Chapter 27 New Methods in Heterocyclic Chemistry

Abstract

This chapter discusses the introduction and modification of substituent groups, new methods for ring annelation, and synthetically useful ring transformation reactions; the three areas of heterocyclic chemistry. Numerous new methods for the introduction and modification of substituents continue to appear, reflecting the fact that this area of heterocyclic chemistry contains many of its greatest synthetic challenges. The introduction of substituent groups into protonated heterocyclic bases by free radicals, pioneered by Minisci and well reviewed over the past few years continues to be actively explored; further studies on alkylations, acylations, and carboethoxylations have been reported. Various substituents are readily displaced by an ipso substitution process from the 2-position of benzothiazole by the nucleophilic 1-adamantyl and acetyl radicals. The extension of these substituent group interchange processes to other heterocyclic systems could be of considerable synthetic utility. A general procedure for the introduction of substituents in heterocycles is the displacement of a good leaving group by an appropriate nucleophile. The most reactive substituent toward the displacement by nucleophiles appears to be methylsulfonyl. A versatile procedure for the introduction of alkyl, alkenyl, and epoxyalkyl groups into heterocycles, followed by appropriate manipulation of the resulting ylides, has been applied to the synthesis of various 6-substituted purines designed as inhibitors of adenylsuccinate synthetase and lyase. The chapter also discusses many recent developments in synthetic methodology in heterocyclic chemistry have dealt with new methods for annelation of a heterocyclic ring unto a pre-existing ring system. Many useful syntheses involve the deliberate transformation of one heterocyclic system into another by ring contraction, ring expansion, or ring transformation reaction.