Tandem sequences multicomponent reactions

Due to their high atom economy, multicomponent reactions have emerged with a high potential in the fine chemicals and pharmaceutical industries [41]. These reactions are usually not concerted rather, they are tandem or domino processes in which multiple reactions are combined into one synthetic operation. This significantly reduces reaction time as well as the amount of waste in comparison to an alternative multistep synthetic process. The first step produces an intermediate that need not be isolated, but it must undergo a sequence of reactions until the stable... 

Reactions that succeed the hydroformylation can be conducted in a separate step by using entirely different reaction conditions. Alternatively, a multi-reaction sequence can be performed in one pot by using the same reaction regime or different ones. Such transformations belong to domino reactions, multicomponent reactions, or tandem reactions. Especially in the last years, tandem reactions came in the focus of synthetic chemists. In the best case, a single catalyst mediates not only hydroformylation but also the other reactions, and we can call it auto tandem catalysis due to a suggestion by Fogg and dos Santos [2]. 

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... 

Other types of multicomponent reactions have also been successfully developed, such as the first practical three-component imino-Reformatsky reaction, and a pseudo-three-component reaction between allenes and isocyanates, providing excellent levels of enantioselectivity. Finally, excellent results were described for several novel enantioselective tandem sequences. For example, very high enantioselectivities were reached in tandem Michael/ intramolecular cyclisation sequences, as well as in a remarkable multicat-alytic Michael sequence occurring between enones, alkynes, and DIBAL, which stereoselectively afforded a range of chiral p-alkenyl ketones bearing an all-carbon-substituted quaternary stereogenic centre in excellent enantioselectivities. 

The great majority of radical cascades involve sequences of intramolecular steps where the overall propagation is a unimolecular process (with the exclusion of the initiation and termination steps), and recent overviews are given in Refs 1-5. However, meanwhile many tandem reactions involving both intra- and intermolecular steps, as well as multicomponent tandem reactions, have been reported in the literature, which are compiled in recent reviews. " ... 

The radical carbonylation of an alkyl iodide in the presence of Kim s sulfonyl oxime ethers [58, 59, 60] provides a new type of multicomponent coupling reaction where plural radical Cl synthons are consecutively combined [61]. In the transformation, allyltin was used to serve as a trap of benzenesulfonyl radical which converts sulfonyl radical to a tin radical, thus creating a chain. Scheme 14 illustrates such an example, where the product was easily dehydroxylated to give the corresponding tricarbonyl compound on treatment with zinc/AcOH. The radical acylation reaction by Kim s sulfonyl oxime ethers can be conducted under irradiation with the addition of hexamethylditin. This is an alternative path for achieving a similar transformation without the use of photolysis equipment. Scheme 15 illustrates several examples where carbon monoxide and Kim s sulfonyl oxime ethers are successfully combined to create new tandem radical reaction sequences [61],... 

A simple, efficient multicomponent sequence was recently developed to synthesize a-hydroxyalkylpiperidine derivatives from a 4-boronohydrazonodiene, maleimides and aldehydes (Scheme 9.36) [78]. The high diastereoselectivity of these tandem reactions can be explained by a complete endo-selectivity in the first step and a cyclic chair-like transition state in the allylboration reaction. The absolute stereochemistry of the final products can be controlled by using an optically pure l-aza-4-borono-l,3 butadiene. This multi-component reaction can also be realized on a solid support, using an N-arylmaleidobenzoic acid functionalized resin. Very recently, this process... 

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