Iridium(III)-Catalyzed Regioselective Carbenoid Insertion C–H Alkylation by α-Diazotized Meldrum's Acid

Article abstract of DOI:10.1002/ejoc.201601212

A practical and straightforward protocol for Ir^III-catalyzed regioselective carbenoid insertion C–H alkylation mediated by α-diazotized Meldrum's acid was developed. The assistance of external additives and oxidants was not needed, and the developed Ir^IIIcatalysis proceeds in a highly efficient manner (e.g., mild reaction conditions, short reaction times and excellent regioselectivity) and demonstrates good compatibility with several privileged substrates, such as valuable N-(2-pyrimidyl)indoles, phenylpyridines, and the marketed drug edaravone and its analogues, and thus provides a good complement to previous methods for the rapid construction of the corresponding alkylated products.

Full text of DOI:10.1002/ejoc.201601212

A Journal of
Accepted Article
Title: Ir(III)-catalyzed Regioselective Carbenoid Insertion C−H Alkylation by α-
diazotized Meldrum’s Acid
Authors: Honggui Lv; William Xu; Kunhua Lin; Jingjing Shi; Wei Yi
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201601212
Link to VoR: http://dx.doi.org/10.1002/ejoc.201601212
Supported by

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COMMUNICATION
Ir(III)-catalyzed Regioselective Carbenoid Insertion C−H Alkylation
by α-diazotized Meldrum’s Acid
†[a,b]
†[b]
[a]
[b]
[b]
Honggui Lv,
William L. Xu, Kunhua Lin, Jingjing Shi* and Wei Yi*
Abstract: A novel, practical and straightforward protocol via Ir(III)-
catalyzed regioselective carbenoid insertion C−H alkylation
Rh(III)-catalyzed reactions, the mandatory addition of the
additive was usually necessary for the high catalytic efficiency,
mediated by α-diazotized Meldrum’s acid has been described herein. in spite of avoiding the use of external oxidant. Moreover, in
In no need of the assistance of any external additives and oxidants,
the developed Ir(III) catalysis proceeds in a highly efficient manner
sharp contrast to chain diazo compounds, the cyclic diazo
compounds that used as versatile ACOSPs were much less
[8,9]
(e.g. mild reaction condition, shorter reaction time and excellent
documented in the literature,
especially in Ir(III)-catalyzed
regioselectivity) and demonstrates good compatibility with several
privileged substrates, such as valuable N-(2-pyrimidyl)indoles,
phenylpyridines, and the marketed drug-Edaravone and its analogs,
thus providing a good complement to previous methods for the rapid
construction of their corresponding alkylated products.
C−H functionalization, for which only two examples have been
[
9a]
[9b]
reported by the groups of Wang
and Ramana.
Nevertheless, the corresponding Ag salt additives were also
found to be involved in their developed reactions. Undoubtedly,
further development of a simple and efficient Ir(III)-catalyzed
carbenoid insertion C−H functionalization using cyclic diazo
compounds as the ACOSPs, with no need of the assistance of
any external oxidants and additives, is still of prime synthetic
value and quite needful in view of green and sustainable
chemistry.
Introduction
The direct regioselective activation of ubiquitous C−H bonds for
tandem constructing C−C and/or C−Het bonds has attracted
considerable attention in modern synthetic chemistry since it
holds great potential in reshaping traditional organic synthesis
Inspired by the above information and in combination with
the recent breakthroughs in the field of Ir(III)-catalyzed C−H
[
10]
activation,
we herein disclose a simple (no need of any
[
1]
procedures. As a result, a tremendous number of elegant
examples from transition-metal catalyzed and directing group
external additives and oxidants), efficient (commonly for 2 h),
and straightforward (one-pot construction of valuable 2-acetate
substituted indole products) Ir(III) catalytic system for
regioselective carbenoid insertion C−H alkylation of indoles,
which was mediated by α-diazotized Meldrum’s acid and MeOH
(eqn (1)). The extension of the developed Ir(III) catalytic system
to other important substrates, such as classical phenylpyridines
(eqn (2)), the marketed drug-Edaravone(eqn (3)) and N-
methoxybenzamide(eqn (4)) as well, has also been
demonstrated successfully for the first time, and thus giving the
corresponding alkylated products in a step-economical fashion.
