ORGANIC
LETTERS
XXXX
Vol. XX, No. XX
000–000
Palladium-Catalyzed Arylation of Simple
Arenes with Iodonium Salts
Thomas E. Storr and Michael F. Greaney*
School of Chemistry, University of Manchester, Oxford Road, Manchester,
M13 9PL, U.K.
Received February 12, 2013
ABSTRACT
The development of an arylation protocol for simple arenes with diaryliodonium salts using the HerrmannꢀBeller palladacycle catalyst is
reported. The reaction takes simple aromatic feedstocks and creates valuable biaryls for use in all sectors of the chemical industry.
Biaryls are important motifs in pharmaceuticals, agro-
chemicals, and natural products.1 Their construction using
transition metal (TM) mediated coupling has become
a major research area in synthesis,2 with a rich heritage
dating back over a century to reactions such as the Pschorr
cyclization3 and Ullmann coupling.4 The importance of
biaryl synthesis drives continual efforts at improving reac-
tion efficiency and atom economy, with the area of CꢀH
arylation representing a significant recent development
toward these two goals.5 Harnessing unfunctionalized
CꢀH components as reactants for biaryl synthesis avoids
multistep syntheses of activated precursors, enhancing effi-
ciency and opening up new substrate classes for value-added
synthesis.
Recent work has identified aryliodanes and aryliodo-
nium salts as powerful reagents for CꢀH arylation, offer-
ing new reaction pathways and conditions relative to their
aryl halide congeners.6 Their enhanced reactivity, includ-
ing the facility to access higher oxidation states of TM
catalysts (e.g., Pd and Cu), has enabled a variety of CꢀH
bond arylations on otherwise intractable substrates.7 We
were interested in using these compounds to develop a
CꢀH arylation system for simple arene feedstocks.
(6) For reviews and books on iodine(III) reagents, see: (a) Wirth, T.
Hypervalent Iodine Chemistry: Modern Developments in Organic Synthe-
sis; Topics in Current Chemistry; Springer-Verlag: Heidelberg, 2010.
(b) Merritt, E. A.; Olofsson, B. Angew. Chem., Int. Ed. 2009, 48, 9052.
(c) Zhdankin, V. V.; Stang, P. J. Chem. Rev. 2008, 108, 5299. (d) Deprez,
N. R.; Sanford, M. S. Inorg. Chem. 2007, 46, 1924.
(7) Selected examples: (a) Daugulis, O.; Zaitsev, V. G. Angew.
Chem., Int. Ed. 2005, 44, 4046. (b) Kalyani, D.; Deprez, N. R.; Desai,
L. V.; Sanford, M. S. J. Am. Chem. Soc. 2005, 127, 7330. (c) Deprez,
N. R.; Kalyani, D.; Krause, A.; Sanford, M. S. J. Am. Chem. Soc. 2006,
128, 4972. (d) Deprez, N. R.; Sanford, M. S. J. Am. Chem. Soc. 2009,
131, 11234. (e) Phipps, R. J.; Gaunt, M. J. Science 2009, 323, 1593. (f)
Bedford, R. B.; Mitchell, C. J.; Webster, R. L. Chem. Commun. 2010, 46,
3095. (g) Xiao, B.; Fu, Y.; Xu, J.; Gong, T.-J.; Dai, J.-J.; Yi, J.; Liu, L.
J. Am. Chem. Soc. 2010, 132, 468. (h) Lopez-Suarez, L.; Greaney, M. F.
Chem. Commun. 2010, 47, 7992. (i) Huang, C.; Chernyak, N.; Dudnik,
A. S.; Gevorgyan, V. Adv. Synth. Catal. 2011, 353, 1285. (j) Ciana, C.-L.;
Phipps, R. J.; Brandt, J. R.; Meyer, F.-M.; Gaunt, M. J. Angew. Chem.,
Int. Ed. 2011, 50, 458. (k) Ackermann, L.; Dell’Acqua, M.; Fenner, S.;
Vicente, R.; Sandmann, R. Org. Lett. 2011, 13, 2358. (l) Wen, J.; Zhang,
R.-Y.; Chen, S.-Y.; Zhang, J.; Yu, X.-Q. J. Org. Chem. 2012, 77, 766. (m)
Liu, Y.-X.; Xue, D.; Wang, J.-D.; Zhao, C.-J.; Zou, Q.-Z.; Wang, C.;
Xiao, J. Synlett 2013, 507.
(1) (a) Kozlowski, M. C.; Morgan, B. J.; Linton, E. C. Chem. Soc.
Rev. 2009, 38, 3193. (b) Bringmann, G.; Gunther, C.; Ochse, M.;
Schupp, O.; Tasler, S. Prog. Chem. Org. Nat. Prod. 2001, 82, 1. (c)
Hajduk, P. J.; Bures, M.; Praestgaard, J.; Fesik, S. W. J. Med. Chem.
2000, 43, 3443. (d) Mason, J. S.; Morize, I.; Menard, P. R.; Cheney,
D. L.; Hulme, C.; Labaudiniere, R. F. J. Med. Chem. 1999, 42, 3251.
(2) (a) Cepanec, I. Synthesis of Biaryls; Elsevier Ltd.: Oxford, 2004. (b)
de Meijere, A.; Diederich, F. Metal Catalyzed Cross-Coupling Reactions,
2nd ed.; Wiley-VCH: Weinheim, 2004. (c) Hassan, J.; Sevignon, M.; Gozzi,
C.; Schulz, E.; Lemaire, M. Chem. Rev. 2002, 102, 1359.
(3) Pschorr, R. Chem. Ber. 1896, 29, 496.
(4) Ullmann, F.; Bielecki, J. Chem. Ber. 1901, 34, 2174.
(5) (a) Yu, J.-Q.; Shi, Z.-J. Top. Curr. Chem.: C-H Activation,
Springer, Heidelberg, 2010, Vol. 292. (b) Ackermann, L. Modern Arylation
Methods, Wiley-VCH, Weinheim, 2009. (c) Alberico, D.; Scott, M. E.;
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10.1021/ol400412z
XXXX American Chemical Society