Meldrum's acid in multicomponent reactions: Applications to combinatorial and diversity-oriented synthesis

In a multicomponent reaction (MCR), one can create multiple new bonds in a single reaction from readily available starting materials; thus, MCRs are resource- and time-effective and therefore economically favorable processes in diversity generation. In contrast, there are MCRs where a multifunctional building block is introduced instead of an additional diversity-holding component, and these can be derivatized using very diverse reactions post-synthetically leading to novel chemotypes. The synthetic applications of Meldrum's acid are focusing primarily on reactions where it is applied as an alternative for acyclic malonic esters. However, its highly acidic character broadened its applications and made it a very useful reagent for MCRs or more precisely in tandem or domino reactions. There are numerous examples reported for the use of the alkylidene conjugates of Meldrum's acid as dienophiles in hetero-Diels-Alder reactions, as well as Michael acceptors. In most cases spontaneous or concomitant post-synthetic derivatization increased its synthetic utility. This minireview gives a non-exhaustive insight into MCRs involving Meldrum's acid, describing various applications in combinatorial and diversity-oriented synthesis.