Direct access to tetrasubstituted cyclopentenyl scaffolds through a diastereoselective isocyanide-based multicomponent reaction

An efficient strategy combining the stereocontrol of organocatalysis with the diversity-generating character of multicomponent reactions is described to produce structurally unique, tetrasubstituted cyclopentenyl frameworks. An asymmetric Michael addition-hemiacetalization between alpha-cyanoketones and alpha,beta-unsaturated aliphatic aldehydes was performed for constructing cyclic hemiacetals, which were next employed as chiral bifunctional substrates in a new diastereoselective intramolecular isocyanide-based multicomponent reaction. This approach furnished a diversity of structurally complex compounds - including peptidomimetics and natural product hybrids in high stereoselectivity (up to >99% ee and up to >99 : 1 dr) and in moderate to high yields.

Automated summary

An efficient strategy combining stereocontrol of organocatalysis with diversity-generating character of multicomponent reactions was used to produce structurally unique, tetrasubstituted cyclopentenyl frameworks. This approach yielded a diversity of structurally complex compounds with high stereoselectivity and moderate to high yields, including peptidomimetics and natural product hybrids.