Multicomponent reactions advantages

To fully use the advantages afforded by multicomponent reaction systems in solid-phase organic synthesis, strategies in which each component is immobilized on the resin must be devised. In this way, individual components can be explored in terms of diversity without the restrictions imposed by immobilization. We have described solid-phase Mannich reactions1 of a resin-bound alkyne (see chapter 5), and we show here that the diversity of products using this chemistry can be enhanced when a different component of the reaction system is immobilized. Specifically, a secondary amine, piperazine, is bound to a resin and then treated with... 

The multicomponent reactions have been widely used in solid and solution-phase chemistry during the last years. Multicomponent reaction strategies offer significant advantages compared with conventional liner type syntheses. Three or more reactants come together in a one pot reaction to form new products that contain portions of all the components [281]. There are several well-known multicomponent reactions that have been used in combinatorial chemistry. 

The combination of the two approaches that have obvious advantages therefore presents an attractive reaction design with added value in the inventions and optimizations of existing processes. We hereby give an overview of current achievements in this field. However, there is a rather limited number of published data on strictly defined multicomponent reactions in which aU the reactants are added at once to the reaction mixture, due to the technical characteristics of the systems (e.g. number of inlets) or the possible complications due to side reactions such reactions are conducted in a multistep mode or employ preformed intermediates. These reactions are also taken into account on the condition that the process is conducted continuously without purification of the intermediates and that the final product contains scaffolds originating from three or more starting molecules. 

In line with the tremendous renewed activity witnessed in recent years in the field of multicomponent reactions, remarkable new strategies have been developed based on metal-catalyzed coupling processes. Advances in this area take advantage of the myriad of bond-forming processes that can be achieved with metal catalysts. 

The basic methods of the identification and study of matrix-isolated intermediates are infrared (IR), ultraviolet-visible (UV-vis), Raman and electron spin resonance (esr) spectroscopy. The most widely used is IR spectroscopy, which has some significant advantages. One of them is its high information content, and the other lies in the absence of overlapping bands in matrix IR spectra because the peaks are very narrow (about 1 cm ), due to the low temperature and the absence of rotation and interaction between molecules in the matrix. This fact allows the identification of practically all the compounds present, even in multicomponent reaction mixtures, and the determination of vibrational frequencies of molecules with high accuracy (up to 0.01 cm" when Fourier transform infrared spectrometers are used). 

A major advantage of the non-Lewis acid catalyzed cycloaddition is the possibility of carrying out the domino [4 + 2]/[3 + 2] cycloaddition in a one-pot fashion, since electron-poor alkenes react much faster with the nitronate formed in situ than electron-rich alkenes [14c, 20, 21[. This multicomponent reaction then provides the nitroso acetals in a single transformation, without the need to isolate the nitronate which was formed first, prior to the 1,3-dipolar cycloaddition. 

As many of the classical multicomponent reactions, the Strecker synthesis also takes advantage of the versatile chemistry of the initially formed imine. The formation of the amino nitrile, however, is reversible under the reaction conditions which usually results in lower yields. This problem was elegantly solved in the Bucherer-Bergs variation,3 4-376 where the initially formed aminonitrile is irreversibly trapped by formation of a hydantoin as depicted in Scheme 1.8 (entry b). 

Multicomponent reactions are particularly viable procedures for combinatorial synthesis. The clear advantage of conducting these reactions on solid supports lies in the fact that all nonpolymer-bound components (e.g. excess of reagents) can simply be removed. 

Multicomponent reactions (MCRs) have attracted much attention in the past decade because of advantages such as high atom economy, simple procedure, and high efficiency. [1] Because of their ability to generate complex structures economically and efficiently [2], numerous MCRs have been developed and widely studied, such as the Cu-catalyzed three-component reactions [3-6], Mannich reactions [7, 8], Passerini reactions [9, 10], and A3-coupling reactions [11]. Of these, multicomponent alkyne reactions have become quite popular recently and abundant literature has been published regarding the various MCRs of alkynes with all sorts of reactants [12, 13]. 

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