Metal‐Free Reductive Coupling of <i>para</i>‐Quinone Methides with 4‐Cyanopyridines Enabled by Pyridine‐Boryl Radicals: Access to Pyridylated Diarylmethanes with Anti‐Cancer Activity
Chuan‐Hua Qu, Lixia Gao, Yan Tang, Yuan Liu, Xiao‐Qin Luo, Gui‐Ting Song
Abstract
Abstract Reported herein is a streamlined protocol to produce pyridylated diarylmethanes through pyridine‐boryl radical induced reductive coupling between para ‐quinone methides ( p ‐QMs) and 4‐cyanopyridines using bis(pinacolato)diboron (B 2 pin 2 ) as a templated reagent. The metal‐free process is characterized by an operationally simple approach, excellent chemoselectivity (1,2‐ vs. 1,6‐selectivity), and a broad substrate scope with good functional group compatibility. The mechanistic studies provided important insights into the reductive cross‐coupling process between diarylmethyl radical and pyridine‐boryl radical. Moreover, part of the obtained pyridylated diarylmethane products were screened against a panel of cancer cell lines, and 3 v was confirmed to significantly inhibit the proliferation of head and neck squamous cell carcinoma (HNSCC) cells. This method offers a platform for the preparation of new lead compounds with antitumor activity.