Direct access to tetrasubstituted cyclopentenyl scaffolds through a diastereoselective isocyanide-based
Vitor A Fernandes1, Rafaely N Lima1, Yoisel B Broterson1
1Centre of Excellence for Research in Sustainable Chemistry (CERSusChem), Department of Chemistry, Federal University of São Carlos São Carlos São Paulo 13565-905 Brazil mwpaixao@ufscar.br.
Abstract:
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 α-cyanoketones and α,β-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.
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