(
DG)-assisted direct C−H functionalization have been
[2,3]
extensively reported in the past decades.
Generally, the
involvement of an external oxidant is indispensable to the
turnover of the catalytic cycle in the C−H activation reactions.
However, it also often leads to additional costs and production of
unwanted by-products. Therefore, though it is challenging, it is
highly desirable to achieve the transition-metal-catalyzed C−H
activation for the cascade formation of C−C and/or C−Het bonds
without the assistance of any external oxidants.
To address this issue, a versatile approach employing an
auto-cleavable oxidazing-substrate precursor (ACOSP) as the
[4,5]
coupling partner has been disclosed in recent years.
Among
these developed ACOSPs, diazo compounds play a particularly
[
5]
prominent role due to their intrinsic advantages such as high
efficiency, mild reaction conditions, and excellent
chemoselectivity. Following the pioneering work of Yu and
[
6]
coworkers, and to date, remarkable progress has been made
in the Rh(III)-catalyzed carbenoid insertion C−H functionalization
with diazo compounds derived from malonates and β-ketoesters.
[
7]
Despite these advances, there is room for innovation, both in
developing a new and simple catalyst system and in improving
the currently limited substrate scope. For example, in the above
[
[
a]
b]
Department of Chemistry, Shanghai University, 99 Shang-Da Road,
Shanghai 200444, China
VARI/SIMM Center, Center for Structure and Function of Drug
Targets, CAS-Key Laboratory of Receptor Research, Shanghai
Institute of Materia Medica, Chinese Academy of Sciences, 501
Haike Road, Shanghai 201203, China
Results and Discussion
At the outset, we examined this Ir(III)-catalyzed and α-diazotized
Meldrum’s acid-mediated carbenoid insertion reaction in MeOH
employing commercially available [Cp*Ir(Cl) ] as the active
2
E-mail: yiwei.simm@simm.ac.cn, shijingjing@simm.ac.cn
H. Lv and W. L. Xu contributed equally to this work.
catalyst, and using N-(2-pyrimidyl)-functionalized indole 1a as
†
the model substrate since it has given a success story in our
Supporting information for this article is given via a link at the end of
the document.
[8d,11]
previous studies.
To our delight, the anticipated product 3a
was cleanly generated in 83% isolated yield under the initial
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European Journal of Organic Chemistry
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COMMUNICATION
[
11a,12]
conditions (Table 1, entry 1), in which the inherently reactive C-3
position of the indole core was untouched. Subsequently, an
attempt to either increase or decrease the reaction temperature
both clearly inhibited the process (entries 2-3), implying that a
balance between the reactivity and the substrate decomposition
might exist within the reaction. Notably, the introduction of
found in many PPARγ modulators,
this reaction provides
an attractive strategy for the rapid and efficient synthesis of new
potential PPARγ modulators for anti-diabetic drug discovery.
After reviewing the aforementioned results, we concluded
that MeOH has two key roles both as a solvent and as a reagent
in the carbenoid insertion C−H activation reaction. To further
AgOAc and Ag(SbF
6
)
2
to the current Ir(III) catalyst system did
3
confirm this, CD OD, instead of MeOH, was subjected to the
not improve the reaction efficiency (entries 4-5), although
previous reports have demonstrated that the Ag salt could
activate the transition-metal catalyst in highly efficient manner.
reaction at first (Scheme 2a). The result demonstrated that it
was proceeded smoothly to deliver the methyl-deuterated 3q in
good yield, along with additional deuterium incorporation at the
C2-α- and C3-positions of the indole (for detail, see ESI†).
Additionally, running the reaction in EtOH also worked well to
give the desired product 3r in a synthetically useful yield
(Scheme 2b). Overall, these results not only further corroborated
our reasoning but also provided an insight into the reaction
mechanism.
