Nickel-catalyzed direct thioetherification of β-C(sp3)-H bonds of aliphatic amides

Article abstract of DOI:10.1021/acs.orglett.5b00471

The nickel-catalyzed β-thioetherification of unactivated C(sp³)-H bond of propionamides is established with the assistance of 8-aminoquinoline auxiliary, leading to the β-thio carboxylic acid derivatives. A broad range of functional groups is compatible with this thioetherfication reaction. The process represents the first successful example of metal-catalyzed C-S bond formation from unactivated C(sp³)-H bonds.

Full text of DOI:10.1021/acs.orglett.5b00471

Letter
pubs.acs.org/OrgLett
Nickel-Catalyzed Direct Thioetherification of β‑C(sp3)−H Bonds of
Aliphatic Amides
Cong Lin,† Wenlong Yu,† Jinzhong Yao,† Bingjie Wang,† Zhanxiang Liu,† and Yuhong Zhang*,†,‡
†Department of Chemistry, Zhejiang University, Hangzhou 310027, China
‡State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, China
S
* Supporting Information
ABSTRACT: The nickel-catalyzed β-thioetherification of
unactivated C(sp3)−H bond of propionamides is established
with the assistance of 8-aminoquinoline auxiliary, leading to
the β-thio carboxylic acid derivatives. A broad range of
functional groups is compatible with this thioetherfication
reaction. The process represents the first successful example of metal-catalyzed C−S bond formation from unactivated C(sp3)−H
bonds.
evelopment of applicable methods for the catalytic
inferior to the palladium species. Herein, we report a new
3
Dfunctionalization of unactivated of sp C−H bonds remains approach to β-thio carboxylic acid derivatives by direct
thioetherfication of β-sp3 C−H bonds of propionamides with
a pressing task in current organometallic and synthetic organic
chemistry.1 Over the past decades, significant advances have been
disulfides, in which the 8-aminoquinoline auxiliary plays the
crucial role. The eco-friendly and cheap nickel exhibited the
unprecedented catalytic power for the construction of C−S bond
from unactivated sp3 C−H bond.
made in the formation of new C−C or C−X bonds through the
metal-catalyzed activation of C(sp2)−H bonds of arenes.2,3
However, the functionalization of unactivated C(sp3)−H bonds
is still a particularly difficult challenge owing to its inertness. The
pioneering work by Sanford4 and Yu5 has demonstrated that the
direct fuctionalization of sp3 C−H bonds could be achieved by
the use of the directing groups. More recently, a number of
elegant transformations of sp3 C−H bonds have been
established6−9 by employing the bidentate directing group
since a seminal report by Daugulis in 2005.10 Despite this
remarkable progress, most of the examples of the sp3 C−H bond
fuctionalization are focused on the formation of C−C, C−O and
C−N bonds. The selective construction of C−S bonds from inert
C(sp3)−H is completely undeveloped.
The prevalence of sulfur atom in myriad molecules of
biological interest and functional materials motivates the
development of methods to streamline the introduction of sulfur
atoms into organic molecules. Catalytic methods for C−S bond
formation represent a fundamentally important transformation
and occupies a prominent position in modern synthetic organic
chemistry.11,12 The development of a new, general, catalytic
system for C−S bond construction from sp3 C−H bonds would
be quite appealing. However, it is well-accepted that the strong
binding of sulfur species, in particular by thiols and disulfides
(RSH and R2S2), to transition metals may result in the
deactivation of metal catalysts. Furthermore, the most presently
used method for sp3 C−H activation by Pd(II)/Pd(IV) catalysis
requires oxidants such as PhI(OAc)2, which might damage the
sulfur substrates.13 To address these problems, the development
of new catalytic systems is highly desired. Since a Ni(II)/Ni(IV)
catalysis works very well for the arylation of sp3 C−H bonds in the
absence of oxidant,14 and since the prevalence of nickel catalysis,
we envisioned that nickel catalysts should not be inherently
Very recently, nickel has been demonstrated to possess the
intrinsic catalytic potential for unactivated sp3 C−H bonds by
Chatani’s and Ge’s groups.14a,b In light of these excellent
achievements, we explored the thioetherification of β-C(sp3)−
H bonds of aliphatic amides with disulfides by using nickel as the
catalyst. We initially selected a variety of commercially available
nickel salts at 10 mol % loading to examine the thioetherification
reaction of amide 1a and disulfide 2a of 2 equiv of Na2CO3 at 140
°C for 24 h (Table 1). Various nickel salts, including NiBr2, NiCl2,
and NiI2, catalyzed this reaction to give thioether 3a in acceptable
conversion (Table 1, entries 1−3), but Ni(OTf)2 exhibited
obviously higher reactivity, furnishing 3a in 68% yield (entry 4).
