Formal [4+2] Cycloaddition of o‐Aza‐Quinone Methide for the Synthesis of 1,4‐Heterocycle‐Fused Quinolines

Abstract

A protocol involving intramolecular formal [4 + 2]-cycloaddition of in situ generated o-azaquinone methide for the facile synthesis of 1,4heterocycle-fused quinoline motifs is demonstrated. The cascade involved tandem CÀ O, CÀ C, and CÀ N bond formation and also exhibited excellent functional group tolerance. Enantiomerically enriched 1,4-oxazepino quinolines were synthesized using alkynols derived from L-amino acids. The sulfoxide embedded quinolines were transformed to pentacyclic 1,4-thiepino tethered indeno-quinoline scaffolds via Pummerer cyclization.

2-Azidobenzaldehyde-Based [4+2] Annulation for the Synthesis of Quinoline Derivatives

“…Other than aniline-based [3+3] annulation [ 137 ] and [4+2] annulation [ 138 ] reactions for making 4-hydroxyquinolines, 2-azidobenzaldehydes have also been employed for the [4+2] annulation-based synthesis of 4-alkoxy quinolines. Gharpure and coworkers reported the reactions of 1 with hydroxyalkynes for the synthesis of different kinds of 4-alkoxy quinolines, 107 , 108 , and 109 ( Scheme 22 ) [ 139 , 140 , 141 ]. The synthesis first led to the formation of oxonium ions 110 followed by intramolecular [4+2] cycloaddition and aromatization to give 4-alkoxy quinolines 109 , with a new seven-membered heterocyclic ring ( Scheme 22 ).…”

Recent Advances in the Synthesis of Fused‐Cyclic Quinolines

“…An ingenious approach for the construction of seven fused membered fused quinoline has been documented via the two‐component reaction of heteroatom tethered alkynols 288 and o ‐azido benzaldehyde 289 by Gharpure group (Scheme 92). [182] In this reaction, synthesis of 1,4‐dioxepino and 1,4‐oxathiepino quinolines 290 proceed through intramolecular formal [4+2]‐cycloaddition of in situ generated o ‐aza‐quinone methides. Utilizing trimethylsilyl trifluoromethanesulfonate as a Lewis acid catalyst is one of positive aspect of this strategy.…”

1,2-Difunctionalizations of alkynes entailing concomitant C–C and C–N bond-forming carboamination reactions

“…On similar lines, they also applied the developed strategy for the synthesis of 1,4-heterocycle-fused quinoline motifs 130 from hetero-atom tethered alkynols 131 ( Scheme 73 ). 88 Various enantiopure 1,4-oxazepino-quinolines were synthesized in good yield from the corresponding amino acid-derived alkynols. Further, O / S -tethered alkynols were employed in the reaction to synthesize dioxepino/oxathiepino-quinolines.…”