[
2,9]
Gratifyingly, reducing the catalyst loading from 5 mol % to
2.5 mol % led to the isolation of 3a in an equivalent yield of 81%
(
entry 6). Finally, the control experiments indicated that no
desired product was formed in the absence of catalyst or N-(2-
pyrimidyl) group (entries 7-8). In summary, the optimal
conditions of the carbenoid insertion C−H alkylation were
o
[
Cp*Ir(Cl)
2
] (2.5 mol %) at 100 C in MeOH for 2 h under air.
a
Table 1 Selected optimization of reaction conditions
b
T
Yield
(%)
83
Entry
R
Catalyst system (mol %)
o
(
C)
1
2
3
4
5
6
7
8
9
2-Pyrimidyl
2-Pyrimidyl
2-Pyrimidyl
2-Pyrimidyl
2-Pyrimidyl
2-Pyrimidyl
H
[Cp*IrCl
[Cp*IrCl
[Cp*IrCl
[Cp*IrCl
[Cp*IrCl
2
2
2
2
2
]
]
]
]
]
2
2
2
2
2
(5)
100
80
c
(5)
67
(5)
120
100
100
100
100
100
100
71
76
59
81
0
(5), AgOAc(20)
(5), AgSbF
6
(20)
[Cp*IrCl
[Cp*IrCl
2
]
2
(2.5)
]
2 2
(5)
2-Pyrimidyl
2-Pyrimidyl
----------------------
[Cp*RhCl (2.5)
0
d
2
]
2
73
a
2 2
Reaction conditions: 1a (0.22 mmol, 1.1 eq), 2 (0.2 mmol, 1.0 eq), [Cp*IrCl ]
b
c
(
X mol %), MeOH (1.0 mL), 2 h, under air. Isolated yields. Reaction for 12 h.
Scheme 1 Scope of indoles. Reaction conditions:1a-p (0.22 mmol), 2 (0.20
d
Reaction for 24 h, 23% start material 2 was recovered.
mmol), [Cp*IrCl ] (2.5 mol%), MeOH (1.0 mL), 2 h, under air; yields refer to
2
2
isolated yields.
With the optimized conditions in hand, we sought to examine
the scope of indoles and the generality of this reaction, and the
results were given in Scheme 1. In general, the indole substrate
bearing the substituent either at the C3- (1b), C4- (1c), C5- (1d–
k), C6- (1l–o), or C7- (1p) position all efficiently coupled with α-
diazotized Meldrum’s acid 2 in MeOH to give the corresponding
C2-ethyl acetate substituted indoles in moderate to good yields
(
52–88%) and with exclusive regionselectivities, in which both
electron-donating and -withdrawing groups were also all well
tolerated regardless of the electronic properties of the
substituent on the indole skeleton. Moreover, the reaction
showed good compatibility with a wide range of valuable
functional groups including fluoro (3d), chloro (3e and 3l), bromo
Scheme 2 The investigation for the role ofmethanol. Reaction conditions: 1a
0.22 mmol), 2 (0.20 mmol), [Cp*IrCl (2.5 mol %), alcohol (1.0 mL), 2 h,
under air; yields refer to isolated yields.
(
2 2
]
(
3f and 3m), and methoxy (3h and 3o), cyano (3i), ester (3j)
substituents. Notably, indole 1k with bulkier BnNHCO
a
substituent was also found to be quite compatible, thus providing
the desired product 3k in 74% yield. Since the BnNHCO-
substituted indole part has represented a key structural motif
We next performed two different experiments to unveil the
nature of the reaction mechanism. First, the reversibility of the
C–H activation step in the Ir(III) catalytic system was defined by
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European Journal of Organic Chemistry
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COMMUNICATION
3
running the reaction in CD OD in the absence of α-diazotized
Meldrum’s acid 2. As illustrated in Scheme 3a, after stirring the
reaction for 0.5 h, a significant deuterium incorporation of 1a
was detected by NMR analysis (for C-2 position, D : H > 20 : 1;
for C-3 position, D : H = 6.7 : 1), revealing that the Ir(III)-
[
13]
catalyzed C2–H bond activation process is largely reversible.
