Direct α-Alkenylation of Cyclic Amines with Maleimides through Fe(III)-Catalyzed C(sp³)–H/C(sp²)–H Cross Dehydrogenative Coupling

Abstract

Presented herein is a novel and efficient α-C(sp 3 )− H alkenylation of cyclic amines with maleimides. Mechanistically, this C(sp 3 )−H/C(sp 2 )−H cross dehydrogenative coupling (CDC) reaction involves a cascade procedure including oxidative α-amino radical formation from the cyclic amine substrate and nucleophilic addition of the in situ formed α-amino radical onto the electrondeficient carbon−carbon double bond of maleimide followed by oxidation and β-elimination. Notably, this direct α-functionalization provides an effective alternative to the conventional ionic reaction mode, in which an imine or iminium intermediate is formed to react with electron-rich coupling partners other than electron-deficient ones. In general, this method features readily available and structurally diverse substrates, a green and economical catalyst, a unique reaction pathway, mild reaction conditions, high efficiency, and excellent atom economy. This new reaction enriches the application of Fe(III)-catalyzed C(sp 3 )−H activation and functionalization.

An Electrocatalytic Strategy for Dehydrogenative [4 + 2] Cycloaddition over a Cobalt‐Based Catalyst

“…To gain further insights into the reaction mechanism of this transformation, we carried out a set of control experiments (Scheme 1). The reaction was completely inhibited when we performed the standard reaction with 2,2,6,6‐tetramethyl‐1‐piperidinyloxy (TEMPO) or butylated hydroxytoluene (BHT) as the radical scavengers, [ 28 ] respectively. In the TEMPO experiment, radical trapping product N ,4‐dimethyl‐ N ‐(((2,2,6,6‐tetramethylpiperidin‐ 1‐yl)oxy)methyl)aniline ( 3o ) was detected by GC‐MS (Figure S10).…”

The Recent Advances in Iron‐Catalyzed C(sp3)−H Functionalization

“…In 2021, Xuesen Fan et al reported the first eco-friendly cascade protocol for α-alkenylation of cyclic amines 87 through cross dehydrogenative coupling (CDC) with maleimide 88 via single electron transfer (SET) using an iron catalyst in the presence of DCP afforded product 89 (Scheme 20). [52] This protocol is highly desirable for α-alkenylation of various cyclic amines afforded a wide range of pharmaceutically active scaffolds. which exhibits various biological activities such as antimalarial, anesthetic, CNS-stimulation, antianginal, and antipsychotic.…”

One-Pot Three-Component Coupling Reaction of α-Amino Aryl Ketones, Indoles, and Perbromomethane Under Mild Conditions

“…From the perspective of simplicity, the oxidative cross-dehydrogenation coupling reaction has become a very good tool for constructing complex molecules through simple reaction materials (Li., 2009;Scheuermann., 2010;Yeung and Dong., 2011;Girard et al, 2014;Song et al, 2017;Wang et al, 2021). Easy-to-prepare and cheap α-amino carbonyl units are widely present in many natural products and drug molecules (Ohfune., 1992).…”