Solid-phase synthesis of aryl, heteroaryl, and sterically hindered alkyl amines using the Curtius rearrangement

An efficient method for the solid-phase synthesis of aryl amines, heteroaryl amines, and sterically hindered alkyl amines has been developed. The key step in this process was the formation Of resin-bound carbamates (B) by the Curtius rearrangement of aryl carboxylic acids with Wang resin providing the trapping hydroxyl group. N-Alkylation reactions of B gave secondary amines in good yield. Some biaryl amines, which are found widely in biologically active Substances, were also prepared by the Suzuki reaction of resin-bound carbamates of 2-iodoaniline (16) or 3-(4,4.5,5-tetramethyl-1,3,2-dioxaborolaln-2-yl)aniline (21). The developed methods can be applied to the preparation of libraries containing aryl, heteroaryl, and sterically hindered alkyl amine structures as the pharmacophores. (c) 2008 Elsevier Ltd. All rights reserved.