Ni(OAc)2 showed higher reactivity, but the dithioetherification
product was generated to give the 57% monothioetherification
product as well as 14% dithioetherification product (Table 1,
entry 5). Ni(acac)2 was found to be less effective for this
transformation, and Ni(COD)2 was almost inactive (entries 6
and 7). As an activating reagent, the addition of TBAI promoted
the reaction, and an obvious loss of reactivity was observed in the
absence of TBAI (Table 1, entry 8). Replacing the additive of
TBAI with TBAB or NaI led to a lower conversion (Table 1,
entries 9 and 10), while CsI and CuI almost halted the reaction
(Table 1, entries 11 and 12). The efficiency of the reaction was
also significantly affected by the ligands. The commonly used
nitrogen and phosphine ligands, such as phenanthroline (1,10-
phen), PPh3, dppe, Xantphos, showed little effect on the reaction
(Table 1, entries 13−17). The significant function of the amino
Received: February 14, 2015
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.5b00471
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
a,b
Table 1. Optimization of Reaction Conditions
Scheme 1. Substrate Scope of Disulfide
b
entry
catalyst
NiBr2
additive
ligand
yield (%)
1
TBAI
TBAI
TBAI
TBAI
TBAI
TBAI
TBAI
Ac-Gly-OH
Ac-Gly-OH
Ac-Gly-OH
Ac-Gly-OH
Ac-Gly-OH
Ac-Gly-OH
Ac-Gly-OH
Ac-Gly-OH
Ac-Gly-OH
Ac-Gly-OH
Ac-Gly-OH
Ac-Gly-OH
63
65
64
68
2
NiCl2
3
NiI2
4
Ni(OTf)2
Ni(OAc)2
Ni(acac)2
Ni(COD)2
Ni(OTf)2
Ni(OTf)2
Ni(OTf)2
Ni(OTf)2
Ni(OTf)2
Ni(OTf)2
Ni(OTf)2
Ni(OTf)2
Ni(OTf)2
Ni(OTf)2
Ni(OTf)2
Ni(OAc)2
Ni(OTf)2
c
5
71 (4:1)
6
36
<5
7
8
40
9
TBAB
NaI
46
10
11
12
13
14
15
16
17
18
19
20
63
CsI
27
CuI
trace
56
TBAI
TBAI
TBAI
TBAI
TBAI
TBAI
TBAI
TBAI
1,10-Phen
PPh3
58
50
dppe
40
Xantphos
PhCO2H
trace
48
a
Reactions were carried out by using 1a (0.2 mmol), 2 (0.6 mmol),
d
c,e
o-NBA
79 (2.5:1)
Ni(OTf)2 (0.02 mmol), Na2CO3 (2 equiv), TBAI (4 equiv), Ac-Gly-
b
f
Ac-Gly-OH
trace
OH (0.04 mmol), DMF (0.6 mL), N2, 140 °C, 24 h. Isolated yield by
flash column chromatography.
a
Reaction conditions: 1a (0.2 mmol), 1,2-di-p-tolyldisulfane 2a (0.4
mmol), Ni salt (0.02 mmol), Na2CO3 (2 equiv), ligand (0.04 mmol),
and additive (4 equiv), DMF (0.6 mL) in N2 at 140 °C for 24 h.
corresponding thioetherification product 3am. An effort to use
aliphatic disulfides as the substrates failed. By an extension of this
reaction, the analogous 1,2-diphenyl diselenide was found to
react with 1a under the reaction conditions to yield 40% of the
corresponding selenide 3an.
b
c
Isolated yield, Q = 8-quinolinyl. The ratio of mono- and
d
dithioetherification products was presented in parentheses. o-NBA
e
= o-nitrobenzoic acid. 1,2-Bis(4-methoxyphenyl)disulfane 2e was
f
used. In the presence of 2 equiv of zinc powder.
