Synthesis Of Isoquinolinones And Isoindolinones Via Multicomponent Reactions

Multicomponent reactions(MCRs) serve as a powerful tool in recent years for assembly of complex structures from simple starting materials. These highly effect reactions are widely used in both combinatorial synthesis and are particularly useful for the construction of diverse nature products due to the advantages of greater bonding-efficiency, atom economy and structural complexity.Isoquinolinones constitute an important class of alkaloids, which displays important biological activities including vasorelaxation, cardiotonic effects, reduse blood press, antiglycuresis and anticancer effects. The isoindolinones contain the scaffold in many compounds of the natural products and exhibit an array of promising biological and pharmacological properties. It is the most important to find a methodology which constitutes the most simple and direct high-yield approach to a variety target molecules because of the potential application prospect.This paper lay emphasis on the syntheses of five and six-numbered heteroaromatic compounds without metal catalysis. The synthesis accomplished via the three component reaction of 2-acetyl-oxirane-2-carboxamides, arylaldehydes and malononitrile at room temperature using DCM as the solvent. We found that two entirely different product can be got from cis- and trans- substrates by changing the type of the base and extend the time, isoquinolinones and isoindolinones. Based on all the experiment results, we proposed the plausible mechanism: for the formation of isoquinolinones, The process involves tandem Knoevenagel condensation,intermolecular Michael addition, intramolecular carbo-cyclization(to form the six-membered carbon ring), aromatization via elimination of the cyanide anion and intramolecular azacyclization(to form the six-membered nitrogen ring); for the synthesis of isoindolinones, except undergos the same progress, it may also contain hydrolysis, decarbonation and recyclation. One six-numbered carbon ring and one five-numbered/six-numbered nitrogen ring were formed in this multicomponent reaction, in addition, this reaction highly effect construct 4 C-C bond and 1 C-N bond.All of the new conpounds were characterized by 1HNMR spectra, 13 CNMR spectra,High resolution mass spectra(HMRS) and the X-ray single-crystal diffraction. This is the new synthesis method of heterocyclic compounds.