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Silylation of C–H bonds in aromatic heterocycles by an Earth-abundant metal catalyst

Toutov, Anton A. and Liu, Wen-Bo and Betz, Kerry N. and Fedorov, Alexey and Stoltz, Brian M. and Grubbs, Robert H. (2015) Silylation of C–H bonds in aromatic heterocycles by an Earth-abundant metal catalyst. Nature, 518 (7537). pp. 80-84. ISSN 0028-0836. http://resolver.caltech.edu/CaltechAUTHORS:20141118-102135823

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Abstract

Heteroaromatic compounds containing carbon–silicon (C–Si) bonds are of great interest in the fields of organic electronics and photonics1, drug discovery, nuclear medicine and complex molecule synthesis, because these compounds have very useful physicochemical properties. Many of the methods now used to construct heteroaromatic C–Si bonds involve stoichiometric reactions between heteroaryl organometallic species and silicon electrophiles or direct, transition-metal-catalysed intermolecular carbon–hydrogen (C–H) silylation using rhodium or iridium complexes in the presence of excess hydrogen acceptors. Both approaches are useful, but their limitations include functional group incompatibility, narrow scope of application, high cost and low availability of the catalysts, and unproven scalability. For this reason, a new and general catalytic approach to heteroaromatic C–Si bond construction that avoids such limitations is highly desirable. Here we report an example of cross-dehydrogenative heteroaromatic C–H functionalization catalysed by an Earth-abundant alkali metal species. We found that readily available and inexpensive potassium tert-butoxide catalyses the direct silylation of aromatic heterocycles with hydrosilanes, furnishing heteroarylsilanes in a single step. The silylation proceeds under mild conditions, in the absence of hydrogen acceptors, ligands or additives, and is scalable to greater than 100 grams under optionally solvent-free conditions. Substrate classes that are difficult to activate with precious metal catalysts are silylated in good yield and with excellent regioselectivity. The derived heteroarylsilane products readily engage in versatile transformations enabling new synthetic strategies for heteroaromatic elaboration, and are useful in their own right in pharmaceutical and materials science applications.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1038/nature14126DOIArticle
http://www.nature.com/nature/journal/v518/n7537/full/nature14126.htmlPublisherArticle
http://rdcu.be/cmm5PublisherFree ReadCube access
ORCID:
AuthorORCID
Toutov, Anton A.0000-0002-6561-0462
Fedorov, Alexey0000-0001-9814-6726
Stoltz, Brian M.0000-0001-9837-1528
Grubbs, Robert H.0000-0002-0057-7817
Additional Information:© 2015 Macmillan Publishers. These authors contributed equally to this work. Received 15 August; accepted 27 November 2014. This work was supported by the NSF under the CCI Center for Selective C–H Functionalization(CHE-1205646) and under CHE-1212767, and by BP under the XC^2 initiative. We thank the Novartis Institutes for Biomedical Research Incorporated for the donation of samples to the CCHF. D. Morton is thanked for a donation of thenalidine. A.A.T. is grateful to the Resnick Sustainability Institute at Caltech and to Dow Chemical for a predoctoral fellowship, and to NSERC for a PGS D fellowship. The Shanghai Institute of Organic Chemistry (SIOC) and S.-L. You are thanked for a postdoctoral fellowship to W.-B.L. We thank S. Virgil and the Caltech Center for Catalysis and Chemical Synthesis for access to analytical equipment. D.Vandervelde is acknowledged for assistance with NMR interpretation. N. Dalleska is thanked for assistance with ICP-MS trace metal analysis. M. Shahgoli and N. Torian are acknowledged for assistance with high-resolution mass spectrometry. A.A.T., W.-B.L. and K.N.B. developed the reactions, performed the experiments and analysed data. A.F. analysed data. A.A.T and R.H.G. had the idea for and directed the investigations with W.-B.L. and B.M.S. A.A.T. and W.-B.L. prepared the manuscript with contributions from all authors. All authors contributed to discussions.
Group:Resnick Sustainability Institute
Funders:
Funding AgencyGrant Number
NSFCHE-1205646
NSFCHE-1212767
BP XC2 Program UNSPECIFIED
Resnick Sustainability InstituteUNSPECIFIED
Dow Chemical CompanyUNSPECIFIED
Natural Sciences and Engineering Research Council of Canada (NSERC)UNSPECIFIED
Shanghai Institute of Organic Chemistry (SIOC)UNSPECIFIED
Record Number:CaltechAUTHORS:20141118-102135823
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20141118-102135823
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:51898
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:04 Feb 2015 18:28
Last Modified:11 Feb 2017 21:45

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