This thioetherification reaction was compatible with a variety
of the amide substrates as shown in Scheme 2. The amide
substrates bearing β-methyl groups with three α-substitutents
participated in the thioetherification reaction to provide the
corresponding β-thio amides including mono- and dithioether-
ification in moderate yields (Scheme 2, 4be−ke). The
regioselectivity of the reaction was always such that the β-methyl
group is preferred over the β-methylene and γ-methyl groups
(Scheme 2, 4be−ke). The amide substrates without a β-methyl
group were inactive under the reaction conditions. In addition, a
tertiary α-carbon atom in the amide substrates was required for
the success of the thioetherification. The substrates with one β-
methyl group delivered the monothioetherification products
(Scheme 2, 4le−ne).
In the case of 1-methyl-N-(quinolin-8-yl)cyclobutanecarbox-
amide 1o, the monothioetherification product 4oe was obtained
in 37% yield, and the ortho-thioetherification of cyclobutane-
carboxamide occurred to give the corresponding ortho-function-
alized cyclobutanecarboxamide product 4oe′ in 40% yield
(Scheme 3). The results of NOESY experiments demonstrated
the correlation of β-methyl group with the hydrogen of the
thioether carbon in the cyclobutane ring (see the Supporting
Information), illustrating the cis configuration of the thioether
with the amide directing group.
acid ligands on the transformation was observed, and the use of
20 mol % Ac-Gly-OH could improve the efficiency of the reaction
to increase the yield from 56% to 68% (Table 1, entries 4 and 13).
Among the carboxylic acid ligands screened (Table 1, entries 4,
18, and 19), o-nitrobenzoic acid exhibited an unexpected effecton
the reaction, although the products were a mixture of 56% mono-
and 23% dithioetherification. In the presence of 2 equiv of zinc
powder, the reaction was entirely inhibited (Table 1, entry 20).
With the optimal reaction conditions in hand, we next
examined the scope of the disulfides in this new thioetherification
protocol (Scheme 1). In general, the disulfides reacted with both
steric and electronic variations on the aryl ring under these
reaction conditions. It was found that the disulfides with an
electron-rich aryl group showed higher reactivity and gave slightly
higher yields than the substrates with an electron-deficient aryl
group. When 1,2-bis(4-methoxyphenyl)disulfane was used as the
substrate, the dithioetherification product 3ae′ was isolated in
14% yield besides the 59% monothioetherification product 3ae.
The steric hindrance significantly influenced the transformation.
For instance, in the case of o-methylphenyl disulfide, a significant
amount of amide 1a was recovered, and the thioether 3ac was
only isolated in 45% yield. The aryl−halogen bonds were
tolerated under the reaction conditions: products 3ag−ak were
obtained efficiently without any thioetherification products of
C−X bonds. β-Naphthalene disulfide participated in the reaction
smoothly to give the products 3al in a 42% yield. Remarkably, 2-
methylfuran-3-disulfide was a viable substrate to afford the
The primary mechanistic study revealed that the addition of
radical scavenging reagents such as 2,2,6,6-tetramethyl-1-
piperidinyloxy (TEMPO) or 2,6-di-tert-butyl-4-methylphenol
(BHT) had a poor impact on the reaction (Scheme 4, eq 1). This
B
DOI: 10.1021/acs.orglett.5b00471
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a,b
D exchange in the β-methyl group for the deuterium-labeled
starting amide D3-1l was observed again (Scheme 4, eq 3),
implicating that the cyclometalation step from intermediate A to
intermediate B is reversible (Scheme 5). Based on these results
Scheme 2. Substrate Scope of Aliphatic Amides
Scheme 5. Proposed Reaction Mechanism
a
Reactions were carried out by using 1 (0.2 mmol), 2e (0.6 mmol),
Ni(OAc)2 (0.02 mmol), Na2CO3 (2 equiv), TBAI (4 equiv), o-
nitrobenzoic acid (0.04 mmol), DMF (0.6 mL), N2, 140 °C, 24 h.
