Synthesis and Mechanistic Insights of the Formation of 3-Hydroxyquinolin-2-ones including Viridicatin from 2-Chloro-,3-diaryloxirane-2-carboxamides under Acid-Catalyzed Rearrangements.

-Benzyl-2-chloro-,3-diaryloxirane-2-carboxamides, easily obtained from aromatic aldehydes and anilides of dichloroacetic acid under Darzens condensation conditions, proved to be excellent starting compounds for the synthesis of 3-hydroxyindolin-2-ones, cyclohepto[]pyrrole-2,3-diones, and 1-azaspiro[4.5]deca-3,6,9-triene-2-ones via the C(sp)-C(sp) bond formation in the first case and C(sp)-C(sp) bond formation in the second and third cases. Under optimized reaction conditions, 3-hydroxyindolin-2-ones are obtained in a one-pot process, which involves the treatment of -benzyl-2-chloro-,3-diaryloxirane-2-carboxamides with CFCOH or AcOH/HSO. In the case of intramolecular cyclization, the detailed reaction channels depend strongly on the substituents present in the anilide component and in the aromatic ring of the aldehyde component of -benzyl-2-chloro-,3-diaryloxirane-2-carboxamides, as well as the temperature and duration of the reaction. A combined experimental and DFT mechanistic study of the formation of 1-benzyl-3-hydroxy-4-arylquinolin-2(1)-ones showed that there are three competing reaction channels: (a) ring-closure via the site, (b) ring-closure via the 1,2-Cl shift, and (c) ring-closure via the site. Such mechanistic insights enabled an effective one-pot gram-scale synthesis of viridicatin from benzaldehyde and 2,2-dichloro--(4-methoxybenzyl)--phenylacetamide.