Combinatorial chemistry multicomponent reactions

Most of the examples in this chapter deal with one (intramolecular reactions) or two components. With the advent of combinatorial chemistry, multicomponent reactions stitching together three or more building blocks have emerged as potent tools. 

A. V. Zychlinski, in MultiComponent Reactions Combinatorial Chemistry, Z. Hippe, I. Ugi, Eds., pp. 28-30, German-Polish Workshop, Rzeszdw, Sept. 1997 University of Technology, Rzesz6w/Technical University, Munich, 1998, p. 31. 

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 newly available biological high-throughput screening (HTS) systems have induced many initiatives in the field of combinatorial chemistry [42]. Besides oligopeptide syntheses [43], multicomponent reactions offer attractive methods for the production of high-diversity libraries. Passerini and Ugi reactions (Scheme 19) are frequently used for synthesis of libraries containing thousands of compounds [44],... 

Zhang, W. 2007. Fluorous-enhanced multicomponent reactions for making drug-like library scaffolds. Combinatorial Chemistry High Throughput Screening, 10 219-29. 

In combinatorial chemistry, the development of multicomponent reactions leading to product formation is an attractive strategy because relatively complex molecules can be assembled with fewer steps and in shorter periods. For example, the Ugi multicomponent reaction involving the combination of an isocyanide, an aldehyde, an amine, and a carboxylic acid results in the synthesis of a-acyl amino amide derivatives [32]. The scope of this reaction has been explored in solid-phase synthesis and it allows the generation of a large number of compounds with relative ease. This reaction has been employed in the synthesis of a library of C-glycoside conjugated amino amides [33]. Scheme 14.14 shows that, on reaction with carboxylic acids 38, isocyanides 39, and Rink amide resin derivatized with different amino acids 40, the C-fucose aldehyde 37 results in the library synthesis of C-linked fucosyl amino acids 41 as potential mimics of sialyl Lewis. ... 

Tuch, A., Walle, S. Multicomponent reactions. Handbook of Combinatorial Chemistry 2002, 2, 685-705. 

Some examples for the use of multicomponent reactions in combinatorial chemistry are given in Table 3.9. Multicomponent reactions have also been employed in the synthesis of rings (see Section 3.3.11). 

Combinatorial Chemistry begins with a general overview on recent advances in the subject, with expert surveys provided on selected solid-phase organic reactions and - for the first time - also on solution-phase combinatorial chemistry. These chapters are followed by a detailed survey of the broad research into multicomponent reactions. 

Potentially useful heterocyclic libraries can also be prepared by the application of solution-phase combinatorial chemistry. Although multiple reactions in solution have often been complicated by the difficulties with liquid-liquid extractions the introduction of solid scavengers and equipment to automate these extraction processes allows hundreds of reactions to be managed simultaneously. A typical example is a series of aminothiazole derivatives which has been prepared starting from acyclic precursors (Scheme 3.9). Naturally one-pot multicomponent condensations such as the Ugi (library 84) [332], Passerini or Biginelli reactions present one of the simplest... 

A powerful tool to synthesize easily minute amounts of organic compounds on demand by using both ionic liquids droplets as microreactors and electrowetting as a fluidic motor has been described. These droplets can be moved, divided and combined on an open digital microfluidic lab-on-a-chip system [60]. This has been demonstrated with BTS ILs used as reaction media and supports, properly functionalized to perform the Grieco s multicomponent synthesis of tetrahydroquinolines (Fig. 5.5-3). It is assumed that this original concept should impact many areas, notably combinatorial chemistry, parallel synthesis, optimization of protocols, synthesis of dangerous products and embedded chemistry in a portable device. 

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