and previous reports,14a,16 a plausible reaction pathway of Ni(II)/
Ni(IV) is proposed as shown in Scheme 5. First, the Ni(II) center
coordinates with the nitrogen in 8-aminoquinoline auxiliary
followed by a ligand exchange under basic condition to form the
intermediate A. The cyclometalation of intermediate A gives
intermediate B, which undergoes the oxidative addition with
disulfide to generate the intermediate C. The reductive
elimination of the intermediate C forms the intermediate D,
which liberates the product and regenerates the Ni(II) species
through the exchange of anions and protonation to fulfill the
cycle.
b
Isolated combined yield of mono- and disubstituted products.
c
Purified by GPC.
Scheme 3. Thioetherification of Cyclobutanecarboxamide
Scheme 4. Control Experiment and Deuterium-Labeling
Result
In summary, we have developed a new method for the 8-
aminoquinolinyl-assisted thioetherification of the β-sp3 C−H
bond of propioamides with good functional group tolerance. For
the first time, abundant and low cost nickel is applied as the
catalyst for the successful construction of C−S bonds by the
direct coupling of disulfide with C(sp3)−H bonds. The reaction
shows high regioselectivity for a preferential thioetherification of
C(sp3)−H bonds of methyl groups over the methylene C(sp3)−
H bonds. Further investigations to extend the reaction scope and
elucidate mechanism are in progress.
ASSOCIATED CONTENT
■
S
* Supporting Information
General procedures, analytical data, and copies of H and 13C
1
NMR spectra. This material is available free of charge via the
Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
result is incompatible with a Ni(I)/Ni(III) pathway that might
involve the single-electron-transfer process.14b,15 On the other
hand, the reaction became very sluggish when 10 mol %
Ni(COD)2 or the combination of 10 mol % Ni(OAc)2 and 2
equiv of zinc powder was used (Table 1, entries 7 and 20),
indicating that Ni(0) is quite difficult to initiate the reaction.
It was found that the D content in the amide D3-1l after 4 h
decreased from >99% to 89% in the absence of disulfide under the
standard reaction conditions (Scheme 4, eq 2). This result
illustrates that the C−H cleavage step occurs and is reversible. To
gain further evidence for H/D exchange, the deuterium-labeling
experiment of disulfide was carried out. The occurrence of the H/
■
*E-mail: yhzhang@zju.edu.cn.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Funding from National Basic Research Program of China (No.
2011CB936003), Natural Science Foundation of China (No.
21272205, 21472165), and the Program for Zhejiang Leading
Team of S&T Innovation (2011R50007) is acknowledged.
C
DOI: 10.1021/acs.orglett.5b00471
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
(9) For examples of C(sp3)−H bonds intramolecular amination, see:
Wu, X.; Zhao, Y.; Zhang, G.; Ge, H. Angew. Chem., Int. Ed. 2014, 53,
3706.
(10) Zaitsev, V.; Shabashov, D.; Daugulis, O. J. Am. Chem. Soc. 2005,
127, 13154.
REFERENCES
■
(1) For selected examples of functionalization of unactivated C (sp3)−
H bonds, see: (a) Lieg
́
ault, B.; Fagnou, K. Organometallics 2008, 27,
4841. (b) McNeill, E.; Bois, J. D. J. Am. Chem. Soc. 2010, 132, 10202.
(c) Stowers, K. J.; Fortner, K. C.; Sanford, M. S. J. Am. Chem. Soc. 2011,
133, 6541. (d) Michaudel, Q.; Thevenet, D.; Baran, P. S. J. Am. Chem. Soc.
