Incorporation of Carbon Dioxide into Carbamate Directing Groups: Palladium-Catalyzed meta-C–H Olefination and Acetoxylation of Aniline Derivatives

Article abstract of DOI:10.1002/adsc.201700261

Carbon dioxide (CO₂), a readily available, non-toxic, and inexpensive greenhouse gas, is an ideal reagent for carbamate synthesis. For the first time, CO₂ has been efficiently incorporated into a novel nitrile-containing directing group (DG) for meta-C–H activation of anilines under mild conditions. Thus, various aniline derivatives were meta-olefinated with palladium(II) acetate. meta-C–H acetoxylation was also feasible and the carbamate DG could be easily removed under basic conditions. The practicality of substrate preparation, functional group tolerance, and versatility of this method make it a valuable addition to the meta-C–H functionalization of anilines. (Figure presented.).

Full text of DOI:10.1002/adsc.201700261

Title: Incorporation of Carbon Dioxide into Carbamate Directing
Groups: Palladium-Catalyzed meta-C–H Olefination and
Acetoxylation of Aniline Derivatives
Authors: Long Yang, Lei Fu, and Gang Li
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Adv. Synth. Catal. 10.1002/adsc.201700261
Link to VoR: http://dx.doi.org/10.1002/adsc.201700261

10.1002/adsc.201700261
Advanced Synthesis & Catalysis
COMMUNICATION
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Incorporation of Carbon Dioxide into Carbamate Directing
Groups: Palladium-Catalyzed meta-C–H Olefination and
Acetoxylation of Aniline Derivatives
Long Yang,+a,b Lei Fu,+b and Gang Lib,*
a
College of Chemistry, Fuzhou University, Fuzhou 350002, People’s Republic of China
Key Laboratory of Coal to Ethylene Glycol and Its Related Technology, Fujian Institute of Research on the Structure
b
of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002, P. R. China
Phone and fax: (+86)-591-63173547; e-mail: gangli@fjirsm.ac.cn
These authors contributed equally to this work.
+
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
achieved the first ruthenium-catalyzed ortho-C–H
alkenylation of various N-aryloxazolidinones.[4c]
However, in these reports the carbamate substrates
were prepared by using toxic and moisture sensitive
reagents (Scheme 1a),[4a,c] or by indirect synthesis
from phenyl isocyanate[4a] or modified Hofmann
rearrangement of benzamides.[4b] Moreover, these C–
H transformations are limited to ortho-selectivity.
Due to the strong electronic biases, meta-selective C–
H functionalization[9-19] of anilines has proved to be
extremely challenging, and only a few approaches
were reported by the groups of Gaunt,[12a] Yu,[17b,15c,d]
and Ackermann[13c] as well as the group of Li and
Yang.[19] In 2014, Yu and co-workers developed an
Abstract. Carbon dioxide (CO2), a readily available,
nontoxic, and inexpensive greenhouse gas, is an ideal
reagent for carbamate synthesis. For the first time, CO2 has
been efficiently incorporated into a novel nitrile-containing
directing group (DG) for meta-C–H activation of anilines
under mild conditions. Thus, a variety of aniline derivatives
were meta-olefinated with palladium(II) acetate. meta-C–H
acetoxylation was also feasible and the carbamate DG
could be easily removed under basic conditions. The
practicality of substrate preparation, functional group
tolerance, and versatility of this method make it a valuable
addition to meta-C–H functionalization of anilines.
Keywords: aniline; carbon dioxide; carbamate; meta-C–H
activation; palladium catalyst
C–H functionalization has recently emerged as a
powerful method for complex molecule synthesis and
diversification, which is largely relying on directing
groups (DGs) for achieving positional selectivity.[1,2]
Aniline carbamates are widespread in complex
molecules such as natural products and
pharmaceuticals.[3,4] Thus, synthetically useful
methods for their preparation and diversification are
highly desirable. Unlike their isomeric phenol
carbamates,[5] aniline carbamates bearing the intrinsic
carbamate functionality as the potential DG are rarely
explored in C–H activation using transition-metal
catalysts,[6] though directed ortho-metalation[7] of
aniline carbamates and the related anilide[1,8] DGs
have been extensively studied. Recently, Li et al.
