Combinação de reações organocatalíticas e multicomponentes para a síntese de sistemas heterocíclicos e moleculas híbridas
Abstract
Small enantiomerically pure or enriched organic molecules are key starting materials
in organic synthesis. Chiral building blocks are in high demand in the overall
synthesis of complex natural products and in the discovery and development of drugs
as well as in the production of advanced pesticides, fragrances and materials. In this
sense, organocatalytic methodologies have emerged as a third pillar of asymmetric
catalysis and have a prominent position in the development of more sustainable
methods. Similarly, multicomponent reactions (MCRs) present themselves as a
powerful tool for the synthesis of bioactive heterocyclic compounds and analogues of
natural products. Chiral aldehydes are key components in stereocontrolled MCRs,
methods for the asymmetric functionalization of carbonyl compounds are relevant for
the development of novel multicomponent stereoselective approaches.
In recent years, our group and the Banfi group have been exploring the potential of
organocatalysis to generate compounds enantiomerically enriched with the synthetic
power of MCRs in the diversification of these chiral compounds.
In this work we describe a highly stereoselective methodology for the synthesis of
natural product hybrids from an organocatalytic tandem procedure, followed by a
multicomponent reaction. Effectively, the procedure comprises an organocatalysed
conjugate addition of active methylene compounds (1,3-dicarbonyls and α ester or
cyanoketones) to α,β-unsaturated aldehydes to form asymmetric hemiacetals
containing orthogonal functional groups. Next, an isocyanate based intramolecular
multicomponent reaction is implemented. Through the use of this approach it was
possible to synthesize hybrids of natural products, including up to four different
molecular fragments, such as hydroquinoline, tetrahydropyridine, peptides, lipid and
glycoside units