The Discovery of New Isocyanide-based Multicomponent Reactions

MCRs of up to seven different starting materials have been described in the past [3]. MCRs have numerous advantages over classical approaches (linear, iterative or divergent synthesis) in assembling useful chemical products. The advantage of convergence over a divergent synthetic approach is well appreciated in the syn- 

Multicomponent Reactions. Edited by Jieping Zhu, Hugues Bienayme Copyright 2005 WILEY-VCH Verkg GmbH Co. KGaA, Weinheim ISBN 3-527-30806-7 

Typically MCRs allow the synthesis of very many derivatives of a special scaffold. Since the number of possible products increases exponentially with the multiplicity of the MCR, very large chemical spaces can be inspected. These very large chemical spaces are not realistically accessible by classical sequential syntheses. As realized by Ugi in 1961 starting with 1000 each of the educts carboxylic acid, amines, aldehydes and isocyanides 10004 products are accessible [4]. In this seminal paper the roots of combinatorial chemistry are described. The authors noted that MCRs have huge variability. Although the paper describes the essentials of combinatorial chemistry, the time was not right for the great advances that only started 30 years later. 

MCRs are now no longer confined to a few backbones, but hundreds of easily accessible chemical scaffolds have been described and the description of novel scaffolds available through MCRs is a very active area in the organic-chemical literature. Thus MCRs have become very popular in all areas of organic chemistry and especially in applied chemistry, such as the discovery of novel biologically active compounds as drugs or agricultural chemicals, and material sciences. 

Overall MCRs are a big step towards the ideal synthesis, which, according to Wender et al. can be measured by parameters such as the step count, overall yield, selectivity, cost, scale, resource requirements, waste stream, development time, execution time and personnel [8], The discovery of novel IMCRs are explained and several conceptually different approaches towards this goal, with an emphasis on our recent contributions in this area are shown. 

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