Novel aminocatalytic and photochemical reactions

Identifier:  TDX:2537

Handle: https://hdl.handle.net/20.500.11797/TDX2537

Authors:  Nappi, Manuel

Abstract:
Asymmetric aminocatalysis has allowed to develop the hitherto elusive catalytic asymmetric Diels-Alder reaction of in situ generated ortho-quinodimethane intermediates. The indole-2,3-quinodimethane strategy, originally conceived for the straightforward synthesis of indole alkaloids more than 30 years ago, can now be made catalytic with a chiral secondary amine. This strategy can then be used to synthesize a structurally diverse range of complex nitrogen-contain compounds and spirooxindole-containing tetrahydrocarbazoles with high chemical yields and excellent stereoselectivities. The potential of aminocatalytic indole-2,3-quinodimethane strategy can be expanded to include a variety of different dienophiles. The implementation of a multicatalytic, one-pot Diels-Alder/benzoin reaction sequence, based upon the unprecedented combination of trienamine and carbene catalysis, led to the highly stereoselective preparation of complex tetrahydrocarbazole derivatives. The asymmetric organocatalytic aza-Michael reaction via dienamine activation of the nucleophilic nitrogen has been studied. Self-assembly organocatalysts, such as the combination of (R) 2-indoline carboxylic acid and 9-epi-quinine squaramide derivative, was recognized as the best catalytic system for this challenging addition. Indazole was chosen as model nucleophilic partner due to its acidity and ability to form the N-centered dienamine. The direct β-aldol reaction between cyclic ketones with aryl ketones has been achieved via the synergistic combination of photoredox catalysis and organocatalysis. Diaryl oxymethyl or aryl−alkyl oxymethyl radicals, transiently generated via single-electron reduction of ketone precursors, readily combine with β-enaminyl 5πe– radical key species, generated by photon-induced enamine oxidation, to produce γ-hydroxyketone adducts. Finally, an operationally simple protocol for the direct aromatic perfluoroalkylation and trifluoromethylation of α-cyano arylacetates has been reported. This metal-free approach, which occurs at ambient temperature and under visible-light irradiation, is driven by the photochemical activity of electron donor–acceptor (EDA) complexes, formed in situ by the interaction of transiently generated enolates and perfluoroalkyl iodides.