Direct C–H Bond Imidation with Benzoyl Peroxide as a Mild Oxidant and a Reagent

Abstract

A simple and mild Cu-catalyzed oxidative three-component oxidative Ugi-type method for the synthesis of a variety of substituted imides has been developed. In this direct imidation approach, benzoyl peroxide serves as both the oxidant and the carboxylate source, allowing not only the functionalization of C­(sp3)–H bonds in α-position to an amine but also benzylic substrates. This procedure presents a wide substrate-type and functional group tolerance. Moreover, the mildness of the method permitted us to extend its application to the late stage functionalization of complex natural products such as the alkaloids brucine and strychnine, leading to interesting highly functionalized imide derivatives. On the basis of experimental and computational studies, a plausible mechanism has been proposed.

Visible-light photocatalytic metal-free multicomponent Ugi-like chemistry

“…By applying standard conditions as for the Ugi-3CR (Table 1, entry 2) a small library of imide derivatives (20)(21)(22)(23)(24)(25)Fig. 3) was obtained.…”

“…3) was obtained. The reaction proved to be suitable for different cyclic tertiary aromatic amines, such as N-phenyltetrahydroisoquinoline (20)(21)(22), N-phenylpyrrolidine (23 and 24, Fig. 3), and N-phenylpiperidine (25, Fig.…”

Electrochemical TEMPO-Catalyzed Oxidative Ugi-Type Reaction

“…To circumvent this problem, the concept of generating the adequate carbonyl/imine electrophiles by means of the in situ oxidation of the corresponding alcohol/amine emerged. , As the first milestone in oxidative IMCRs, Zhu et al succeeded in performing an alcohol-based 3-component Passerini reaction by employing 2-iodoxybenzoic acid (IBX) as the stoichiometric oxidant (Scheme , eq (a)) . Whereas a catalytic version of this multicomponent process was later reported, , more attention was subsequently paid to oxidative 3-component Ugi–Joullié-type IMCRs, in which an amine or an aniline derivative serves as the imine/iminium precursor (Scheme , eq (b)). − …”

The Breadth and Depth of C–H Functionalization

“…Here again, we see a wide range of different tactics. Several of the reported methods rely on oxygen present in air as the terminal oxidant, and others rely on stoichiometric metal oxidants such as Ag­(I) or Cu­(II), or main group reagents such as peroxides, , persulfates, , and bis­(trifluoroacetoxy)­iodo]­benzene . In some instances, direct oxidation of C–H bonds was accomplished such as through the use of different types of aminating, halogenating, or sulfur reagents.…”

“…A variety of functionality was installed even when the same carbon–atom connectivity was produced. For example, for C–C bond formation, C­(sp 2 )–H and C­(sp 3 )–H bonds were activated to provide C­(sp 2 )–C­(sp 2 ), C­(sp 2 )–C­(sp 3 ), and C­(sp 3 )–C­(sp 2 ) bonds, and the introduction of aromatic, heteroaromatic, alkenyl, , allyl, , benzyl, alkyl, , trifluoromethyl, perdeuteromethyl, and carboximide functionality were each described in one or more of the contributing articles. Both C­(sp 2 )–H and C­(sp 3 )–H bond activation to form C–N bonds were also reported, and both intermolecular and intramolecular approaches were used to install diverse nitrogen functionality such as amines protected as carbamates and sulfonamides, , nitrogen heterocycles, and even the nitro group …”