Versatile Synthesis of Dihydroquinolines and Quinoline Quinones Using Cyclobutenediones. Construction of the Pyridoacridine Ring System

Abstract

1-BOC-2-lithio-1,4-dihydropyridines were condensed with 3,4-disubstituted cyclobutenediones to produce 1,2-adducts. Neat thermolysis under oxygen-free conditions produced substituted 1,4-dihydroquinoline hydroquinones in which the tert-butoxy residue of the BOC group was displaced by a phenolic residue, generating an oxazolone ring that functioned to protect both rings of the dihydroquinoline hydroquinone from untimely oxidation. Oxidative aromatization with concomitant loss of the oxazolone ring was achieved using 2 equiv of o-chloranil in acetic acid and provided substituted quinoline quinones in good yields. By use of this strategy, a concise synthesis of the pyridoacridine ring system was achieved.

Recent developments in the chemistry of dihydropyridines

“…Metallation of the α-position of N-alkoxycarbonyl-1,4-dihydropyridines allowed the introduction of squaric acid based electrophiles, and the resulting addition compounds were subjected to thermolysis to afford the corresponding dihydroquinolines. 171 In a different approach, interaction of a related 2-lithio-1,4dihydropyridine with hexacarbonylchromium followed by methylation, gave a dihydropyridine Fischer carbene complex, which was reacted with alkynes, in a useful benzannulation, to produce similar dihydroquinolines. 172 The 2-methyl substituent of a Hantzsch-type dihydropyridine was efficiently metallated, and the organolithium derivative thus formed was quenched with different electrophiles (alkyl halides, acetone, TMSCl, disulfides and Davis' oxaziridine) to furnish the modified/functionalized dihydropyridines at this position.…”

One-Step Synthesis of Substituted α-Pyrones from Cyclobutenediones and LithiatedO-Silyl Cyanohydrins

“…The addition of unsaturated nucleophiles to cyclobutenediones provides access to, inter alia, quinones and phenols, − ring-fused α-pyridones, and quinoline/isoquinoline quinones. , In an effort to extend this highly versatile chemistry to the synthesis of substituted α-pyrones, the addition of a lithiated O -silylated cyanohydrin to a cyclobutenedione with subsequent intramolecular 1,4-silyl migration and displacement of cyanide was envisioned. This process would generate in situ a 4-acylcyclobutenone, which is known to undergo facile rearrangement to a substituted 2-pyrone (eq 3) …”

New Convenient One-Pot Methods of Conversion of Alkynes to Cyclobutenediones or α,β-Unsaturated Carboxylic Acids Using Novel Reactive Iron Carbonyl Reagents

“…It is well-known that cyclobutenediones and their adducts are highly versatile starting materials for the synthesis of substituted naphthalenes, phenols, catechols, heterocycles, and polycyclic aromatics . It has been also reported that cyclobutenediones might show some biological activity .…”