Transition metal-free direct dehydrogenative arylation of activated C(sp3)–H bonds: synthetic ambit and DFT reactivity predictions

Kaitlyn Lovato; Lirong Guo; Qing-Long Xu; Fengting Liu; Muhammed Yousufuddin; Daniel H. Ess; László Kürti; Hongyin Gao

doi:10.1039/C8SC02758G

Transition metal-free direct dehydrogenative arylation of activated C(sp³)–H bonds: synthetic ambit and DFT reactivity predictions†

Kaitlyn Lovato,

^b Lirong Guo,^a Qing-Long Xu,

^c Fengting Liu,^a Muhammed Yousufuddin,^d Daniel H. Ess,*^e László Kürti

*^b and Hongyin Gao

*^a

Author affiliations

* Corresponding authors

^a Ministry of Education Key Laboratory of Colloid and Interface Chemistry, School of Chemistry and Chemical Engineering, Shandong University, Ji'nan 250100, China
E-mail: hygao@sdu.edu.cn

^b Department of Chemistry, Rice University, BioScience Research Collaborative, Houston, Texas, USA
E-mail: kurti.laszlo@rice.edu

^c Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing 210009, China

^d Life and Health Sciences Department, The University of North Texas at Dallas, Dallas, Texas 76016, USA

^e Department of Chemistry and Biochemistry, Brigham Young University, Provo, Utah 84602, USA
E-mail: dhe@chem.byu.edu

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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DOI: https://doi.org/10.1039/C8SC02758G
Article type: Edge Article
Submitted: 22 Jun 2018
Accepted: 23 Aug 2018
First published: 27 Aug 2018
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry

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Chem. Sci., 2018,9, 7992-7999

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Transition metal-free direct dehydrogenative arylation of activated C(sp³)–H bonds: synthetic ambit and DFT reactivity predictions

K. Lovato, L. Guo, Q. Xu, F. Liu, M. Yousufuddin, D. H. Ess, L. Kürti and H. Gao, Chem. Sci., 2018, 9, 7992 DOI: 10.1039/C8SC02758G

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Transition metal-free direct dehydrogenative arylation of activated C(sp³)–H bonds: synthetic ambit and DFT reactivity predictions†

Abstract

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Transition metal-free direct dehydrogenative arylation of activated C(sp³)–H bonds: synthetic ambit and DFT reactivity predictions

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