Multicomponent enantioselective domino reactions

In spite of the explosive development of asymmetric domino processes including multicomponent reactions, domino reactions involving chiral carbohydrate derivatives still remain rare in the literature. It is particularly true with regard to carbohydrate-derived organocatalysts. This section highlights several important works dealing with stereocontrolled domino reactions of chiral carbohydrate derivatives in a first part, and a rare enantioselective domino reaction catalyzed by a chiral carbohydrate derivative in a second part. It must be noted that all the discussed domino reactions are multicomponent ones. 

The field of catalytic enantioselective transformation has blossomed into a mainstay of chemistry. Although many reactions can currently be run with high yields and high enantiomeric excesses (ees), progress still remains to be made in terms of reaction efficiency, atom economy, and environmental safety. While marrying all of these concepts will take time, the development of enantioselective domino and multicomponent reactions certainly represents an important step in this direction [83]. 

This ehapter illustrates how much asymmetric nickel catalysis has contributed to the development of novel enantioselective domino, multicomponent, and tandem sequential reactions. It updates the major progress in the field of enantioselective two- and multicomponent domino reactions as well as tandem sequences promoted by chiral nickel catalysts, covering the literature since the beginning of 2004. It well illustrates the power of these... 

In addition to simple two-component domino reactions based on relay enantioselective multiorganocatalysis, a number of multicomponent reactions have recently been successfully developed. As an example, in 2008... 

In extending this concept to transformations that formally deliver Diels-Alder products, a one-pot three-component Mannich/Michael reaction pathway was developed in which simple cyclic enones, formaldehyde, and aryl amines were treated with catalytic amounts of proline (2) to provide regio-, diastereo-, and enantioselective bicyclic compounds in high yields (Scheme ll.lOb). Multicomponent domino... 

Combinations of enamine-iminium ion activations together with other organo-catalytic activations in asymmetric organocatalytic domino and multicomponent reactions have been developed to achieve the enantioselective consecutive formation of two or more bonds in a stereoselective fashion. 

Sasai has recently described an interesting entry into chiral tetrahydropyridines 37 from acrolein and aromatic tosylimines [29], which involves an enantioselective version of a domino process previously reported by Huang [30] that can be classified as an ABB multicomponent reaction because of the participation of two molecules of acrolein, each of them with a different role in the overall transformation. The best results were obtained with catalyst 36, which contains both Lewis base and Brpnsted acid structural fragments, and the reaction was rationalized as the result of an aza Morita-Baylis-Hillman/aza Michael/aldol sequence (Scheme 3.8). 

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