disclosed a systematic investigation of diverse aniline
carbamates for ortho-C–H arylation with palladium(II)
acetate.[4a] Later, Moghaddam and co-workers
reported palladium-catalyzed ortho-halogenation of
aniline carbamates under mild conditions.[4b] Most
recently, McMullin, Williams, Frost and co-workers
Scheme 1. Synthetic methods of aniline carbamates.
impressive
conformation-induced
meta-C–H
activation of aniline derivatives directed by a
rationally designed nitrile-containing template[17,18]
with an α-fluorine substitution in the anilide
linkage.[17b] Inspired by this work as well as our
1
This article is protected by copyright. All rights reserved.

10.1002/adsc.201700261
Advanced Synthesis & Catalysis
previous work on meta-C–H activation promoted by
desired olefinated products in 55% combined yield
DGs with a linear coordinating nitrile functionality,[18] (Table 1, Entry 1) with high selectivity (meta/other >
we proposed to synthesize a meta-selective carbamate
DG for anilines to further explore the potential C–H
functionalization of aniline carbamates (Scheme 1b).
We envisioned that such DG could be readily
generated by incorporation of carbon dioxide
(CO2),[20] a readily available, nontoxic, stable, and
inexpensive greenhouse gas, into the carbamate
linkage under mild basic conditions.[21] To the best of
our knowledge, this is the first study on the use of
CO2 to generate a DG for C–H activation of aniline
derivatives.
To examine our hypothesis, we produced 1a' using
CO2 in a multi-gram scale (See the Supporting
Information). Then we synthesized carbamate 2a' by
protecting 1a' with a nosyl group (Table 1), since 1a'
underwent ortho-C–H activation directed by the
carbamate group. C–H-olefination[22] was then
selected as a test reaction to check the effectiveness
of this new meta-DG. Thus, using our previous
reaction conditions,[18] 2a' was treated with ethyl
acrylate, palladium acetate (10 mol%), N-acetyl-
glycine (Ac-Gly-OH, 20 mol%),[17a] and AgOAc (2
equiv) in HFIP at 90 °C for 24 h to provide the
20:1). Further optimization of the reaction revealed
that a methyl substituent at the benzyl position of the
substrate (2a) afforded better results (Entry 2). The
yield was then increased to 65% at a lower
temperature of 80 °C (Entry 3). Notably, 60 mol% of
the Ac-Gly-OH ligand was found to be better while
tuning the loading of ligand (Entries 4 and 5). The
yield of 3a was further improved when Ag2CO3 was
used as the oxidant (Entry 6). To our delight, the
result was improved dramatically when DCE was
used as a co-solvent (Entry 7). Finally, the best yield
was obtained (Entry 9) by increasing the
concentration of the reaction as well as the loading of
Ag2CO3 (Entries 8-10). However, in contrast to our
Table 2. Substrate scope of meta-C–H olefination.[a]
Table 1. Optimization of reaction conditions.[a]
Entry
Oxidant
Solvent
Yield (%)
[mono/di]
55 [5.1/1]
1[b,c]
2[c]
AgOAc
AgOAc
HFIP
HFIP
61 [3.7/1]
65 [4/1]
3
AgOAc
HFIP
4[d]
5[e]
AgOAc
HFIP
70 [3.4/1]
68 [3.3/1]
71 [1.2/1]
88 [1.4/1]
90 [1/1]
AgOAc
HFIP
6
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Cu(OAc)2/O2
HFIP
7[d,f]
8[d,f,g]
9[d,f,g,h]
10[d,f,h]
11[d,i]
HFIP/DCE
HFIP/DCE
HFIP/DCE 94 [1/1][j]
HFIP/DCE
80 [2.3/1]
--[k]
HFIP
[a]Reaction conditions: 2a (0.1 mmol), ethyl acrylate (0.2
mmol), Pd(OAc)2 (10 mol%), Ac-Gly-OH (20 mol%),
oxidant (0.2 mmol), HFIP (1 mL), 24 h, 80 °C. Yield was
1
determined by H NMR with CH2Br2 as internal standard.
(mono/di) denotes the ratio of meta-olefinated and (meta,
meta')-diolefinated products. [b]2a' (0.1 mmol) was used.
