Synthesis of γ-Oxo-phosphonates via N-Heterocyclic Carbene-Catalyzed Acylphosphorylation of Alkenes.

In this study, we present an N-heterocyclic carbene-catalyzed method for the radical acylphosphorylation of alkenes. Electrochemical investigations were employed to identify an appropriate class of oxime phosphonates capable of undergoing a single-electron transfer (SET) with Breslow enolates. The resulting phosphoryl radicals were effectively coupled with diverse styrenes and aldehydes to yield a variety of γ-oxo-phosphonates. Both radical clock experiments and electrochemical studies support our reaction design, and a plausible mechanism for the organocatalytic transformation is proposed.

Synthesis of Pyrroloindolines via N-Heterocyclic Carbene Catalyzed Dearomative Amidoacylation of Indole Derivatives.

Pyrroloindoline is a privileged heterocyclic motif that is widely present in many natural products and pharmaceutical compounds. Herein, we report an amidyl radical-mediated dearomatization for synthesizing a series of pyrroloindolines via N-heterocyclic carbene catalysis. In this organocatalytic process, the Breslow enolate served as both a single electron donor and an acyl radical equivalent to assemble C3a-acyl pyrroloindolines with a broad substrate scope. Sequential reduction of the indole derivatives provided the analogues of (±)-desoxyeseroline, which exhibited potential anticancer activity.

Diastereoselective Radical Aminoacylation of Olefins through N-Heterocyclic Carbene Catalysis.

There have been significant advancements in radical-mediated reactions through covalent-based organocatalysis. Here, we present the generation of iminyl and amidyl radicals via N-heterocyclic carbene (NHC) catalysis, enabling diastereoselective aminoacylation of trisubstituted alkenes. Different from photoredox catalysis, single electron transfer from the deprotonated Breslow intermediate to O-aryl hydroxylamine generates an NHC-bound ketyl radical, which undergoes diastereocontrolled cross-coupling with the prochiral C-centered radical. This operationally simple method provides a straightforward access to a variety of pyrroline and oxazolidinone heterocycles with vicinal stereocenters (77 examples, up to >19:1 d.r.). Electrochemical studies of the acyl thiazolium salts support our reaction design and highlight the reducing ability of Breslow-type derivatives. A detailed computational analysis of this organocatalytic system suggests that radical-radical coupling is the rate-determining step, in which π-π stacking interaction between the radical intermediates subtly controls the diastereoselectivity.