopentenes on the basis of a domino Michael-aldol reaction followed by dehydration between aromatic enals and dimethyl 2-oxoethylmalonate [67]. High yields (63-89%) and enanhose-lectivities (91-97% ee) were obtained by using (S)-diphenylprolinol sUyl ethers as catalysts. On the other hand, the condensation of P-nitroketones 36 onto enals in the presence of 8 was shown by Hong et al. to afford the corresponding domino Michael-aldol products 37 through the iminium-enamine activation mode [68]. 

The majority of transformations reported within the literature using the concept of LUMO energy lowering iminium ion activation have nsed secondary amines as the catalyst. Under the aqueous acidic reaction conditions inherent to this mode of activation it is also possible to nse primary amines as efficient catalysts where the active species is the protonated imine 141 (Fig. 13). Althongh this is a somewhat less explored avenne of research, initial results suggest it will become an equally fruitful area with broad application. 

The direct asymmetric aldol reaction is a powerful tool for C-C bond formation. Enamine-iminium catalysis is the most developed, and it is nicely complimented by other modes of activation that rely on hydrogen bond formation. Mechanistically, all proline-based catalysts activate donors through the formation of an enamine intermediate. Other activation modes rely on enolate formation, ionic interactions, or hydrogen bond formation, though the mechanism is not always known. 

The use of chiral amine catalysts also allows for the combination of alternative activation modes, that is, enamine/ iminium activation in operationally simple one-pot cascade reactions, either with a single catalyst or using multiple catalysts [52]. A broad variety of the organocascade approaches... 

Complementary to the enamine-based reactions, the diarylprolinol silyl ether catalysts can be applied for activation of a,p-unsaturated aldehydes toward conjugate additions through iminium-ion-induced processes. Mechanistically, this conceptually different activation mode draws close parallels to the enamine chemistry (Scheme 2.4) [5]. The secondary aminocatalyst condenses with the enal to form... 

Chiral amine-mediated organocaialytic cascade reactions have become a benchmaik in contemporary organic synthesis, as wimessed by a number of cascade processes developed in the past decade [1]. The great success is attributed to two unique interconveilible activation modes, enamine [2] and iminium activations [3]. Enamine catalysis has been widely applied to the a-functionalizations of aldehydes and ketones. Mechanistically, dehydration between a chiral amine and the carbonyl of an aldehyde or ketone generates an intermediate, 2, which undergoes an enantioselective a-substitution or nucleophilic addition reaction to produce respective iminium intermediate 3 or 5 (Scheme 1.1). Hydrolysis affords the products and, meanwhile, releases the chiral amine catalyst. 

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