[c]90 °C. [d]60 mol% Ac-Gly-OH. [e]80 mol% Ac-Gly-OH.
[f]HFIP/DCE = 1/1 (v/v). [g]Ag2CO3 (0.3 mmol). [h]solvent
(0.7 mL). [i]Cu(OAc)2 (0.05 mmol), O2 (1 atm). [j]Isolated
yield. [k]The reaction is messy. Gly = glycine, Ns = 4-
nitrobenzenesulfonyl, HFIP = hexafluoro-2-propanol.
[a]Reaction conditions: 2 (0.1 mmol), ethyl acrylate (0.2
mmol), Pd(OAc)2 (0.01 mmol), Ac-Gly-OH (0.06 mmol),
Ag2CO3 (0.3 mmol), HFIP/DCE (0.35 mL/0.35 mL), 24 h,
80 °C. Isolated yields. [b]28 h.
2
This article is protected by copyright. All rights reserved.

10.1002/adsc.201700261
Advanced Synthesis & Catalysis
previous study of meta-C–H olefination of benzoic
acid derivatives,[18b] oxygen was not viable as the
terminal oxidant in the presence of copper acetate
(Entry 11).
deficient styrene, was also applicable with this
reaction to give excellent yield of product 5gf, albeit
styrene was not a viable coupling partner.
To examine the versatility of the method with a
different catalytic cycle, meta-acetoxylation was
investigated briefly (Table 4). We were pleased to
find both non-substituted (6a) and mono- and di-
substituted (6c-6r) substrates afforded meta-
acetoxylation products in moderate to good yields
using the oxidation conditions in our previous
study,[18b] although the acetoxylation reactions were
generally less efficient than the above corresponding
olefination reactions.
With the optimized conditions in hand, we
examined the scope of this meta-selective C–H
protocol with a variety of substrates (Table 2).
Substrates with both electron-donating and electron-
withdrawing groups at the ortho-position were well
tolerated (3b-3f). The reaction also proceeded
smoothly with various meta-substituted substrates
(3g-3m). Notably, the chloro and bromo substituents
are compatible with the reaction (3e, 3f, 3k, and 3l),
enabling further elaboration of the olefinated
products. para-Substituted aniline carbamates bearing
methoxy, fluoro, or chloro groups were also viable to
deliver the desired olefinated products in moderate to
good yields (3n-3p). Finally, the method was also
suitable for di-substituted anilines as well as
tetrahydroquinoline carbamate (3q-3s). It should be
notated the meta-selectivity was generally excellent
(meta/other >20:1) for the above substrates.
Table 4. meta-C–H acetoxylation of aniline carbamates.[a]
Table 3. Scope of olefin coupling partners.[a]
[a]Reaction conditions: 2 (0.1 mmol), Pd(OAc)2 (0.01
mmol), Ac-Gly-OH (0.02 mmol), Ac2O (0.5 mmol),
o
PhI(OAc)2 (0.3 mmol), HFIP (1mL), 24 h, 90 C. Isolated
yields. [b]A trace of (m, m')-di-acetoxylated product was
observed.
Finally, the carbamate DG could be removed easily
under mild conditions with K2CO3 in excellent yield
(7, Scheme 2a). Notably, free amine 8 could also be
produced by refluxing 3emono with KOH for two
hours in H2O/MeOH (Scheme 2b).[4a] Interestingly,
hydrolysis of acetoxylated product 6c under the
above conditions afforded nosyl protected aniline 9 in
high yield (Scheme 2c).
[a]Reaction conditions: 2g (0.1 mmol), 4 (0.2 mmol),
Pd(OAc)2 (0.01 mmol), Ac-Gly-OH (0.06 mmol), Ag2CO3
(0.3 mmol), HFIP/DCE (0.35 mL/0.35 mL), 24 h, 80 °C.
Isolated yields. [b]A trace of other isomers were observed.
In conclusion, we have developed a novel meta-C–
H activation DG for aniline derivatives by facile
incorporation of CO2 into the carbamate under mild
basic conditions for the first time. A broad range of
aniline derivatives were efficiently olefinated at the
meta-positions with good functional group tolerance.
meta-C–H acetoxylation was also proved to be viable.
