4.2 - Synthesis of Monocyclic Rings with One Heteroatom

Abstract

This chapter provides an overview of the main types of reactions used in synthesis of monocyclic rings with one heteroatom. For all the saturated monocyclic rings with one heteroatom, intramolecular nucleophilic displacement with the formation of C–Z bond(s) is an important preparative method. Other significant synthetic routes for the various ring sizes include: electrocyclic addition to double bonds for three-membered rings; [2+2] photocyclizations for four-membered rings; formation of one C–C bond for five- and six-membered rings; and ring expansion of carbocycles for six-membered and larger rings. Most monoheterocycles with one cyclic double bond are prepared by C–Z bond formation in which the Z atom acts as the nucleophile. However, for six-membered rings of this type, Diels–Alder reactions are especially important. Three-membered rings are also atypical: azirines are often made by C–N bond formation from precursors in which N is electrophilic or has nitrene character, while oxirenes are generally unstable and can only be generated as transient intermediates. Ring-closing metathesis (RCM) has emerged as one of the most significant methodologies applicable to the synthesis of a broad range of partially unsaturated heterocycles with five-membered and larger rings. The chapter further discusses the synthesis of three-, four-, five-, six-, and seven-membered monocyclic rings with one heteroatom, including those containing two endocyclic double bonds and those containing three endocyclic double bonds.