in the absence of aryl iodides is consistent with
the Pd(II)/Pd(IV) pathway in which Pd(II) cleaves
the C–H bond first and subsequently undergoes
oxidative addition with an aryl iodide (26). We have
found that intermediate A reacts with iodobenzene
stoichiometrically to provide 2 (see supplementary
materials). However, the addition of TFA is required for this transformation, presumably to facilitate the dissociation of one of the pyridine ligands.
These intermediates are viable precatalysts for primary and secondary C(sp3)–H arylation, respectively (Fig. 6B). These rare and valuable C(sp3)–H
insertion intermediates provide a promising platform for further kinetic and computational study
of elementary steps in a well-defined manner.
References and Notes
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Acknowledgments: We gratefully acknowledge The Scripps
Research Institute, the NIH (National Institute of
General Medical Sciences, grant 2R01GM084019),
and Bristol-Myers Squibb for financial support. H.F. is
a visiting scholar sponsored by Sichuan University.
J.H. developed C(sp3)–H arylation and olefination and
conducted most of the experiments; S.L. synthesized
quinoline ligands; Y.D., H.F., B.N.L., and J.E.S. performed
large-scale reactions; A.H. obtained the crystal structures
shown in Fig. 6; and J.-Q. Y. directed the project. Metrical
parameters for the structures of 7f, intermediate A,
and intermediate B are available free of charge from
the Cambridge Crystallographic Data Centre under
reference numbers CCDC-985675, -985676, and
-985677, respectively. A provisional patent application
has been filed and is available under patent application
no. U.S. 61/946165.
Figs. S1 to S3
Tables S1 to S6
2 December 2013; accepted 19 February 2014
Fig. 6. Mechanistic studies. (A) Synthesis and crystallography of primary and secondary C(sp3)–H activation intermediates. Oak Ridge thermal
ellipsoid plots (30% probability ellipsoids) of intermediate A and intermediate B are shown. (B) Catalytic reactivity of intermediates in C(sp3)–H