2012, 134, 2547. (e) Simmons, E. M.; Hartwig, J. F. Nature 2012, 483,
70. (f) Liu, B.; Zhou, T.; Li, B.; Xu, S.; Song, H.; Wang. Angew. Chem., Int.
Ed. 2014, 53, 4191. (g) Wang, N.; Li; Li, L.; Xu, S.; Song, H.; Wang, B. J.
Org. Chem. 2014, 79, 5379. (h) Zhang, L.-S.; Chen, G.; Wang; Guo, Q.-
Y.; Zhang, X.-S.; Pan, F.; Chen, K.; Shi, Z.-J. Angew. Chem., Int. Ed. 2014,
53, 3899. (i) Ammann, S. E.; Rice, G. T.; White, M. C. J. Am. Chem. Soc.
2014, 136, 10834.
(11) For C−S bond formation, see: (a) Hartwig, J. F. Acc. Chem. Res.
2008, 41, 1534. (b) Kondo, T.; Mitsudo, T. Chem. Rev. 2000, 100, 3205.
(c) Chauhan, P.; Mahajan, S.; Enders, D. Chem. Rev. 2014, 114, 8807.
(d) Shen, C.; Zhang, P.; Sun, Q.; Bai, S.; Hor, T. S. A.; Liu, X. Chem. Soc.
Rev. 2015, 44, 291. (e) Ley, S. V.; Thomas, A. W. Angew. Chem., Int. Ed.
2003, 42, 5400. (f) Tran, L. D.; Popov, I.; Daugulis, O. J. Am. Chem. Soc.
2012, 134, 18237. (g) Yang, Y.; Hou, W.; Qin, L.; Du, J.; Feng, H.; Zhou,
B.; Li, Y. Chem.Eur. J. 2014, 20, 416. (h) Yan, X.-B.; Gao, P.; Yang, H.-
B.; Li, Y.-X.; Liu, X.-Y.; Liang, Y.-M. Tetrahedron 2014, 70, 8730.
(i) Saravanan, P.; Anbarasan, P. Org. Lett. 2014, 16, 848.
(12) (a) Nielsen, S. F.; Nielsen, E.; Olsen, G. M.; Liljefors, T.; Peters, D.
J. Med. Chem. 2000, 43, 2217. (b) Herradura, P. S.; Pendola, K. A.; Guy,
R. K. Org. Lett. 2000, 2, 2019. (c) De Martino, G.; Edler, M. C.; La
Regina, G.; Coluccia, A.; Barbera, M. C.; Barrow, D.; Nicholson, R. I.;
Chiosis, G.; Brancale, A.; Hamel, E.; Artico, M.; Silvestri, R. J. Med. Chem.
2006, 49, 947. (d) Gangjee, A.; Zeng, Y.; Talreja, T.; McGuire, J. J.;
Kisliuk, R. L.; Queener, S. F. J. Med. Chem. 2007, 50, 3046.
(e) Samarasinghe, K. T. G.; Godage, D. N. P. M.; VanHecke, G. C.;
Ahn, Y.-H. J. Am. Chem. Soc. 2014, 136, 11566. (f) Short, M. D.; Xie, Y.;
Li, L.; Cassidy, P. B.; Roberts, J. C. J. Med. Chem. 2003, 46, 3308.
(g) Kritzinger, E. C.; Bauer, F. F.; duToit, W. J. J. Agric. Food Chem. 2013,
61, 269. (h) Jobron, L.; Hummel, G. Org. Lett. 2000, 2, 2265.
(13) (a) He, G.; Zhao, Y.; Zhang, S.; Lu, C.; Chen, G. J. Am. Chem. Soc.
2012, 134, 3. (b) Nadres, E. T.; Daugulis, O. J. Am. Chem. Soc. 2012, 134,
7. (c) He, G.; Zhang, S. Y.; Nack, W. A.; Li, Q.; Chen, G. Angew. Chem.,
Int. Ed. 2013, 52, 11124. (d) Ju, L.; Yao, J.; Wu, Z.; Liu, Z.; Zhang, Y. J.
Org. Chem. 2013, 78, 10821.
