STEREOSELECTIVE HETEROCYCLE SYNTHESIS COUPLING MULTICOMPONENT REACTIONS WITH BIOCATALYSIS OR ORGANOCATALYSIS

Isocyanide-based multicomponent reactions (IMCRs) are a very useful tool for the rapid assembly of libraries of drug-like heterocycles, with the introduction of 3-4 diversity inputs. However, the stereocontrolled obtainment of complex products endowed with several stereogenic centres is still challenging because of: a) scarce availability of enantiomerically pure chiral components; b) their easy racemization/epimerization during the IMCR; c) low diastereoselectivity of the multicomponent step; In order to overcome in part these problems, some examples of a general approach that combines IMCRs with biocatalysis or organocatalysis will be reported. The strategy involves three stages: a) enantioselective generation (also in a diversity-oriented manner) of chiral inputs via biocatalysis or organocatalysis; b) use of these inputs in diastereoselective IMCRs; c) final cyclization to heterocycles. In this way, a variety of complex stereochemically pure heterocycles are accessed in few steps.