Moreover, the carbamate DG as well as the nosyl
protecting group could be easily cleaved under basic
conditions. All of these features are beneficial for the
potential application of this method in late-stage C–H
functionalization of complex molecules. More direct
use of CO2 in C–H activation reactions is under way
in our laboratory.
The scope of this reaction was further examined
with various olefin coupling partners (Table 3).
Olefination of 2g with methyl methacrylate afford
desired products 5ga in good yield. Trans-2-
butenoate reacted stereoselectively with 2g to give
5gb in moderate yield, though a trace of other
unknown isomers were also observed. Notably, cyclic
tri-substituted olefin was also compatible with this
reaction to give good yield of allylated product (5gc).
Pleasingly, α,β-unsaturated ketone and amide also
afforded olefinated products (5gd and 5ge) in good
yields. However, non-activated alkene such as oct-1-
ene and (E)-oct-3-ene were not compatible coupling
partners. Finally, pentafluorostyrene 4f, an electron
3
This article is protected by copyright. All rights reserved.

10.1002/adsc.201700261
Advanced Synthesis & Catalysis
References
[1] Selected reviews on C–H functionalization: a) T. W.
Lyons, M. S. Sanford, Chem. Rev. 2010, 110, 1147;
b) I. A. Mkhalid, J. H. Barnard, T. B. Marder, J. M.
Murphy, J. F. Hartwig, Chem. Rev. 2010, 110, 890;
c) S. H. Cho, J. Y. Kim, J. Kwak, S. Chang, Chem.
Soc. Rev. 2011, 40, 5068; d) N. Kuhl, M. N.
Hopkinson, J. Wencel-Delord, F. Glorius, Angew.
Chem. 2012, 124, 10382; Angew. Chem. Int. Ed.
2012, 51, 10236; e) G. Song, F. Wang, X. Li, Chem.
Soc. Rev. 2012, 41, 3651; f) G. Rouquet, N. Chatani,
Angew. Chem. 2013, 125, 11942; Angew. Chem. Int.
Ed. 2013, 52, 11726; g) S. A. Girard, T. Knauber, C.-
J. Li, Angew. Chem. 2014, 126, 76; Angew. Chem. Int.
Ed. 2014, 53, 74; h) M. Zhang, Y. Zhang, X. Jie, H.
Zhao, G. Li, W. Su. Org. Chem. Front. 2014, 1, 843;
i) L. Ackermann, Acc. Chem. Res. 2014, 47, 281; j) O.
Daugulis, J. Roane, L. D. Tran, Acc. Chem. Res.
2015, 48, 1053; k) B. Su, Z.-C. Cao, Z.-J. Shi, Acc.
Chem. Res. 2015, 48, 886; l) Z. Chen, B. Wang, J.
Zhang, W. Yu, Z. Liu, Y. Zhang, Org. Chem. Front.
2015, 2, 1107; m) J. He, M. Wasa, K. S. L. Chan, Q.
Shao, J.-Q. Yu, Chem. Rev. 2017, DOI:
10.1021/acs.chemrev.6b00622; n) Z. Dong, Z. Ren, S.
J. Thompson, Y. Xu, G. Dong, Chem. Rev. 2017,
DOI: 10.1021/acs.chemrev.6b00574.
Scheme 2. Removal of the directing group.
Experimental Section
General olefination procedure: To a dry 38 mL sealed
tube (with a Teflon cap) equipped with a magnetic stir bar
was charged with substrate 2 (0.1 mmol, 1.0 equiv),
Pd(OAc)2 (2.3 mg, 0.01 mmol), Ac-Gly-OH (7.0 mg, 0.06
mmol) and Ag2CO3 (83.0 mg, 0.3 mmol) sequentially.
Then HFIP (0.35 mL) and DCE (0.35 mL) were added to
the mixture, followed by ethyl acrylate (21 L, 2.0 equiv).
The tube was then capped and submerged into a preheated
80 °C oil bath. The reaction was stirred for 24-28 h and
cooled to room temperature. The crude reaction mixture
was diluted with EtOAc (5 mL) and filtered through a
short pad of Celite. The sealed tube and Celite pad were
washed with an additional 25 mL of EtOAc. The filtrate
[2] For C–H functionalization reactions in complex
molecule synthesis: a) L. McMurray, F. O'Hara, M. J.
