Modular Synthesis of Benzoylpyridines Exploiting a Reductive Arylation Strategy

Abstract

Herein we disclose a telescoped flow strategy to access electronically differentiated bisaryl ketones as potentially new and tunable photosensitizers containing both electron-rich benzene systems and electron-deficient pyridyl moieties. Our approach merges a light-driven (365 nm) and catalyst-free reductive arylation between aromatic aldehydes and cyanopyridines with a subsequent oxidation process. The addition of electrondonating and withdrawing substituents on the scaffold allowed effective modification of the absorbance of these compounds in the UV−vis region, while the continuous flow process affords high yields, short residence time, and high throughput.

Continuous Flow Approach for Benzylic Photo-oxidations Using Compressed Air

“…When performed in batch, some direct photooxidation of benzylic C–H bonds using anthraquinones required relatively long reaction times up to 24 h . Based on the prevalence of flow-based oxidation reactions with contributions from our group and others, we wished to address this issue, and set out to develop a readily scalable continuous photooxidation process for benzylic substrates under aerobic conditions using compressed air. SAS was thereby chosen as the photocatalyst due to its water-solubility, which allows the use of water as a green cosolvent as well as simple removal of the catalyst during extractive workup.…”

Visible-light-induced catalyst-free reductive coupling of aldehydes, ketones and imines with cyanopyridines

“…9 In the course of preparing this paper, Baumann and co-workers reported a UV lightinduced cross-coupling of aldehydes with cyanopyridines, utilizing N,N-diisopropylethylamine as the reductive reagent. 10 However, the reported substrate scope was limited to aldehydes. Building upon our prior investigations into transition-metal and photosensitizerfree photoreactions, 11 presented herein is a reductive arylation that employs visible light as the energy source and Hantzsch esters as the reductant, successfully facilitating the reductive arylation of aldehydes, ketones and imines with cyanopyridines (Scheme 1d).…”