Multicomponent reactions enantioselective

One way to gain fast access to complex stmctures are multicomponent reactions (MCRs), of which especially the isocyanide-based MCRs are suitable to introduce peptidic elements, as the isonitrile usually ends up as an amide after the reaction is complete. Here the Ugi-4 component reaction (Ugi CR) is the most suitable one as it introduces two amide bonds to form an M-alkylated dipeptide usually (Fig. 2). The Passerini-3CR produces a typical element of depsipeptides with ester and amide in succession, and the Staudinger-3CR results in p-lactams. The biggest unsolved problem in all these MCRs is, however, that it is stUl close to impossible to obtain products with defined stereochemistry. On the other hand, this resistance, particularly of the Ugi-reaction, to render diastereo- and enantioselective processes allows the easy and unbiased synthesis of libraries with all stereoisomers present, usually in close to equal amounts. 

Guillena G, Ramon DJ, Yus M (2007) Organocatalytic enantioselective multicomponent reactions (OEMCRs). Tetrahedron-Asymmetry 18 693-700... 

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]. 

Discovered in the middle of the 19th century, the Strecker reaction is one of the earliest atom-economic multicomponent reactions. Amino nitriles were simply obtained from ammonia, hydrogen cyanide and an aldehyde. These products are important intermediates for the synthesis of natural and unnatural a-aminoacids. Due to the ever-increased demand for enantioenri-chied a-aminoacids, the asymmetric Strecker reaction has emerged as a viable synthetic method. Since the first report published in 1996, the catalytic enantioselective cyanation of preformed imines was intensively studied and several excellent reviews were devoted to this topic. ... 

The first multicomponent reaction was the Strecker reaction reported in 1850 by Adolf Strecker [241aj. It is a three-component coupling between carbonyl derivatives, amines, and cyanide source, such as hydrogen cyanide, to provide a-aminonitriles which constitute potent starting materials to achieve important a-amino acids by simple hydrolysis. The mechanism of the Strecker reaction involves the initial formation of an imine from condensation of the amine component to the carbonyl component, after which addition of the cyanide component to this imine intermediate follows. Although the first enantioselective, metal-catalyzed Strecker... 

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. 

In the intensively studied field of multicomponent reactions (MCRs), one can highlight several interesting cascades involving successive C-N and C-C bond formations. It is important to note that, although the majority of these sequences such as the Hantzsch, the Biginelli, or the Mannich reactions are known for more than one century, their organocatalytic enantioselective versions have been disclosed only very recently. 

For selected reviews on organocatalyzed MCRs, see (a) G. GuiUena, D. J. Ramon, M. Yus, Tetrahedron Asymmetry 2007, 18, 693-700. Organocatalytic enantioselective multicomponent reactions (OEMCRs). (b) H. PeUissier, Adv. Synth. Catal. 2012, 354, 237-294. Recent developments in asymmetric... 

As initially stated, the definition of multicomponent reaction could be extended also to those reactions that implicate the addition of further reagents only after a suitable time from the very beginning of the procedure. Among others, few Chinese groups reported two notable examples of one-pot Michael addition/Pictet-Spengler cyclization sequence. In particular, in 2011, Zhao et al. developed a high enantioselective organocatalytic synthesis of several... 

Y. Su, M. J. Bouma, L. Alcaraz, M. Stocks, M. Furber, G. Masson, J. Zhu, Chem.-Eur. J. 2012, 18, 12624-12627. Organocatalytic enantioselective one-pot four-component Ugi-type multicomponent reaction for the synthesis of epoxy-tetrahydropyrrolo [3,4-h]pyridin-5 -ones. 

In the context of enantioselective nickel-catalysed multicomponent reactions, many excellent results have also been achieved. For example, three-component reactions between 1,3-dienes, carbonyl compounds... 

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