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ChemComm
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DOI: 10.1039/C7CC09290C
COMMUNICATION
Journal Name
increasing the substrate scope, scalable capacity, synthetic
applications and catalytic mechanism of this novel cross-
coupling chemistry are underway in our laboratory.
Table 3. Substrate scope investigation for alkyl halides
This work was financially supported by the Canada Research
Chair (Tier 1) foundation, FQRNT (CCVC), NSERC, CFI, and
McGill University. We also thank CSC (China Scholarship
Council) for the sponsorship of the visiting scholar fellowship
(No. 201608430077, Dr. J. Tang), National Postdoctoral
Program for Innovative Talents (No. BX201700110, Dr. L. Lv)
and China Postdoctoral Science Foundation Funded Project
(No. 2017M623270, Dr. L. Lv).
Conflicts of interest
The authors declare no competing financial interest.
Notes and references
1.
2.
3.
N. Kishner, J. Russ. Phys. Chem. Soc, 1911, 43, 582-595.
L. Wolff, Justus Liebigs Ann. Chem., 1912, 394, 86-108.
J. T. Kuethe, K. G. Childers, Z. Peng, M. Journet, G. R.
Humphrey, T. Vickery, D. Bachert and T. T. Lam, Org.
Process Res. Dev., 2009, 13, 576-580.
D. J. Cram and M. R. V. Sahyun, J. Am. Chem. Soc., 1962,
84, 1734-1735.
Reaction conditions: 1a (0.4 mmol), N2H4·H2O (0.48 mmol), 2 (0.1 mmol),
Ni(COD)2 (0.01 mmol), PMe3 (0.05 mmol), DBU (0.2 mmol), THF (450 μL), 50 oC,
24, 36, 48, 60, 72 or 120 h, under N2. See supporting information for
4.
experimental details. Yields of isolated product
noted. Trace yields of were detected by GC-MS. [a] Yields were determined by
GC-MS and 1H NMR of the crude reaction mixture using 1,3,5-
trimethoxybenzene as internal standard because of difficult isolation of
3 are given unless otherwise
3
5.
6.
M. Huang, J. Am. Chem. Soc., 1946, 68, 2487-2488.
M. E. Furrow and A. G. Myers, J. Am. Chem. Soc., 2004,
126, 5436-5445.
3.
7.
8.
L. Caglioti and M. Magi, Tetrahedron, 1963, 19, 1127-
1131.
M. F. Grundon, H. B. Henbest and M. D. Scott, J. Chem.
Soc., 1963, 0, 1855-1858.
D. J. Weix, Acc. Chem. Res., 2015, 48, 1767-1775.
R. Jana, T. P. Pathak and M. S. Sigman, Chem. Rev., 2011,
111, 1417-1492.
X.-F. Wu, H. Neumann and M. Beller, Chem. Soc. Rev.,
2011, 40, 4986-5009.
N. Rodriguez and L. J. Goossen, Chem. Soc. Rev., 2011, 40,
5030-5048.
C. Mauger and G. Mignani, Adv. Synth. Catal., 2005, 347,
773-782.
To investigate the synthetic potential of this reaction, we
applied the optimized protocol to synthesize 1,2,3-trimethoxy-
5-(4-methoxybenzyl)benzene (Scheme 2, 3b), an important
antimitotic agent.22 With 3,4,5-trimethoxybenzaldehyde 1b
and 4-methoxyiodobenzene 2b as substrates, 75% yield of 3b
was obtained, which is higher than the reported one (60%).22
The result extends the applicability of this cross-coupling
reaction.
9.
10.
11.
12.
13.
14.
15.
Z. Shao and H. Zhang, Chem. Soc. Rev., 2012, 41, 560-572.
A. Takemiya and J. F. Hartwig, J. Am. Chem. Soc., 2006,
128, 14800-14801.
16.
17.
Y. Xia and J. Wang, Chem. Soc. Rev., 2017, 46, 2306-2362.
H. Wang, X.-J. Dai and C.-J. Li, Nat. Chem., 2017, 9, 374-
378.
W. Wei, X.-J. Dai, H. Wang, C. Li, X. Yang and C.-J. Li,
Chem. Sci., 2017, 8, 8193-8197.
N. Chen, X.-J. Dai, H. Wang and C.-J. Li, Angew. Chem. Int.
Ed., 2017, 56, 6260-6263.
X.-J. Dai, H. Wang and C.-J. Li, Angew. Chem. Int. Ed.,
2017, 56, 6302-6306.
G. Cahiez and A. Moyeux, Chem. Rev., 2010, 110, 1435-
1462.
M. Cushman, D. Nagarathnam, D. Gopal, H. M. He, C. M.
Lin and E. Hamel, J. Med. Chem., 1992, 35, 2293-2306.
Scheme 2 Synthesis of 1,2,3-trimethoxy-5-(4-methoxybenzyl)benzene. Reaction
conditions: 1b (0.4 mmol), N2H4·H2O (0.48 mmol), 2b (0.1 mmol), Ni(COD)2 (0.01
mmol), PMe3 (0.05 mmol), DBU (0.2 mmol), THF (450 μL), 48h, under N2. Yield of
isolated product is given.
18.
19.
20.
21.
22.
Conclusions
In summary, a novel nickel-catalyzed cross-coupling reaction
between aldehydes and aryl halides has been developed via
the Wolff-Kishner hydrazone intermediates. The method
provides a simple and efficient strategy for cross-couplings
using naturally abundant aldehydes and readily accessible
hydrazine, complementary to the use of organometallic
reagents in the classical cross-coupling reactions. It merges the
two powerful synthetic methods in chemistry and opens up
new routes in designing chemical synthesis. Further studies on
4 | J. Name., 2012, 00, 1-3
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