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Organic & Biomolecular Chemistry
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COMMUNICATION
Based on the literature of nickel-catalysed cyanations,17,30,31 the
Scheme 4. Scope of nickel-catalyzed cyanation of heteroaryl
chloridesa
proposed catalytic cycle for this transfDoOrmI: a10t.i1o0n39i/sC7sOhBo0w08n92inA
Scheme 5a,b. Initially, the precatalyst 1a undergoes
transmetallation with Zn(CN)2 to give
eliminating ortho-methylbenzonitrile, gives the solvato complex
. In agreement with this proposal, we observed a small amount
of ortho-methylbenzonitrile in all GC-FID traces of reaction
mixtures. The Ni(0) complex may be stabilized by chloride ions
and undergoes oxidative addition with the aryl halide substrate
to give complex . Following transmetallation with Zn(CN)2 to
give , the desired benzonitrile is produced by reductive
elimination from to reconstitute complex
4, which upon reductively
5
5
6
7
7
5.
In conclusion, a general catalytic cyanation of (hetero)aryl
chlorides under ambient conditions is described. Our
methodology uses an air and moisture stable nickel precatalyst
with a commercially available bidentate phosphine ligand,
XantPhos. This room temperature cyanation of (hetero)aryl
chlorides proceeds smoothly in the presence of Zn(CN)2 and
does not require drying or grinding of the cyanide source.
Advantageously, the procedure does not require drying of the
substrates 3a vs 3l, the more electron-poor 3l afforded the glassware, substrates, or the nickel precatalyst. Our simple and
product in a much higher yield. mild reaction conditions should allow for widespread use of this
The only functional group found not to be tolerant to our protocol.
conditions was the nitro (-NO2) moiety: Hence, para-
nitrochlorobenzene did not show any desired product Acknowledgements: The authors thank: NSERC CREATE
formation. The oxygen transfer reaction from nitro groups to Sustainable Synthesis (CSS) and the University of British
phosphines is well known for nickel phosphine species.29
Columbia for financial support (4YF), and Chaoren Shen (LIKAT)
Surprisingly, comparing the cyanation of aryl chlorides and for assistance with column chromatography.
bromides under the same conditions, we found that conversion
to the benzonitrile products in the latter case were lower. For a
list of aryl bromide substrates which give poor conversions, see
Notes and references
the SI. We explain this unusual observation by the chloride
induced stabilization of active nickel intermediates.
1
2
3
E. B. Lansdon, K. M. Brendza, M. Hung, R. Wang, S.
Mukund, D. Jin, G. Birkus, N. Kutty and X. Liu, J. Med.
Chem., 2010, 53, 4295–4299.
Scheme 5. Activation of precatalyst and mechanistic proposals.
J. I. Mark, H.F., Bikales, N., Overberger, C.G, Menges, G.,
Kroschwitz, Encyclopedia of polymer science and
engineering, Wiley, New York, 2nd edn., 1985, vol. 2.
G. Henrici-Olivé and S. Olivé, in Chemistry, Springer Berlin
Heidelberg, Berlin, Heidelberg, 1979, pp. 123–152.
H. H. Hodgson, Chem. Rev., 1947, 40, 251–277.
T. Sandmeyer, Chem. Ber., 1884, 17, 2650–2653.
K. W. Rosenmund and E. Struck, Chem. Ber., 1919, 52,
1749–1756.
4
5
6
7
J. v. Braun and G. Manz, Liebigs Ann. Chem., 1931, 488,
111–126.
8
T. D. Senecal, W. Shu and S. L. Buchwald, Angew. Chem.
Int. Ed., 2013, 52, 10035–10039.
9
P. Anbarasan, T. Schareina and M. Beller, Chem. Soc. Rev.,
2011, 40, 5049–5067.
10
11
12
13
D. T. Cohen and S. L. Buchwald, Org. Lett., 2015, 17, 202–
205.
Y. Tu, Y. Zhang, S. Xu, Z. Zhang and X. Xie, Synlett, 2014, 25,
2938–2942.
T. Chatterjee, R. Dey and B. C. Ranu, J. Org. Chem., 2014,
79, 5875–5879.
P. Y. Yeung, C. M. So, C. P. Lau and F. Y. Kwong, Org. Lett.,
2011, 13, 648–651.
14
15
L. Cassar, J. Organomet. Chem., 1973, 54, C57–C58.
L. Cassar, M. Foà, F. Montanari and G. P. Marinelli, J.
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