Benzo azepinone

Few examples of the intramolecular electrophilic substitution on a C2py oie site have been reported for benzo[/]pyrrolo[l,2-a]azepinones. Thus, treatment of acid 62 with phosphorous pentachloride results in Friedel-Crafts product 63 (Scheme 13 (2000T9351)). 

Similarly, benzo[/]pyrrolo[l,2-a]azepinone 68 (R = Ph X = CH2) can be obtained from the corresponding acid 67 via intramolecular Friedel-Crafts acylation (Scheme 14 (2002JMC4276)). 

Intramolecular electrophilic reactions of substituted pyrrole-2-carboxylic acids or their amides lead to benzo[d]pyrrolo[l,2-a]azepinones. Acid 70 in this fashion undergoes Fiiedel-Crafts cyclization to furnish fused azepine 71 in good yield (Equation (6) (2000JOC2479)). 

Several azepine ring constructions have been reported using palladium catalyzed C-C bond formation. Palladium catalyzed cyclizations of substituted tryptamine derivatives 73 lead to benzo[d]pyrrolo[l,2-a]azepinones 74 (Equation (8) (2000JMC1050)). 

Reaction of the radical derived from substituted 2-bromo indole 78 leads in moderate (37%) yield to benzo[d]pyrrolo[l,2- ]azepinone 79 along with 32% of the reduction product 80. The process occurs via radical addition to the benzene ring followed by rearomatization (Equation (9) (2000TL4209)). 

Synthesis of benzo[e]pyrrolo[l,2-a]azepinone 82 was accomplished by palladium catalyzed ring closure of ketone 81 (Scheme 16 (2005JMC1705)). 

Palladium catalyzed reaction of iodo 84 with allene is an example of a 5 + 2 ring formation and gives access to the fused benzo[d]pyrrolo[l,2-fl]azepinone... 

A benzolog of 1 //-naphtho[o/]azepine-2-one 506 is obtained by cy-clization of l-(2 -amino)phenyl-8-methoxycarbony [naphthalene 505 (71AJC835). The reduction of azepinone 506 to azepine 507, followed by dehydrogenation with dichlorodicyanobenzoquinone (DDBQ) leads to benzo[/]naphtho[crf]azepine 508. The latter compound easily adds water, alcohol, or amines to a C=N bond, resulting in adducts 509, whereas treatment with perchloric acid gives rise to perchlorate 510 (71AJC835). 

Indole-fused, or indole-benzo-fused azepinone derivatives have attracted synthetic attention and examples include the preparation of 85 in 84% yield from 84 by intramolecular Heck coupling [01SL848], as well as the preparation of paullone 87 (a CDK inhibitor) by cyclisation of 86 under basic conditions borylation/Suzuki coupling technology was used to access 86 [02JOC1199]. Acid-catalysed cyclisation with polyphosphoric acid was used to prepare the racemic reduced azepino[4,5-6]indoles 92a,b from the precursors 91, which were obtained in turn from CDl-mediated coupling of 88 and 89, followed by reduction of the amide with lithium aluminium hydride [01H1455]. 

Oh and Reddy succeeded in developing Rh-catalyzed intramolecular benzannu-lation by use of o-alkynylbenzaldehydes 71, which have a pendent nitrile group, leading to isoquinoline derivatives 72 (Scheme 15.29). Interestingly, the substrate having no gem diester on the tether gave benzo[c]azepinone derivatives exclusively but not isoquinoline frameworks [41],... 

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