Transition metal-free direct dehydrogenative arylation of activated C(sp3)-H bonds: synthetic ambit and DFT reactivity predictions
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Updated: Feb 2, 2026

A Microwave-Assisted Direct Heteroarylation of Ketones Using Transition Metal Catalysis
Published on: February 16, 2020
Kaitlyn Lovato1, Lirong Guo2, Qing-Long Xu3
1Department of Chemistry , Rice University , BioScience Research Collaborative , Houston , Texas 77005 , USA .
Abstract:
A transition metal-free dehydrogenative method for the direct mono-arylation of a wide range of activated C(sp3)-H bonds has been developed. This operationally simple and environmentally friendly aerobic arylation uses tert-BuOK as the base and nitroarenes as electrophiles to prepare up to gram quantities of structurally diverse sets (>60 examples) of α-arylated esters, amides, nitriles, sulfones and triaryl methanes. DFT calculations provided a predictive model, which states that substrates containing a C(sp3)-H bond with a sufficiently low pK a value should readily undergo arylation. The DFT prediction was confirmed through experimental testing of nearly a dozen substrates containing activated C(sp3)-H bonds. This arylation method was also used in a one-pot protocol to synthesize over twenty compounds containing all-carbon quaternary centers.
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