Organic Letters
Letter
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(I)−aryl complex F, which can undergo transmetalation with
additional boronic acid starting material to regenerate
intermediate B.24
Notably, it is hypothesized that the rhodium(III) acyl
intermediate D contains two aryl groups. This species can
undergo reductive elimination to generate a biaryl byproduct,
the starting material, or the desired product. Substrate-specific
electron or steric effects presumably dictate the selectivity of
the reductive elimination pathway, as only traces of biaryl
species are observed in the reaction. As there are no clearly
irreversible steps within the catalytic cycle, it is hypothesized
that the extent of product formation is largely driven by the
excess of boronic acid and the relative stability of the boronic
acids and quinolinyl ketone. Work is underway to further
elucidate trends in substrates to promote a broader scope of
productive reductive elimination and product formation.
In summary, we have developed a method that efficiently
cross-couples both alkyl and aryl substituted quinolinyl ketones
with boronic acids. The reaction is tolerant of a variety of
electron-deficient aryl boron reagents, which overcomes current
limitations in C−C bond activation and functionalization
methodologies. The reaction proceeds without the use of
oxidants and in a catalytic fashion. Finally, the use of methyl
boronic acid as a cross-coupling agent provides evidence for the
feasibility of installing sp3 functionality at ketones.
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ASSOCIATED CONTENT
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S
* Supporting Information
(17) For recent, notable examples, see: (a) Wan, L.; Dastbaravardeh,
N.; Li, G.; Yu, J.-Q. J. Am. Chem. Soc. 2013, 135, 18056. (b) Li, J.;
Burke, M. D. J. Am. Chem. Soc. 2011, 133, 13774. (c) Gao, F.; Carr, J.
L.; Hoveyda, A. H. J. Am. Chem. Soc. 2014, 136, 2149.
(18) Wang, J.; Chen, W.; Zuo, S.; Liu, L.; Zhang, Z.; Wang, J. Angew.
Chem., Int. Ed. 2012, 51, 12334.
The Supporting Information is available free of charge on the
Experimental data, optimization data, characterization
information, and spectra (PDF)
(19) Bour, J. R.; Green, J. C.; Winton, V. J.; Johnson, J. B. J. Org.
Chem. 2013, 78, 1665.
(20) The presence of an ortho-fluorine has been calculated to stabilize
a Rh−Ar complex by 5.5 kcal/mol. See: Clot, E.; Eisenstein, O.; Jasim,
N.; MacGregor, S. A.; McGrady, J. E.; Perutz, R. N. Acc. Chem. Res.
2011, 44, 333.
(21) It should be noted that Suzuki-like coupling was observed for a
number of boronic acid substrates, precluding the general use of the
ortho-fluorinated quinolinyl ketone.
(22) Results from the optimization process can be found in the
(23) See ref 18. Quinolinyl ketone (0.05 mmol), boronic acid (0.125
mmol), CuI (0.1 mmol), K2CO3 (0.1 mmol), and Rh(PPh3)3Cl (10
mol %) in xylene (0.5 mL) at 130 °C under air.
AUTHOR INFORMATION
Corresponding Author
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Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
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The authors thank the NSF (CHE-1148719) and the Henry
Dreyfus Teacher-Scholar Award Program (TH-15-030) for
funding. J.B.J. acknowledges support from the Hope College
Schaap Scholars Program. We also gratefully acknowledge
funding for instrumentation from the NSF (CHE-0922623).
(24) (a) Li, Y.-G.; He, G.; Qin, H.-L.; Kantchev, E. A. B. Dalton
Trans. 2015, 44, 2737. (b) Dauth, A.; Love, J. A. Angew. Chem., Int. Ed.
2010, 49, 9219. (c) Zhao, P.; Incarvito, C.; Hartwig, J. F. J. Am. Chem.
Soc. 2007, 129, 1876.
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