title: Potassium tert-Butoxide-Catalyzed Dehydrogenative C-H Silylation of Heteroaromatics: A Combined Experimental and Computational Mechanistic Study.
abstract: 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]4as 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 H2gas. In situ NMR experiments with deuterated substrates show that H2is formed by a cross-dehydrogenative mechanism. The stereochemical course at the silicon center was investigated utilizing a2H-labeled silolane probe; complete scrambling at the silicon center was observed, consistent with a number of possible radical intermediates or hypercoordinate silicates.
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology , Pasadena, California 91125, United States.
authors.forename: Wen-Bo
authors.initials: WB
authors.lastname: Liu
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology , Pasadena, California 91125, United States.
authors.forename: David P
authors.initials: DP
authors.lastname: Schuman
authors.affiliation: Department of Chemistry and Biochemistry, University of California , Los Angeles, California 90095, United States.
authors.forename: Yun-Fang
authors.identifier: 0000-0002-6287-1640
authors.initials: YF
authors.lastname: Yang
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology , Pasadena, California 91125, United States.
authors.forename: Anton A
authors.initials: AA
authors.lastname: Toutov
authors.affiliation: Department of Chemistry and Biochemistry, University of California , Los Angeles, California 90095, United States.
authors.forename: Yong
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Institut für Chemie, Technische Universität Berlin , Strasse des 17. Juni 115, 10623 Berlin, Germany.
authors.forename: Hendrik F T
authors.identifier: 0000-0003-3748-6609
authors.initials: HFT
authors.lastname: Klare
authors.affiliation: Department of Chemistry, Florida Institute of Technology , 150 West University Boulevard, Melbourne, Florida 32901, United States.
authors.forename: Nasri
authors.initials: N
authors.lastname: Nesnas
authors.affiliation: Institut für Chemie, Technische Universität Berlin , Strasse des 17. Juni 115, 10623 Berlin, Germany.
authors.forename: Martin
authors.identifier: 0000-0002-1487-9218
authors.initials: M
authors.lastname: Oestreich
authors.affiliation: Department of Chemistry, The Scripps Research Institute , La Jolla, California 92037, United States.
authors.forename: Donna G
authors.identifier: 0000-0001-9829-8375
authors.initials: DG
authors.lastname: Blackmond
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology , Pasadena, California 91125, United States.
authors.forename: Scott C
authors.initials: SC
authors.lastname: Virgil
authors.affiliation: Department of Chemistry, Stanford University , Stanford, California 94305, United States.
authors.forename: Shibdas
authors.initials: S
authors.lastname: Banerjee
authors.affiliation: Department of Chemistry, Stanford University , Stanford, California 94305, United States.
authors.forename: Richard N
authors.identifier: 0000-0001-5266-4253
authors.initials: RN
authors.lastname: Zare
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology , Pasadena, California 91125, United States.
authors.forename: Robert H
authors.identifier: 0000-0002-0057-7817
authors.initials: RH
authors.lastname: Grubbs
authors.affiliation: Department of Chemistry and Biochemistry, University of California , Los Angeles, California 90095, United States.
authors.forename: K N
authors.identifier: 0000-0002-8387-5261
authors.initials: KN
authors.lastname: Houk
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology , Pasadena, California 91125, United States.
authors.forename: Brian M
authors.identifier: 0000-0001-9837-1528
authors.initials: BM
authors.lastname: Stoltz