Subsequently, an intermolecular competition experiment
between differently substituted indoles was conducted to
delineate the action mode of the reaction (Scheme 3b). To this
end, the result revealed electron-rich indoles to be inherently
more reactive (e.g. 3h/3j = 4.2 : 1), suggesting that they are
better substrates than electron-deficient indoles, and also
implying that the C–H activation reaction may be via an internal
[
14]
electrophilic substitution (IES)-type mechanism.
Considering the remarkable versatility displayed by the Ir(III)
catalytic system, we proceeded to expand its synthetic utility for
the carbenoid insertion C−H alkylation of other substrates
(
Scheme 4). We first selected classical phenylpyridine 4a and
Scheme 3 Mechanistic experiments.
the marketed drug-Edaravone 6a as the corresponding model
substrates for this exploration, as such transformation has not
yet been reported in the field of Ir(III)-catalyzed C−H
functionalization. As expected, the coupling with 4a occurred
successfully to give the alkylated product in a good yield. Very
interestingly, the reaction with Edaravone could also be run
smoothly without difficulty, and an alkylation/annulation product
7a was then obtained in a decent yield and with a faster reaction
process (0.5 h vs 2 h) though regioselective carbenoid insertion
[15]
C–H activation, C-C coupling, and cyclization cascade.
Encouraged by the above results, finally several
phenylpyridines (4a-c), Edaravone analogs (6a-c) and N-
methoxybenzamide was used to further test the availability of
the established Ir(III) catalysis. As shown in Scheme 4, α-
diazotized Meldrum’s acid coupled efficiently with these selected
substrates to deliver the corresponding products 5b-c, 7b-c and
9
with excellent regioselectivities and in synthetically useful
yields (70-78%). Intriguingly, switching pyridyl to quinolyl also
furnished the desired product 5d in 50% yield. Taken together,
these results not only illustrated the remarkable robustness of
this Ir(III)-catalyzed system but also provided a highly attractive
strategy to construct new analogs of Edaravone for immediate
drug screening.
Conclusions
In summary, we have developed the first Ir(III)-catalyzed and
carbenoid insertion C−H alkylation of indoles with α-diazotized
Meldrum’s acid giving direct access to 2-acetate substituted
indoles with excellent regioselectivities and functional group
2 2
tolerance and in moderate to good yields, where only [Cp*IrCl ]
was used as the catalyst system and neither extra additive nor
oxidant were required. Further extension of the simple and
convenient Ir(III) catalysis to classical phenylpyridine and the
marketed drug-Edaravone substrates also produced the
satisfactory results. Thus, these versatile reactions presented
provide a good complement to previous methods for the
construction of the corresponding target products. We expect
the developed Ir(III) catalytic system to evoke more C–H
activation reactions for alternate and step-economical synthesis
of other privileged building blocks.
Scheme
4 The investigation for synthetic utility of the Ir(III) catalytic
system using phenylpyridines, the marketed drug-Edaravone and its analogs
as substrates. Reaction conditions: 4 or 6 or 8 (0.22 mmol), 2 (0.20 mmol),
[
Cp*IrCl
2 2
] (2.5 mol %), MeOH (1.0 mL), 2 h or 0.5 h, under air. yields refer to
a
isolated yields. Reaction for 8 h.
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COMMUNICATION
Experimental Section
Q. Yu, Nature 2014, 515, 389-393; j) R. B. Dateer, S. Chang, J. Am.
Chem. Soc. 2015, 137, 4908-4911; k) W. H. Jeon, J. Y. Son, J. E.
Kim, P. H. Lee, Org Lett. 2016, 18, 3498-3501; l) L. Li, H. Wang, S.
Yu, X. Yang, X. Li, Org Lett. 2016, 18, 3662-3665.
Supporting Information (see footnote on the first page of this
article): Experimental procedures, compound characterization
[
5]
For selected reviews, see: a) H. M. L. Davies, J. R. Manning, Nature
1
13
data, and copies of the H NMR and C NMR spectra.
