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

Abstract

N-Benzyl-2-chloro-N,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[b]­pyrrole-2,3-diones, and 1-azaspiro[4.5]­deca-3,6,9-triene-2-ones via the C­(sp2)–C­(sp2) bond formation in the first case and C­(sp2)–C­(sp3) 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 N-benzyl-2-chloro-N,3-diaryloxirane-2-carboxamides with CF3CO2H or AcOH/H2SO4. 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 N-benzyl-2-chloro-N,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(1H)-ones showed that there are three competing reaction channels: (a) ring-closure via the ipso site, (b) ring-closure via the 1,2-Cl shift, and (c) ring-closure via the ortho site. Such mechanistic insights enabled an effective one-pot gram-scale synthesis of viridicatin from benzaldehyde and 2,2-dichloro-N-(4-methoxybenzyl)-N-phenylacetamide.

Visible Light‐Induced Metal‐free Arylation of Coumarin‐3‐carboxylates with Arylboronic Acids

“…[8c] In addition, Hepatitis B inhibitor (8 fa) was also synthesized in 83 % yield from the arylated product i. e. isopropyl 6-chloro-2-oxo-4-phenyl-1,2-dihydroquinoline-3-carboxylate 8 f which was synthesized using this methodology. [23] To substantiate the mechanism, we conducted a control experiment using a radical scavenger TEMPO (2.5 equiv). Indeed, the reaction did not proceed under above conditions (Scheme 4).…”

AlCl3-Promoted Intramolecular Indolinone-Quinolone Rearrangement of Spiro[indoline-3,2′-quinoxaline]-2,3′-diones: Easy Access to Quinolino[3,4-b]quinoxalin-6-ones

“…Based on the results obtained (Table ) and previous literature data, the DFT-computed reaction free energy profile (at 200 °C and 1 M concentration) at the PW6B95-D3/def2-TZVP + COSMO-RS // TPSS-D3/def2-SVP + COSMO level in acetic acid solution is depicted in Scheme . Initially, the dimeric Lewis acid(AlCl 3 ) 2 gets coordinated to the lone pair of C3′ carbonyl oxygen of spiro­[indoline-3,2′-quinoxaline]-2,3′-diones 5g , which is thereby activated, to form the donor–acceptor complex A in a −14.1 kcal/mol exergonic step.…”