The Castagnoli–Cushman Reaction

Abstract

Since the first reports of the reaction of imines and cyclic anhydrides by Castagnoli and Cushman, this procedure has been applied to the synthesis of a variety of lactams, some of them with important synthetic or biological interest. The scope of the reaction has been extended to the use of various Schiff bases and anhydrides as well as to different types of precursors for these reagents. In recent years, important advances have been made in understanding the mechanism of the reaction, which has historically been quite controversial. This has helped to develop reaction conditions that lead to pure diastereomers and even homochiral products. In addition, these mechanistic studies have also led to the development of new multicomponent versions of the Castagnoli–Cushman reaction that allow products with more diverse and complex molecular structures to be easily obtained.

Imines with rare α-heteroatom substituted amine components generated in situ via the Staudinger/aza-Wittig tandem reaction and their application in multicomponent reactions

“…11 In this work, we aimed at extending the pool of azides involved in the Staudinger/aza-Wittig tandem reaction to obtain imines whose alternative synthesis would include the use of scarcely available or unstable amines (such as α-heteroatom substituted ones) as precursors. We investigated the reactivity and synthetic potential of these newly obtained types of imines by introducing them into medicinally important MCRs, namely the Staudinger synthesis, 13 the Castagnoli-Cushman reaction, 14 and the Ugi and azido-Ugi reactions. 3 One of the moieties ( phthalimide) introduced via the azide component was shown to be cleavable, which allowed the preparation of N-aminomethyl lactams.…”