Organic Letters
Letter
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including five-membered heterocycles. This reaction does not
require grinding of the cyanide source, is run under aqueous
conditions, and is easily set up. Finally, the utility of this cyanation
was demonstrated by late-stage cyanation and synthesis of
lersivirine. We anticipate that this palladium-catalyzed cyanation
will be readily integrated into the fields of pharmaceutical and
academic research.
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6254.
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Beller, M. J. Organomet. Chem. 2003, 684, 50−55. (b) Sundermeier, M.;
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4828−4845. (c) Ushkov, A. V.; Grushin, V. V. J. Am. Chem. Soc. 2011,
133, 10999−11005.
ASSOCIATED CONTENT
* Supporting Information
■
S
Experimental procedures, characterization, and spectral data.
This material is available free of charge via the Internet at http://
(13) Senecal, T. D.; Shu, W.; Buchwald, S. L. Angew. Chem., Int. Ed.
2013, 52, 10035−10039.
(14) (a) Anbarasan, P.; Schareina, T.; Beller, M. Chem. Soc. Rev. 2011,
40, 5049−5067. (b) Shim, Y. J.; Lee, H. J.; Park, S. J. Organomet. Chem.
2012, 696, 4173−4178. (c) Zhang, D.; Sun, H.; Zhang, L.; Zhou, Y.; Li,
C.; Jiang, H.; Chen, K.; Liu, H. Chem. Commun. 2012, 48, 2909−2911.
(d) Zou, T.; Feng, X.; Liu, H.; Yu, X.; Yamamoto, Y.; Bao, M. RSC Adv.
2013, 3, 20379−20384.
AUTHOR INFORMATION
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Corresponding Author
Notes
(15) For the use of benzyl cyanide as the cyanide source, see: Wen, Q.;
Jin, J.; Hu, B.; Lu, P.; Wang, Y. RSC Adv. 2012, 2, 6167−6169.
(16) For a palladium-catalyzed cyanation of aryl halides at 65 °C and
heteroaryl halides at 80 °C, see: (a) Anderson, B. A.; Bell, E. C.; Ginah, F.
O.; Harn, N. K.; Pagh, L. M.; Wepsiec, J. P. J. Org. Chem. 1998, 63, 8224−
8228. For a palladium-catalyzed cyanation of aryl halides at 56 °C, see:
(b) Marcantonio, K. M.; Frey, L. F.; Liu, Y.; Chen, Y.; Strine, J.; Phenix,
B.; Wallace, D. J.; Chen, C. Y. Org. Lett. 2004, 6, 3723−3725. For
palladium-catalyzed cyanation at 50 °C for aromatic bromides, see:
(c) Yeung, P. Y.; Tsang, C. P.; Kwong, F. Y. Tetrahedron Lett. 2011, 52,
7038−7041.
(17) Klinkenberg, J. L.; Hartwig, J. F. J. Am. Chem. Soc. 2012, 134,
5758−5761.
(18) For the palladium-catalyzed cyanation of aryl halides at 50−80 °C,
see ref 14. These examples include mainly aryl halides. Six-membered
heterocycles needed to be heated to 80 °C to achieve a large substrate
scope (ref 14a). Additionally, these reports do not contain any examples
of five-membered heterocylces.
The authors declare the following competing financial inter-
est(s): MIT holds or has filed patents on some of the ligands and
precatalysts used in this work, for which S.L.B. receives royalty
payments.
ACKNOWLEDGMENTS
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Financial support for this project was provided by the National
Institutes of Health under award nos. GM46059 (S.L.B.) and
GM108294 (D.T.C.). Ryan S. Shinabery (MIT) is thanked for
the synthesis of precatalysts P1 and P2. We thank Dr. Michael
Pirnot (MIT) and Dr. Yiming Wang (MIT) for help with the
preparation of this manuscript. The content is solely the
responsibility of the authors and does not necessarily represent
the official views of the National Institutes of Health.
(19) For a room-temperature cyanation of aryl bromides and aryl
iodides with Zn(CN)2 in the presence of Pd2(dba)3/PtBu3, see:
Ramnauth, J.; Bhardwaj, N.; Renton, P.; Rakhit, S.; Maddaford, S. P.
Synlett 2003, 2237−2239. This reaction uses an air-sensitive P-t-Bu3
ligand, higher catalyst loadings (5 mol %), an excess of Zn(CN)2 (1.8
equiv), and additional zinc. The substrate scope only includes aryl
bromides and iodides, and there are no examples of five- or six-
membered heterocycles.
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