Gaunt, Chem. Soc. Rev. 2011, 40, 1885; b) W. R.
Gutekunst, P. S. Baran, Chem. Soc. Rev. 2011, 40,
1976; c) J. Yamaguchi, A. D. Yamaguchi, K. Itami,
Angew. Chem. 2012, 124, 9092; Angew. Chem. Int.
Ed. 2012, 51, 8960; d) J. Wencel-Delord, F. Glorius,
Nat. Chem. 2013, 5, 369.
1
was concentrated in vacuo, and crude H NMR spectrum
[3] a) A. K. Ghosh, M. Brindisi, J. Med. Chem. 2015, 58,
2895; b) L. Ren, N. Jiao, Chem. Commun. 2014, 50,
3706, and references therein; c) S. S. Chaudhaery,
K. K. Roy, N. Shakya, G. Saxena, S. R. Sammi, A.
Nazir, C. Nath, A. K. Saxena, J. Med. Chem. 2010,
53, 6490.
was taken using CH2Br2 as internal standard. The resulting
residue was purified by flash silica gel chromatography or
preparative thin layer chromatography using petroleum
ether/EtOAc as the eluent to give the desired products.
General acetoxylation procedure: To a dry 38 mL sealed
tube (with a Teflon cap) equipped with a magnetic stir bar
was charged with substrate 2 (0.1 mmol, 1.0 equiv),
Pd(OAc)2 (2.3 mg, 0.01 mmol), Ac-Gly-OH (2.4 mg, 0.02
mmol) and PhI(OAc)2 (96.6 mg, 0.30 mmol). HFIP (1.0
mL) was added to the mixture along the inside wall of the
tube, followed by Ac2O (47 μL, 0.5 mmol). The reaction
tube was then capped. The tube was submerged into a
preheated 90 °C oil bath. The reaction was stirred for 24 h
and cooled to room temperature. The crude reaction
mixture was diluted with EtOAc (5 mL) and filtered
through a short pad of Celite. The sealed tube and Celite
pad were washed with an additional 25 mL of EtOAc. The
filtrate was concentrated in vacuo, and the resulting residue
was purified by flash silica gel chromatography or
preparative thin layer chromatography using petroleum
ether/EtOAc as the eluent to give the desired products.
[4] a) N. Uhlig, C.-J. Li, Chem. Eur. J. 2014, 20, 12066;
b) F. M. Moghaddam, G. Tavakoli, B. Saeednia, P.
Langer, B. Jafari, J. Org. Chem. 2016, 81, 3868; c) J.
A. Leitch, P. B. Wilson, C. L. McMullin, M. F.
Mahon, Y. Bhonoah, I. H. Williams, C. G. Frost, Acs
Catal. 2016, 6, 5520.
[5] Selected examples: a) R. B. Bedford, R. L. Webster,
C. J. Mitchell, Org. Biomol. Chem. 2009, 7, 4853; b)
X. Zhao, C. S. Yeung, V. M. Dong, J. Am. Chem.
Soc. 2010, 132, 5837; c) K. Yamazaki, S.
Kawamorita, H. Ohmiya, M. Sawamura, Org. Lett.
2010, 12, 3978; d) J. Li, C. Kornhaaß, L. Ackermann,
Chem. Commun. 2012, 48, 11343; e) T.-J. Gong, B.
Xiao, Z.-J. Liu, J. Wan, J. Xu, D.-F. Luo, Y. Fu, L.
Liu, Org. Lett. 2011, 13, 3235.
Acknowledgements
We thank the financial support by NSFC (Grant No. 21402198),
the Strategic Priority Research Program of the Chinese Academy
of Sciences (Grant No. XDB20000000), and The 1000 Youth
Talents Program.
[6] For isolated instances of aniline carbamates acting as
DGs: a) D. Kalyani, N. R. Deprez, L. V. Desai, M. S.
Sanford, J. Am. Chem. Soc. 2005, 127, 7330; b) E.
Hernando, R. R. Castillo, N. Rodriguez, R. Gomez
4
This article is protected by copyright. All rights reserved.

