A Caltech Library Service

Potassium tert-Butoxide-Catalyzed Dehydrogenative C–H Silylation of Heteroaromatics: A Combined Experimental and Computational Mechanistic Study

Liu, Wen-Bo and Schuman, David P. and Yang, Yun-Fang and Toutov, Anton A. and Liang, Yong and Klare, Hendrik F. T. and Nesnas, Nasri and Oestreich, Martin and Blackmond, Donna G. and Virgil, Scott C. and Banerjee, Shibdas and Zare, Richard N. and Grubbs, Robert H. and Houk, K. N. and Stoltz, Brian M. (2017) Potassium tert-Butoxide-Catalyzed Dehydrogenative C–H Silylation of Heteroaromatics: A Combined Experimental and Computational Mechanistic Study. Journal of the American Chemical Society, 139 (20). pp. 6867-6879. ISSN 0002-7863. doi:10.1021/jacs.6b13031.

[img] PDF - Accepted Version
See Usage Policy.

[img] PDF (Full experimental procedures, FTIR spectra, characterization data, and Cartesian coordinates of computational structures) - Supplemental Material
See Usage Policy.


Use this Persistent URL to link to this item:


We recently reported a new method for the direct dehydrogenative C–H silylation of heteroaromatics utilizing Earth-abundant potassium tert-butoxide. Herein we report a systematic experimental and computational mechanistic investigation of this transformation. Our experimental results are consistent with a radical chain mechanism. A trialkylsilyl radical may be initially generated by homolytic cleavage of a weakened Si–H bond of a hypercoordinated silicon species as detected by IR, or by traces of oxygen which can generate a reactive peroxide by reaction with (KOt-Bu)_4 as indicated by density functional theory (DFT) calculations. Radical clock and kinetic isotope experiments support a mechanism in which the C–Si bond is formed through silyl radical addition to the heterocycle followed by subsequent β-hydrogen scission. DFT calculations reveal a reasonable energy profile for a radical mechanism and support the experimentally observed regioselectivity. The silylation reaction is shown to be reversible, with an equilibrium favoring products due to the generation of H_2 gas. In situ NMR experiments with deuterated substrates show that H_2 is formed by a cross-dehydrogenative mechanism. The stereochemical course at the silicon center was investigated utilizing a ^2H-labeled silolane probe; complete scrambling at the silicon center was observed, consistent with a number of possible radical intermediates or hypercoordinate silicates.

Item Type:Article
Related URLs:
URLURL TypeDescription Information
Liu, Wen-Bo0000-0003-2687-557X
Yang, Yun-Fang0000-0002-6287-1640
Toutov, Anton A.0000-0002-6561-0462
Liang, Yong0000-0002-7225-7062
Klare, Hendrik F. T.0000-0003-3748-6609
Nesnas, Nasri0000-0003-3511-940X
Oestreich, Martin0000-0002-1487-9218
Blackmond, Donna G.0000-0001-9829-8375
Virgil, Scott C.0000-0001-8586-5641
Banerjee, Shibdas0000-0002-3424-8157
Zare, Richard N.0000-0001-5266-4253
Grubbs, Robert H.0000-0002-0057-7817
Houk, K. N.0000-0002-8387-5261
Stoltz, Brian M.0000-0001-9837-1528
Alternate Title:KOt-Bu-Catalyzed Dehydrogenative C–H Silylation of Heteroaromatics: A Combined Experimental and Computational Mechanistic Study
Additional Information:© 2017 American Chemical Society. Received 19 December 2016. Published online 12 April 2017. The authors wish to thank the NSF under the CCI Center for Selective C–H Functionalization (CCHF) (CHE-1205646), CHE- 1212767 for support, the Novartis Institutes for Biomedical Research Incorporated for the donation of samples to the CCHF, and CHE-1361104. Calculations were performed on the Hoffman2 cluster at UCLA and the Extreme Science and Engineering Discovery Environment (XSEDE), which is supported by the NSF. The Shanghai Institute of Organic Chemistry (SIOC) and S.-L. You are thanked for a postdoctoral fellowship to W.-B.L. D.P.S. thanks the CCI Center for Selective C–H Functionalization for support and the Blackmond group (TSRI) for their assistance and hospitality. A.A.T. is grateful to Bristol-Myers Squibb, the Resnick Sustainability Institute at Caltech, and to Dow Chemical for predoctoral fellowship as well as to NSERC for a PGS D fellowship. M.O. is indebted to the Einstein Foundation (Berlin) for an endowed professorship. N.N. thanks Florida Tech for sabbatical leave and thanks B.M.S. and Caltech for hosting him in their research labs. We thank J. Buss (Caltech), N. Thompson (Caltech), Prof. Krenske (University of Queensland), and Prof. Jenkins (Griffith Univ.) for helpful discussions. The Peters, Bercaw, and Agapie groups (Caltech) are thanked for instrumentation. We thank Dr. Angelo Di Bilio for assistance in recording EPR spectra, Dr. Dave VanderVelde for NMR expertise, and Dr. Mona Shahgholi and Dr. Naseem Torian for mass spectrometry assistance (Caltech). We thank Claude Y. Legault for CYLView, used for the molecular graphics. The authors declare no competing financial interest.
Group:Resnick Sustainability Institute
Funding AgencyGrant Number
Shangai Institute of Organic ChemistryUNSPECIFIED
Bristol-Myers SquibbUNSPECIFIED
Resnick Sustainability InstituteUNSPECIFIED
Natural Sciences and Engineering Research Council of Canada (NSERC)UNSPECIFIED
Einstein Foundation BerlinUNSPECIFIED
Issue or Number:20
Record Number:CaltechAUTHORS:20170413-121146154
Persistent URL:
Official Citation:Potassium tert-Butoxide-Catalyzed Dehydrogenative C–H Silylation of Heteroaromatics: A Combined Experimental and Computational Mechanistic Study Wen-Bo Liu, David P. Schuman, Yun-Fang Yang, Anton A. Toutov, Yong Liang, Hendrik F. T. Klare, Nasri Nesnas, Martin Oestreich, Donna G. Blackmond, Scott C. Virgil, Shibdas Banerjee, Richard N. Zare, Robert H. Grubbs, K. N. Houk, and Brian M. Stoltz Journal of the American Chemical Society 2017 139 (20), 6867-6879 DOI: 10.1021/jacs.6b13031
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:76553
Deposited By: Ruth Sustaita
Deposited On:13 Apr 2017 22:15
Last Modified:15 Nov 2021 17:00

Repository Staff Only: item control page