2,6-Bridged 3-benzazocines

Starting from the analogous TV-(2 -iodophenyl)-4-aminocyclohexanone derivative the bridged benzazocine, a framework present in several natural products, was isolated in near quantitative yield (4.7.),8... 

Streuff and coworkers have developed elegant and versatile cross-coupling reactions in the presence of a low-valent titanium catalyst for the synthesis of 1,6-difunctionalised ketonitriles, aminoketones and pyrrolidinones, a-hydrojyketones and a-aminoketones and bridged benzazocines and benzoxocines (Scheme 5.1). In general, the catalytic system is comprised of titanocene dichloride in the presence of zinc powder as reductant and gives good to excellent yields of the aforementioned products. 

A bridged benzazocine, the analgesic cyclazocine (142), with scarcely any structural relation with this group, showed reserpine and tetrabenazine antagonism [345,346]. There was clinical improvement in patients with depression in an open trial, but a narrow therapeutic range has been mentioned [347]. 

A series of unusual amidinium benzomorphans has been described by Strauss et a/.<53 55) where some members of the series exhibit narcotic antagonist properties. Their synthesis involves a meta bridging process of di- and trinitronaphthalenes (116) with a-phenyl N,N-dimethylacetamidine (117) to produce two isomeric benzazocine amidinium nitronates as their a-phenyl-N,N-dimethylacetamidinium salts (AmH+). The benzomorphan 118 is formed in ethanolic solution, whereas the isomeric benzazocine (119) results from reaction in dimethylsulfoxide. 

This chapter details the nomenclature, thermodynamics, reactions, and synthesis, and summarizes the experimental structural methods and applications in the following order (i) unsaturated, partially saturated, fully saturated monocyclic azocines, (ii) benzazocines, and (iii) dibenzazocines. The nitrogen bridged systems and unique compounds are not given detailed treatment owing to space limitations. 

---