10.1002/adsc.201700261
Advanced Synthesis & Catalysis
Arrayas, J. C. Carretero, Chem. Eur. J. 2014, 20,
13854; c) R. Haridharan, K. Muralirajan, C.-H.
Cheng, Adv. Synth. Catal. 2015, 357, 366.
15499; Angew. Chem. Int. Ed. 2015, 54, 15284; f) Z.
Fan, J. Ni, A. Zhang, J. Am. Chem. Soc. 2016, 138,
8470; g) Z.-Y. Li, L. Li, Q.-L. Li, K. Jing, H. Xu, G.-
W. Wang, Chem. Eur. J. 2017, DOI:
10.1002/chem.201700354; h) Z. Ruan, S.-K. Zhang,
C. Zhu, P. N. Ruth, D. Stalke, L. Ackermann, Angew.
Chem. 2017, 129, 2077; Angew. Chem. Int. Ed. 2017,
56, 2045; i) S. Warratz, D. J. Burns, C. Zhu, K.
Korvorapun, T. Rogge, J. Scholz, C. Jooss, D.
Gelman, L. Ackermann, Angew. Chem. 2017, 129,
1579; Angew. Chem. Int. Ed. 2017, 56, 1557.
[7] M. C. Whisler, S. MacNeil, V. Snieckus, P. Beak,
Angew. Chem. 2004, 116, 2256; Angew. Chem. Int.
Ed. 2004, 43, 2206.
[8] Selected examples: a) V. G. Zaitsev, O. Daugulis, J.
Am. Chem. Soc. 2005, 127, 4156; b) S. Yang, B. Li,
X. Wan, Z. Shi, J. Am. Chem. Soc. 2007, 129, 6066;
c) N. R. Deprez, M. S. Sanford, J. Am. Chem. Soc.
2009, 131, 11234; d) F. W. Patureau, F. Glorius, J.
Am. Chem. Soc. 2010, 132, 9982; e) B. Xiao, Y.-M.
Li, Z.-J. Liu, H.-Y. Yang, Y. Fu, Chem. Commun.
2012, 48, 4854.
[14] a) J. Luo, S. Preciado, I. Larrosa, J. Am. Chem. Soc.
2014, 136, 4109; b) X.-Y. Shi, K.-Y. Liu, J. Fan, X.-
F. Dong, J. F. Wei, C.-J. Li, Chem. Eur. J. 2015, 21,
1900; c) Y. Zhang, H. Zhao, M. Zhang, W. Su,
Angew. Chem. 2015, 127, 3888; Angew. Chem. Int.
Ed. 2015, 54, 3817; d) D. Lee, S. Chang, Chem. Eur.
J. 2015, 21, 5364.
[9] Selected reviews on meta-C–H functionalization: a) T.
Truong, O. Daugulis, Angew. Chem. 2012, 124,
11845; Angew. Chem. Int. Ed. 2012, 51, 11677; b) F.
Juliá-Hernández, M. Simonetti, I. Larrosa, Angew.
Chem. 2013, 125, 11670; Angew. Chem. Int. Ed.
2013, 52, 11458; c) C. Martinez, K. Muniz,
ChemCatChem 2013, 5, 3502; d) J. Yang, Org.
Biomol. Chem. 2015, 13, 1930; e) C. G. Frost, A. J.
Paterson, ACS Cent. Sci. 2015, 1, 418; f) J. Li, S. De
Sarkar, L. Ackermann, Top. Organomet. Chem. 2016,
55, 217; g) A. Dey, S. Agasti, D. Maiti, Org. Biomol.
Chem. 2016, 14, 5440.
[15] a) X.-C. Wang, W. Gong, L.-Z. Fang, R.-Y. Zhu, S.
Li, K. M. Engle, J.-Q. Yu, Nature 2015, 519, 334; b)
Z. Dong, J. Wang, G. Dong, J. Am. Chem. Soc. 2015,
137, 5887; c) P. Wang, M. E. Farmer, X. Huo, P. Jain,
P.-X. Shen, M. Ishoey, J. E. Bradner, S. R.
Wisniewski, M. D. Eastgate, J.-Q. Yu, J. Am. Chem.
