1.3- Benzazepinone system

The cyclization of aryl iodide 322 with a Pd(0) catalyst and thallium acetate provides a convenient approach to the 1,3-benzazepinone system 323 (Scheme 174) <1998ICA123, CHEC-III(13.08.4.1.3)249>. 

A second approach to the indolo[3,2-c /]benzazepinone system was also reported in 2005 by Joseph and coworkers. This involved a neat route based on 3-substituted indole derivatives and an intramolecular Heck coupling to form the 12a-12b bond in the fused ring system <05TL8177>. 

Several condensed 6-7 bicyclic systems have been prepared from AAs. Some Af -chloroacetylated AAs are photochemically transformed into heterocycles with a condensed seven-membered ring. For example, A-chloro-acetyl-D,L-w-tyrosine is easily cyclized into benzazepinone 109a on irradiation with a high-pressure mercury lamp (67JA1039 68JA776). 

A-(2-Hydroxybenzoyl)-AA, prepared from salicylaldehyde and an AA, when reduced and cyclized with TFAA, afforded l,3-oxazolo[2,3-h][l,3]be-nzoxazinones 128 as a new heterocyclic system [93H(36)2811]. In another group of AAs, the methyl group is transformed into a methylene group to give a benzazepinone derivative. From Met ester the cis and trans isomers of compound 129 were obtained in a 48 52 ratio (92CB2467). 

Reaction of the o-aminophenylbutanol 108 with a new rhodium-based catalytic system (Cp = pentamethylcyclopentadienyl) 109 in the presence of K2CO3 gave the tetrahydro-l-benzazepinone 110 in 86% yield (Equation 13). This represents one of the few methods for direct catalytic cyclization to this system <2004OL2785>. 

Two approaches to the 2-benzazepine system, in particular the 2-benzazepinone 142, have been reported by Le Diguarher et al. The first started from (acid-catalyzed cyclization to 141 N-alkylation and carbamate deprotection then afforded 142. The second route was based on A-HOC aminomalonate 144 and 2,2 -dibromo-o-xylene, and then steps via 145 and... 

Access to the 1,3-benzazepinone 39 has been achieved from aryl iodide 38 with a Pd(0) catalyst, followed by cyclization of the intermediate palladium complex upon reaction with thallium acetate, thus providing a convenient approach to the fused seven-membered ring system (Equation 5) <1998ICA(270)123>. 

Several approaches to the synthesis of the tetrahydrobenzazepine ring system have been described, and excellent methods exist for the preparation of aryl substituted tetrahydrobenzazepines. However, benzazepines that are either unsubstituted or alkyl-substituted on the azepine ring are much less readily obtainable. For instance, the benzazepinone, synthesized by this procedure, was originally isolated, in tow yield, from the mixture of photoproducts obtained from the irradiation of N-[3-(3,4-dimethoxyphenyl)]propyl chloroacetamide. Preparative approaches to the benzazepinones have required multiple steps starting from an N-phenylethylacetamide and involving chloromethylation, cyanide displacement, nitrile solvolysis, hydrolysis to the amino acid and cyclization.7 The f-alkyl derivatives are... 

Nicholls, I.A., Craik, D.J. and Alewood, P.F. (1994) NMR and molecular modelling based conformational analysis of some N-alkyl l-and 2-benzazepinones useful central nervous system agent design motifs. Biochem. Biophys. Res. Comm. 205 98-104. 

---