(2) For selected reviews of C(sp2)−H bond functionalization, see:
(a) Colby, D. A.; Bergman, R. G.; Ellman, J. A. Chem. Rev. 2010, 110, 624.
(b)Lyons, T. W.; Sanford, M. S. Chem. Rev. 2010, 110, 1147. (c) Wencel-
Delord, J.; Droge, T.; Liu, F.; Glorius, F. Chem. Soc. Rev. 2011, 40, 4740.
(d) Ackermann, L. Acc. Chem. Res. 2014, 47, 281.
(3) For selected examples of C(sp2)−H bonds, see: (a) Wang, D.-H.;
Engle, K. M.; Shi, B.-F.; Yu, J.-Q. Science 2010, 327, 315. (b) Patureau, F.
W.; Glorius, F. J. Am. Chem. Soc. 2010, 132, 9982. (c) Xiao, B.; Gong, T.-
J.; Xu, J.; Liu, Z.-J.; Liu, L. J. Am. Chem. Soc. 2011, 133, 1466. (d) Kwak, J.;
Ohk, Y.; Jung, Y.; Chang, S. J. Am. Chem. Soc. 2012, 134, 17778. (e) Tang,
C.; Jiao, N. J. Am. Chem. Soc. 2012, 134, 18924. (f) Wang, C.; Chen, H.;
Wang, Z.; Chen, J.; Huang, Y. Angew. Chem., Int. Ed. 2012, 51, 7242.
(g) Li, G.; Leow, D.; Wan, L.; Yu, J.-Q. Angew. Chem., Int. Ed. 2013, 52,
1245. (h) Liu, B.; Fan, Y.; Gao, Y.; Sun, C.; Xu, C.; Zhu, J. J. Am. Chem.
Soc. 2013, 135, 468. (i) Matsubara, T.; Asako, S.; Ilies, L.; Nakamura, E. J.
Am. Chem. Soc. 2014, 136, 646. (j) Rouquet, G.; Chatani, N. Angew.
Chem., Int. Ed. 2013, 52, 11726. (k) He, R.; Huang, Z.-T.; Zheng, Q.-Y.;
Wang, C. Angew. Chem., Int. Ed. 2014, 53, 4950. (l) Grigorjeva, L.;
Daugulis, O. Angew. Chem., Int. Ed. 2014, 53, 10209. (m) Aihara, Y.;
Chatani, N. J. Am. Chem. Soc. 2013, 135, 5308.
(14) (a) Aihara, Y.; Chatani, N. J. Am. Chem. Soc. 2014, 136, 898.
(b) Wu, X.; Zhao, Y.; Ge, H. J. Am. Chem. Soc. 2014, 136, 1789. (c) Wu,
X.; Zhao, Y.; Ge, H. Chem.Eur. J. 2014, 20, 9530. (d) Li, M.; Dong, J.;
Huang, X.; Li, K.; Wu, Q.; Song, F.; You, J. Chem. Commun. 2014, 50,
3944. (e) Iyanaga, M.; Aihara, Y.; Chatani, N. J. Org. Chem. 2014, 79,
11922.
(4) Desai, L. V.; Hull, K. L.; Sanford, M. S. J. Am. Chem. Soc. 2004, 126,
9542.
(5) Chen, X.; Goodhue, C. E.; Yu, J.-Q. J. Am. Chem. Soc. 2006, 128,
12634.
(6) For examples of C(sp3)−H bonds functionalization by using
bidentate directing groups, see: (a) Reddy, B. V. S. L.; Reddy, R.; Corey,
E. J. Org. Lett. 2006, 8, 3391. (b) Feng, Y.; Chen, G. Angew. Chem., Int. Ed.
2010, 49, 958. (c) Feng, Y.; Wang, Y.; Landgraf, B.; Liu, S.; Chen, G. Org.
Lett. 2010, 12, 3414. (d) He, G.; Chen, G. Angew. Chem., Int. Ed. 2011,
50, 5192. (e) Gutekunst, W. R.; Gianatassio, R.; Baran, P. S. Angew.
Chem., Int. Ed. 2012, 51, 7507. (f) Tran, L. D.; Daugulis, O. Angew.