Soc. 2016, 138, 9269; d) H. Shi, P. Wang, S. Suzuki,
M. E. Farmer, J.-Q. Yu, J. Am. Chem. Soc. 2016, 138,
14876; e) J. Han, L. Zhang, Y. Zhu, Y. Zheng, X.
Chen, Z.-B. Huang, D.-Q. Shi, Y. Zhao, Chem.
Commun. 2016, 52, 6903; f) P.-X. Ling, K. Chen, B.-
F. Shi, Chem. Commun. 2017, 53, 2166.
[10] For selective examples of meta-C–H borylation and
silylation: a) J.-Y. Cho, M. K. Tse, D. Holmes, R. E.
Maleczka, M. R. Smith, Science 2002, 295, 305; b) T.
Ishiyama, J. Takagi, J. F. Hartwig, N. Miyaura,
Angew. Chem. 2002, 114, 3182; Angew. Chem. Int.
Ed. 2002, 41, 3056; c) C. Cheng, J. F. Hartwig,
Science 2014, 343, 853; d) Y. Kuninobu, H. Ida, M.
Nishi, M. Kanai, Nat. Chem. 2015, 7, 712; e) R.
Bisht, B. Chattopadhyay, J. Am. Chem. Soc. 2016,
138, 84; f) H. J. Davis, M. T. Mihai, R. J. Phipps, J.
Am. Chem. Soc. 2016, 138, 12759.
[16] For more meta-selective functionalizations: a) B.-J.
Li, Z.-J. Shi, Chem. Sci. 2011, 2, 488; b) M. Ye, G.-L.
Gao, J.-Q. Yu, J. Am. Chem. Soc. 2011, 133, 6964; c)
X. Cong, H. Tang, C. Wu, X. Zeng, Organometallics
2013, 32, 6565; d) J. Zhang, Q. Liu, X. Liu, S. Zhang,
P. Jiang, Y. Wang, S. Luo, Y. Li, Q. Wang, Chem.
Commun. 2015, 51, 1297.
[17] Selected examples of meta-C–H functionalization
using nitrile or pyridine based templates: a) D. Leow,
G. Li, T.-S. Mei, J.-Q. Yu, Nature 2012, 486, 518; b)
R.-Y. Tang, G. Li, J.-Q. Yu, Nature 2014, 507, 215;
c) S. Lee, H. Lee, K. L. Tan, J. Am. Chem. Soc. 2013,
135, 18778; d) M. Bera, A. Modak, T. Patra, A. Maji,
D. Maiti, Org. Lett. 2014, 16, 5760; e) M. Bera, A.
Maji, S. K. Sahoo, D. Maiti, Angew. Chem. 2015,
127, 8635; Angew. Chem. Int. Ed. 2015, 54, 8515; f)
M. Bera, S. K. Sahoo, D. Maiti, ACS Catal. 2016, 6,
3575; g) L. Chu, M. Shang, K. Tanaka, Q. Chen, N.
Pissarnitski, E. Streckfuss, J.-Q. Yu, ACS Cent. Sci.
2015, 1, 394; h) S. Bag, R. Jayarajan, R. Mondal, D.
[11] a) Y.-H. Zhang, B.-F. Shi, J.-Q. Yu, J. Am. Chem.
Soc. 2009, 131, 5072; b) L. Zhou, W. Lu,
Organometallics 2012, 31, 2124; c) Y.-N. Wang, X.-
Q. Guo, X.-H. Zhu, R. Zhong, L.-H. Cai, X.-F. Hou,
Chem. Commun. 2012, 48, 10437.
[12] For meta-C–H arylation using copper and aryl
iodonium salts: a) R. J. Phipps, M. J. Gaunt, Science
2009, 323, 1593; b) H. A. Duong, R. E. Gilligan, M.
L. Cooke, R. J. Phipps, M. J. Gaunt, Angew. Chem.
2011, 123, 483; Angew. Chem. Int. Ed. 2011, 50, 463;
c) Y. Yang, R. Li, Y. Zhao, D. Zhao, Z. Shi, J. Am.
Chem. Soc. 2016, 138, 8734.
Maiti,
Angew.
Chem.
