Seven-Membered Rings

This chapter describes the chemistry of seven-membered heterocycles, with emphasis on research focussing on the construction and reactions of these heterocyclic systems. A continued trend has been to use seven-membered heterocyclic motifs in derivatives of biologically active molecules, and a summary of the key advancements in pharmacological activity of these derivatives is reviewed in the chapter. The chiral azepine are synthesized from phenylalanine by way of the alkenyl amine derivative that underwgoes oxidative cleavage and intramolecular reductive amination. Reductive amination is the method used for the formation of the azepine as a derivative of deoxynorjirimycin. Constrained phenylalanine derivatives are synthesised via an ene-yne metathesis that not only forms the azepine ring but gives a diene that is transformed into the fused benzoazepine. Azepines and heterocyclic fused derivatives are formed in good to moderate yields by the reaction of an enamine.