Journal of the American Chemical Society
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ACKNOWLEDGMENTS
Table 3: Scope of alkene in hydroheteroarylation with indolesa
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This work was supported by the Director, Office of Science, of the
U.S. Department of Energy under contract no. DE-AC02-
05CH11231, Grant-in-Aid for Scientific Research on Innovative
Areas “Precise Formation of a Catalyst Having a Specified Field
for Use in Extremely Difficult Substrate Conversion Reactions”
(no. 15H05799) from MEXT, and the ACT-C Program by the
JST. Y.S. thanks the SNSF for a Postdoctoral fellowship. We
thank Dr. Antonio DiPasquale for collecting the crystallographic
data and solving the structure of complex C1 and compound 3v
with instrumentation available from the NIH (S10-RR027172).
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REFERENCES
1 Figure S1 gives a summary of several such structures containing
linear alkyl chains at C2.
2
Bailly, F.; Grimaud, B.; Malejonock, I.; Vayrin,
P. US2013/12729 A1, 2013; Lee, K. L.; Foley, M. A.; Chen, L.;
Behnke, M. L.; Lovering, F. E.; Kirincich, S. J.; Wang, W.; Shim, J.;
Tam, S.; Shen, M. W., H.; Khor, S.; Xu, X.; Goodwin, D. G:; Rama-
rao, M. K.; Nickerson-Nutter, C.; Donahue, F.; Ku, M. S.; Clark, J.
D.; McKew, J. C. J. Med. Chem. 2007, 50, 1380.
3 Bandini, M.; Eichholzer, A. Angew. Chem. Int. Ed., 2009, 48, 9608.
4 Rueping, M.; Nachtsheim, B. J. Beilstein J. Org. Chem. 2010, 6, No.
6.
a Conditions: catalyst: C1: (IPr*OMe)Ni(C6H6); C2: IPrMe / Ni(cod)2; C3:
(IPrMe)Ni(C6H6); indole (0.500 mmol), alkene (0.750 mmol); neat; tem-
b
c
perature, 100 °C. 0.330 mmol scale. indole (0.500 mmol), alkene
(0.500 mmol). d with NaOtBu (0.5 equiv.). e indole (0.500 mmol), alkene
(1.50 mmol). f determined by GC analysis. NMR yields in parentheses.
5 For reactions with (a) activated terminal olefins and Michael ac-
ceptors: Pan, S.; Ryu, N.; Shibata, T. J. Am. Chem. Soc. 2012, 134,
17474; (b) allylic carbonates: Wang, H.; Schroeder, N.; Glorius, F.;
Angew. Chem. Int. Ed. 2013, 52, 5386; (c) allylic alcohols: Shi, Z.;
Boultadakis-Arapinis, M.; Glorius, F. Chem. Commun. 2013, 49, 6489;
(d) vinyl silanes: Ding, Z.; Yoshikai, N. Beilstein J. Org. Chem. 2012,
8, 1536; Schinkel, M.; Marek, I.; Ackermann, L. Angew. Chem. Int.
Ed. 2013, 52, 3977; (e) primary alkyl chlorides: Punji, B.; Song, W.;
Shevchenko, G. A.; Ackermann, L. Chem. Eur. J. 2013, 19, 10605.
6 (a) Grigg, R.; Savic, V. Tetrahedron Lett. 1997, 38, 5737; (b) Yama-
kawa, T.; Yoshikai, N. Chem. Asian J. 2014, 9, 1242.
To gain preliminary mechanistic data on this addition process,
a kinetic isotope effect for the addition of N-methylindole to
alkenes was measured with 2-D,N-Me-indole and N-Me-indole
in separate vessels. The KIE from reactions of the labeled and
unlabeled indole with 1-tridecene was only 1.3, and with nor-
bornene was 1.4. These KIE values suggest that C–H activa-
tion is not turnover-limiting.18 Rather, this KIE is consistent
with reversible C–H activation before an irreversible step.19
12
7 Jiao, L.; Bach, T. J. Am. Chem. Soc. 2011, 133, 12990.
8 Lee, D.-H.; Kwon, K.-H.; Yi, C. S. Science 2011, 333, 1613.
9 Nakao, Y.; Kashihara, N.; Kanyiva, K. S.; Hiyama, T. Angew.
Chem. Int. Ed. 2010, 49, 4451.
The postulated pathway, (Scheme S9) , comprises reversible
C–H activation by a direct transfer of the C-H bond of a
bound arene to the bound alkene without formation of a met-
al-hydride intermediate, as described previously for the hy-
10 Bair, J. S.; Schramm, Y.; Sergeev, A. G.; Clot, E.; Eisenstein, O.;
Hartwig, J. F. J. Am. Chem. Soc. 2014, 136, 13098.
10
droarylations of CF3-containing arenes catalyzed by Ni(IPr)2.
This step has been termed ligand-to-ligand hydrogen transfer
(LLHT) and would be followed by reductive elimination to
form the C-C bond.
11 Nakao, Y.; Yamada, Y.; Kashihara, N.; Hiyama, T. J. Am. Chem.
Soc. 2010, 132, 13666.
12 See supporting information for full details.
13
Scheme S6 in the supporting information gives a detailed
In summary, we have developed a new protocol for hydrohet-
eroarylation of heteroarenes with a Ni-NHC system that is
selective for the linear alkylarene and that tolerates a large
number of functional groups. Further mechanistic studies to
reveal the effect of base and precise elementary steps of the
catalytic cycle are underway.
description of yields obtained in the presence or absence of base for
selected examples.
14 Cornella, J.; Zarate, C.; Martin, R. Chem. Soc. Rev. 2014, 43,
8081; Tobisu, M.; Chatani, N. Acc. Chem. Res. 2015, 48, 1717.
15 Ding, Z.; Yoshikai, N. Angew. Chem. Int. Ed. 2013, 52, 8574.
16 Sevov, C. S.; Hartwig, J.F. J. Am. Chem. Soc. 2013, 135, 2116.
17 We currently do not understand the effect of NaOtBu in this par-
ticular reaction and cannot provide an explanation for this observati-
on.
ASSOCIATED CONTENT
Tables of reaction condition development, additional mechanistic
experiments, full experimental protocols and characterization data for
all new materials. This material is available free of charge via the
18 Simmons, E. M.; Hartwig, J. F. Angew. Chem. Int. Ed. 2012, 51,
3066.
19 The KIE in the reaction of 2-D-benzofuran with 1-decene could
not be obtained because fast exchange of the deuterium label between
the C-2 position of benzofuran and the vinylic position of the terminal
olefin occurred as a competitive reaction (Scheme S11).
AUTHOR INFORMATION
Corresponding Author
jhartwig@berkeley.edu; nakao.yoshiaki.8n@kyoto-u.ac.jp
Notes
The authors declare no competing financial interests.
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