Multi-component reactions and related chemistries

Abstract

Multi-component reactions (MCRs) is one of the oldest fields in organic chemistry, which has rapidly grown during the past two decades after a relative inactive period. The first synthesis of organic molecules via MCR was published in 1850 by Strecker. Then in 1917 the first example of the use of MCR for natural product synthesis appeared with the synthesis of the alkaloid tropinone via Robinson’s synthesis. The most active period in the development of the classical MCR chemistry was in the 1960s when the research groups of Ivar Ugi and Ulrich Schoellkopf (Germany) and Albert van Leusen (Netherlands) discovered isocyanide-based MCRs. Now these reactions have become powerful tools for the synthesis of peptides, pyrroles, imidazoles and indoles. However, for quite sometimeMCR chemistry was considered exotic in organic synthesis and its development plateaued. The situation changed with development of parallel synthesis, combinatorial chemistry and high-throughput experimentation. The number of research groups active in theMCR field grew rapidly in the past 10 years, and novel MCRs are being discovered just about every week resulting in several hundreds publication per year. Now more and more companies include MCR chemistry in their synthetic arsenal because (1) these chemistries are fully amenable to automation since there is no need to isolate intermediates and the reactions can be carried out in single reaction vessels, and (2) MCRs are more convergent based on a sequence of uniand bimolecular reactions. In addition, MCRs are a particular case of reaction networks, which can be considered as a model of natural processes and prebiotic evolution, and new possibilities for MCR development appeared with the