1 //-Benz azepines synthesis

The synthesis of benzazepines by the acid-catalyzed cyclization of 7 (-(2-arylethyl)-7 (-methyl-2-sulfinylacetamides is a convenient alternative to this acid-catalyzed cyclization. Thus treatment of the amide (172) (Equation (17)) with trifluoracetic anhydride affords the benz(. This method has been used in a first synthesis of the benzopyranobenzazepine alkaloid ( +)-clavizepine <94SL49>. 

Substituted 7,12-dihydroindolo[3,2-c(][l]benzazepin-6(5/0ones 2a and 2b were first reported in 1958 by MacPhillamy et al. [33] as the last intermediate in an 11-step synthesis of 4-ethyl-5,6,7,12-tetrahydro-2-methylindolo[3,2-t/][l]benzazepine. In 1992, Kunick reported the preparation of six indolo[3,2-d][l]benzazepin-6(5/f)ones [34] in a three-step procedure. The crucial step was the decarboxylation reaction of 2,3-dihydro-5-hydroxy-2-oxo-l/7-benz[(t]azepin-4-carboxylic acid ethyl ester into 3,4-dihydro-lH-benz[ ]azepin-2,5-dione, which made possible the subsequent Fischer indole synthesis, with formation of the desired 7,12-dihydroindolo[3,2-fiT [l]benzazepin-6(5/f)ones. 

A combination of ruthenium-mediated isomerisation and ring closing metathesis has been applied to the synthesis of the benz[c]azepine derivative 21 in moderate yield from 20 via 18 and 19 <03SL1859>. 

The alkaloids of the narcotine type can also be synthesized from benz[d]indeno(l,2-f ]azepine (133a) (698) (Scheme 45). Moreover, compound 133a forms a key substance for the synthesis of the tetrahydro-protoberberine (58), protopine (101), rhoeadane (154), and spiroben-zylisoquinoline (191) ring skeletons. The compounds 133a and 133b arise also by rearrangement from the spirobenzylisoquinoline, protoberberine, and 1-benzoylisoquinoline skeletons. Therefore, it is assumed that even in the plants it plays a key role in the formation and interconversion of the benzylisoquinoline alkaloids with 17 carbon atoms in the skeleton (Scheme 45). 

R = Me, CH2Ph) with tri-n-butyl tin hydride followed by NaBHjCN reduction affords the 7-exo cyclization products (165 R = Me, CHzPh), even if in only poor to moderate yield <9ITL2829>. In a similar reaction, 2,2-dichloro-iV-methyl-iV-(o-allylphenyl)-acetamide furnishes the 1-exo product, 4-methyl-2,3,4,5-tetrahydro-l/7-benz[Z)]azepine (166) in 49% yield <91JCS(P1)353>. The established photo-induced cyclization of chloracetamides has been applied to a synthesis of the azepino[3,4,5-c,ring system isomeric to that of the clavicipitic acids <88SC671>. 

The acid-catalyzed cyclization of Af -phenethyl-2-phenyl-2-hydroxyethylainines is an established method for the preparation of benz[d]azepines <84CHEC-l(7)49l>, but none of the methods permit the direct synthesis of chiral products. If, however, the starting material is converted into the chiral chromium tricarbonyl complex prior to cyclization, the ring closure proceeds in a stereospecific... 

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