ORGANIC
LETTERS
2011
Vol. 13, No. 18
4974–4976
An Improved Palladium-Catalyzed
Conversion of Aryl and Vinyl Triflates to
Bromides and Chlorides
Jun Pan, Xinyan Wang, Yong Zhang, and Stephen L. Buchwald*
Department of Chemistry, Massachusetts Institute of Technology, Cambridge,
Massachusetts 02139, United States
Received August 2, 2011
ABSTRACT
A facile Pd-catalyzed conversion of aryl and vinyl triflates to aryl and vinyl halides (bromides and chlorides) is described. This method allows
convenient access to a variety of aryl, heteroaryl, and vinyl halides in good to excellent yields and with greatly simplified conditions relative to our
previous report.
Aryl halides are present in a wide variety of biologically
active molecules.1 They are also important synthetic inter-
mediates that are used for numerous transformations.2
Traditional methods for producing aryl bromides and
chlorides from phenols require either forcing reaction
conditions3 or multistep sequences.4 Consequently, the
development of general and efficient methods for the
synthesis of aryl halides is of great importance. Aryl
triflates, which serve as alternatives to aryl halides in many
cross-coupling reactions,5 are often referred to as pseudo-
halides. However, unlike aryl halides, aryl triflates cannot
be used as precursors for the generation of free radicals6 or
organometallic reagents.2 Thus, developing efficient meth-
ods for the conversion of readily available aryl triflates into
aryl halides with wide functional group tolerance is of
interest. Despite considerable effort,7 to date only a few
metal-catalyzed methods for the conversion of aryl and
vinyl triflates to aryl and vinyl halides have been reported.8
We recently disclosed the first example of a direct Pd-
catalyzed conversion of aryl and vinyl triflates to bromides
and chlorides.8d However, the reaction suffered from some
limitations. In particular, the addition of iBu3Al (1.5 equiv)
was required to sequester the formed KOTf that inhibited
(1) (a) Gribble, G. W. Acc. Chem. Res. 1998, 31, 141. (b) Gribble,
G. W. Chem. Soc. Rev. 1999, 28, 335. (c) Gribble, G. W. J. Nat. Prod.
1992, 55, 1353.
(2) Forselectedreviews, see:(a)Knochel,P.;Dohle, W.;Gommermann,
N.; Kneisel, F. F.; Kopp, F.; Korn, T.; Sapountzis, I.; Vu, V. A. Angew.
Chem., Int. Ed. 2003, 42, 4302. (b) Parham, W. E.; Bradsher, C. K. Acc.
Chem. Res. 1982, 15, 300. (c) Hassan, J.; Sevignon, M.; Gozzi, C.; Schulz,
E.; Lemaire, M. Chem. Rev. 2002, 102, 1359.
(3) (a) Wiley, G. A.; Hershkowitz, R. L.; Rein, B. M.; Chung, B. C. J.
Am. Chem. Soc. 1964, 86, 964. (b) Bay, E.; Bak, D. A.; Timony, P. E.;
Leonebay, A. J. Org. Chem. 1990, 55, 3415. (c) Albert, A.; Clark, J. J.
Chem. Soc. 1964, 1666. (d) Bendich, A.; Russell, P. J.; Fox, J. J. J. Am.
Chem. Soc. 1954, 76, 6073. (e) Surrey, A. R.; Cutler, R. A. J. Am. Chem.
Soc. 1954, 76, 1109. (f) Bestmann, H. J.; Schnabel, K. H. Liebigs Ann.
Chem. 1966, 698, 106.
(4) (a) Wulff, W. D.; Peterson, G. A.; Bauta, W. E.; Chan, K.-S.;
Faron, K. L.; Gilbertson, S. R.; Kaesler, R. W.; Yang, D. C.; Murray,
C. K. J. Org. Chem. 1986, 51, 277. (b) Kang, H.; Facchetti, A.; Stern,
C. L.; Rheingold, A. L.; Kassel, W. S.; Marks, T. J. Org. Lett. 2005, 7,
3721. (c) Grunewald, G. L.; Seim, M. R.; Regier, R. C.; Criscione, K. R.
Bioorg. Med. Chem. 2007, 15, 1298. (d) Thompson, A. L. S.; Kabalka,
G. W.; Akula, M. R.; Huffman, J. W. Synthesis 2005, 547.
(5) For selected reviews, see: (a) Ritter, K. Synthesis 1993, 735. (b)
Scott, W. J.; McMurry, J. E. Acc. Chem. Res. 1988, 21, 47.
(6) Bunnett, J. F. Acc. Chem. Res. 1992, 25, 2.
(7) For selected reviews on metal-mediated carbonÀhalogen bond
formation, see: (a) Vigalok, A. Chem.;Eur. J. 2008, 14, 5102. (b)
Sheppard, T. D. Org. Biomol. Chem. 2009, 7, 1043. (c) Grushin, V. V.
Acc. Chem. Res. 2009, 43, 160. (d) For the formation of CÀBr bonds by
Pd-catalyzed reductive elimination, see: Newman, S. G.; Lautens, M. J.
Am. Chem. Soc. 2010, 132, 11416.
(8) (a) Milne, J. E.; Jarowicki, K.; Kocienski, P. J. Synlett 2002, 607.
(b) Shirakawa, E.; Imazaki, Y.; Hayashi, T. Chem. Commun. 2009, 5088.
(c) Watson, D. A.; Su, M. J.; Teverovskiy, G.; Zhang, Y.; Garcia-
Fortanet, J.; Kinzel, T.; Buchwald, S. L. Science 2009, 325, 1661. (d)
Shen, X.; Hyde, A. M.; Buchwald, S. L. J. Am. Chem. Soc. 2010, 132,
14076.
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10.1021/ol202098h
Published on Web 08/24/2011
2011 American Chemical Society