2017,
DOI:
[13] a) O. Saidi, J. Marafie, A. E. W. Ledger, P. M. Liu,
M. F. Mahon, G. Kociok-Köhn, M. K. Whittlesey, C.
G. Frost, J. Am. Chem. Soc. 2011, 133, 19298; b) N.
Hofmann, L. Ackermann, J. Am. Chem. Soc. 2013,
135, 5877; c) J. Li, S. Warratz, D. Zell, S. De Sarkar,
E. E. Ishikawa, L. Ackermann, J. Am. Chem. Soc.
2015, 137, 13894; d) C. J. Teskey, A. Y. W. Lui, M.
F. Greaney, Angew. Chem. 2015, 127, 11843; Angew.
Chem. Int. Ed. 2015, 54, 11677; e) Q. Yu, L. Hu, Y.
Wang, S. Zheng, J. Huang, Angew. Chem. 2015, 127,
10.1002/ange.201611360; Angew. Chem. Int. Ed.
2017, DOI: 10.1002/anie.201611360; i) H.-J. Xu, Y.
Lu, M. E. Farmer, H.-W. Wang, D. Zhao, Y.-S. Kang,
W.-Y. Sun, J.-Q. Yu, J. Am. Chem. Soc. 2017, 139,
2200.
[18] a) S. Li, H. Ji, L. Cai, G. Li, Chem. Sci. 2015, 6,
5595; b) S. Li, L. Cai, H. Ji, L. Yang, G. Li, Nat.
Commun. 2016, 7, 10443.
5
This article is protected by copyright. All rights reserved.

10.1002/adsc.201700261
Advanced Synthesis & Catalysis
[19] G. Li, X. Ma, C. Jia, Q. Han, Y. Wang, J. Wang, L.
Guo, M. Zhang, H. Jiang, Chem. Eur. J. 2015, 21,
Yu, S. Yang, Chem. Commun. 2017, 53, 1261.
14314.
[20] For reviews on the use of CO2 in organic synthesis: a)
T. Sakakura, J. C. Choi, H. Yasuda, Chem. Rev. 2007,
107, 2365; b) K. Huang, C.-L. Sun, Z.-J. Shi, Chem.
Soc. Rev. 2011, 40, 2435; c) Z.-Z. Yang, L.-N. He, J.
Gao, A.-H. Liu, B. Yu, Energy Environ. Sci. 2012, 5,
6602; d) M. Aresta, A. Dibenedetto, A. Angelini,
Chem. Rev. 2014, 114, 1709; e) M. Borjesson, T.
Moragas, D. Gallego, R. Martin, ACS Catal 2016, 6,
6739; f) Q. Liu, L. Wu, R. Jackstell, M. Beller, Nat.
Commun. 2015, 6, 5933; g) C. Martín, G. Fiorani, A.
W. Kleij, ACS Catalysis 2015, 5, 1353.
[22] Selected reviews on C–H olefination: a) C. Jia, T.
Kitamura, Y. Fujiwara, Acc. Chem. Res. 2001, 34,
633; b) T. Satoh, M. Miura, Chem. Eur. J. 2010, 16,
11212; c) C. S. Yeung, V. M. Dong, Chem. Rev.
2011, 111, 1215; d) J. Le Bras, J. Muzart, Chem. Rev.
2011, 111, 1170.
[21] For use of CO2 in carbamate synthesis: a) W.
McGhee, D. Riley, K. Christ, Y. Pan, B. Parnas, J.
Org. Chem. 1995, 60, 2820; b) R. N. Salvatore, S. I.
Shin, A. S. Nagle, K. W. Jung, J. Org. Chem. 2001,
66, 1035; c) D. B. Dell'Amico, F. Calderazzo, L.
Labella, F. Marchetti, G. Pampaloni, Chem. Rev.
2003, 103, 3857; d) W. Xiong, C. Qi, Y. Peng, T.
6
This article is protected by copyright. All rights reserved.

10.1002/adsc.201700261
Advanced Synthesis & Catalysis
COMMUNICATION
Incorporation of Carbon Dioxide into Carbamate
Directing Groups: Palladium-Catalyzed meta-C–H
Olefination and Acetoxylation of Aniline
Derivatives
Adv. Synth. Catal. Year, Volume, Page – Page
Long Yang,+a,b Lei Fu,+b and Gang Lib,*
7
This article is protected by copyright. All rights reserved.