Chem., Int. Ed. 2012, 51, 5188. (g) Hoshiya, N. T. K.; Arisawa, M.; Shuto,
S. Org. Lett. 2013, 15, 6202. (h) Pan, F.; Shen, P.-X.; Zhang, L.-S.; Wang,
X.; Shi, Z.-J. Org. Lett. 2013, 15, 4758. (i) Nadres, E. T.; Santos, G. I.;
Shabashov, D.; Daugulis, O. J. Org. Chem. 2013, 78, 9689. (j) Shang, R.;
Ilies, L.; Matsumoto, A.; Nakamura, E. J. Am. Chem. Soc. 2013, 135, 6030.
(k) Fan, M.; Ma, D. Angew. Chem., Int. Ed. 2013, 52, 12152. (l) Zhang,
Q.; Chen, K.; Rao, W.; Zhang, Y.; Chen, F.- J.; Shi, B.-F. Angew. Chem.,
Int. Ed. 2013, 52, 13588. (m) Gu, Q.; Al Mamari, H. H.; Graczyk, K.;
Diers, E.; Ackermann, L. Angew. Chem., Int. Ed. 2014, 53, 3868.
(n) Wang, Z.; Ni, J.; Kuninobu, Y.; Kanai, M. Angew. Chem., Int. Ed. 2014,
53, 3496.
(15) (a) Chmielewski, P. J.; Latos-Grazynski, L. Inorg. Chem. 1997, 36,
840. (b) Renz, A. L.; Perez, L. M.; Hall, M. B. Organometallics 2011, 30,
6365. (c) Neupane, K. P.; Gearty, K.; Francis, A.; Shearer, J. J. Am. Chem.
Soc. 2007, 129, 14605. (d) Higgs, A. T.; Zinn, P. J.; Simmons, S. J.;
Sanford, M. S. Organometallics 2009, 28, 6142. (e) Breitenfeld, J.;Ruiz, J.;
Wodrich, M. D.; Hu, X. J. Am. Chem. Soc. 2013, 135, 12004. (f) Biswas,
S.; Weix, D. J. J. Am. Chem. Soc. 2013, 135, 16192.
(16) (a) Terao, J.; Kambe, N. Acc. Chem. Res. 2008, 41, 1545. (b) Higgs,
A. T.; Zinn, P. J.; Sanford, M. S. Organometallics 2010, 29, 5446.
(7) For examples of C(sp3)−H bond alkylations and alkynylations, see:
(a) Shabashov, D.; Daugulis, O. J. Am. Chem. Soc. 2010, 132, 3965.
(b) Zhang, S. Y.; Li, Q.; He, G.; Nack, W. A.; Chen, G. J. Am. Chem. Soc.
2013, 135, 12135. (c) Zhang, S. Y.; He, G.; Nack, W. A.; Zhao, Y.; Li, Q.;
Chen, G. J. Am. Chem. Soc. 2013, 135, 2124. (d) Ano, Y.; Tobisu, M.;
Chatani, N. J. Am. Chem. Soc. 2011, 133, 1298.
(8) For examples of acetoxylation and alkoxylation of unactivated
C(sp3)−H bonds, see: (a) Rit, R. K.; Yadav, M. R.; Sahoo, A. K. Org. Lett.
2012, 14, 3724. (b) Wang, Z.; Kuninobu, Y.; Kanai, M. Org. Lett. 2014,
16, 4790. (c) Zhang, S. Y.; He, G.; Zhao, Y.; Wright, K.; Nack, W. A.;
Chen, G. J. Am. Chem. Soc. 2012, 134, 7313. (d) Chen, F.-J.; Zhao, S.; Hu,
F.; Chen, K.; Zhang, Q.; Zhang, S.-Q.; Shi, B.-F. Chem. Sci. 2013, 4, 4187.
(e) Shan, G.; Yang, X.; Zong, Y.; Rao, Y. Angew. Chem., Int. Ed. 2013, 52,
13606.
D
DOI: 10.1021/acs.orglett.5b00471
Org. Lett. XXXX, XXX, XXX−XXX