Carbanionic Friedel−Crafts Equivalents. Regioselective Directed Ortho and Remote Metalation−C−N Cross Coupling Routes to Acridones and Dibenzo[b,f]azepinones

• Published in: Journal of organic chemistry Vol. 73; no. 24; pp. 9710 - 9719
• Main Authors: MacNeil, Stephen L, Gray, Matthew, Gusev, Dmitry G, Briggs, Laura E, Snieckus, Victor
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 19.12.2008; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Organic; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with only one n hetero atom and condensed derivatives; Kinetics and mechanisms; Noncondensed benzenic compounds; Organic chemistry; Physical Sciences; Preparations and properties; Reactivity and mechanisms; Science & Technology; REARRANGEMENT; OXCARBAZEPINE; SUBSTITUTION; GENERAL-ROUTE; DESIGN; IN-VITRO ACTIVITIES; ARYL HALIDES; DOUBLE-BLIND; DERIVATIVES; ALKALOIDS; Kinetic control; Xanthone; Regioselectivity; Nitrogen heterocycle; Acridine derivatives; Theoretical study; Aniline derivatives; Carbanion; Organic halogen compounds; Low energy; Buchwald Hartwig reaction; Amine; Friedel Crafts reaction; Aniline; Cyclization; Cross reaction; Density functional method; Benzenic compound; Benzamide derivatives; Aromatic compound; Metalation; Methylation; Chemical synthesis; Conformation
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo801856n

Carbanion-mediated general regioselective routes to acridones 4 (Table ) and dibenzo[b,f]azepinones 20 (Table ) are described. Buchwald−Hartwig C−N cross coupling of o-halo benzamides 1 with anilines 2 or 16, followed by simple N-methylation, dependably provides N-methyl diarylamines 3 (Table ) and 18 (Table ). Upon treatment with LDA, 3 and 18 are converted into acridones 4 and dibenzo[b,f]azepinones 20, respectively, in good to excellent yields with regioselectivity which depends upon the presence or absence of directed metalation groups (DMGs). Brief investigations as follows are described: the synthesis of desmethyl acridone 15 (Scheme ), an attempt to effect a double-directed remote metalation sequence which leads only to a monocyclization product 13 (Scheme ), and an analogous but nonregioselective route to a xanthone 22 and dibenzo[b,f]oxepinone 24 (Scheme ). DFT calculations reveal low energy conformations for compounds 18b and 23 which account for product formation and indicate that the cyclization reactions are under kinetic control.