Alkylnitrogen Compounds: Amines and Their Salts

Abstract

This chapter provides an overview of the synthesis of alkylamines chiefly covering the literature of the period 1995–2003. Representative methods for the introduction of nitrogen include electrophilic aminations (involving replacement of hydrogen by nitrogen), the direct N-monoalkylation of amines (usually of limited value for primary amines, though enhanced by Mitsunobu conditions), and the use of the phthaloyl group followed by cleavage (Gabriel synthesis). Amines, especially secondary amines, can be prepared from other amines by alkylation at nitrogen, and recent improvements are discussed, especially in regard to reductive aminations in general, and the Eschweiler–Clarke and Mannich reactions. Dealkylation of tertiary amines, especially using α-chloroethylchloroformate, is another useful route to amines. Methods of removal of a variety of N-protective groups are also described. Functional group interconversions are systematically discussed since they provide many important routes to amines, notable transformations including: amination of organometallic reagents, reductive aminations involving aldehydes or ketones, reduction of imines, addition of an organometallic reagent to CN bonds, conjugate addition of amines to electrophilic alkenes, conversion of azides into amines either by direct reduction or by the Staudinger reaction, reduction of nitro compounds and amides. Preparations of cyclic amines are discussed in detail for aziridines, azetidines, pyrrolidines, and piperidines. Notable advances in asymmetric syntheses, both stoichiometric and catalytic, are described throughout this chapter.