2
008, 451, 417-424; b) M. P. Doyle, R. Duffy, M. Ratnikov, L. Zhou,
Chem. Rev. 2010, 110, 704-724; c) J. Barluenga, C. Valdés, Angew.
Chem., Int. Ed. 2011, 50, 7486-7500; d) Z. Shao, H. Zhang, Chem.
Soc. Rev. 2012, 41, 560-572; e) Q. Xiao, Y. Zhang, J. Wang, Acc.
Chem. Res. 2013, 46, 236-247; f) Y. Xia, Y. Zhang, J. Wang, ACS
Catal. 2013, 3, 2586-2598; g) D. Qian, J. Zhang, Chem. Soc. Rev.
Acknowledgements
We thank the Youth Innovation Promotion Association CAS, the
Sanofi-SIBS Yong Faculty Award, the National Natural Science
Foundation of China (81502909), and the Shanghai Municipal
Natural Science Foundation (15ZR1447800) for financial support
on this study.
2
015, 44, 677-698; h) L. Liu, J. Zhang, Chem. Soc. Rev. 2016, 45,
06-516; i) B. Wang, D. Qiu, Y. Zhang, J. Wang, Beilstein J. Org.
5
Chem. 2016, 12, 796-804.
[
[
6]
7]
W. W. Chan, S. F. Lo, Z. Zhou, W. Y. Yu, J. Am. Chem. Soc. 2012
134, 13565-13568.
,
For the latest examples on Rh(III)-catalyzed carbenoid insertion
C−H functionalization with diazo compounds, see: a) G.-D. Tang,
C.-L. Pan, X. Li, Org. Chem. Front. 2016, 3, 87-90; b) P. Bai, X. F.
Huang, G. D. Xu, Z. Z. Huang, Org. Lett. 2016, 18, 3058-3061; c) W.
Hou, Y. Yang, Y. Wu, H. Feng, Y. Li, B. Zhou, Chem. Commun.
Keywords: Ir(III)-catalyzed • C−H alkylation • indole • α-
diazotized Meldrum’s Acid
[
[
1]
2]
J. Q. Yu, Z. J. Shi, C–H Activation, Springer: Berlin, Germany, 2010.
2
016, 52, 9672-9675; d) X. G. Li, M. Sun, Q. Jin, K. Liu, P. N. Liu, J.
For selected reviews on transition-metal catalyzed C−H
functionalization, see: a) G. Song, F. Wang, X. Li, Chem. Soc. Rev.
Org. Chem. 2016, 81, 3901-3910; e) Y. S. Lu, W. Y. Yu, Org
Lett. 2016, 18, 1350-1353; f) Z. Qi, S. Yu, X. Li, Org. Lett. 2016, 18,
2
012, 41, 3651-3678; b) D. A. Colby, A. S. Tsai, R. G. Bergman and
7
00-703; g) Y. Xie, X. Chen, X. Liu, S. J. Su, J. Li, W. Zeng, Chem.
J. A. Ellman, Acc. Chem. Res., 2012, 45, 814-825; c) N. Kuhl, M. N.
Hopkinson, J. Wencel-Delord, F. Glorius, Angew. Chem., Int. Ed.
Commun. 2016, 52, 5856-5859; h) D. Das, A. Biswas, U. Karmakar,
S. Chand, R. Samanta, J. Org. Chem. 2016, 81, 842-848; (i) R. B.
Dateer, S. Chang, Org. Lett. 2016, 18, 68-71; j) P. Sun, Y. Wu, Y.
Huang, X. Wu, J. Xu, H. Yao, A. Lin, Org. Chem. Front. 2016, 3, 91-
2
012, 51, 10236-10254; (d) S. I. Kozhushkov, L. Ackermann, Chem.
Sci. 2013, 4, 886-896; e) J. Wencel-Delord, F. Glorius, Nat. Chem.
2
2
2
013, 5, 369-375; f) L. Ackermann, Acc. Chem. Res. 2014, 47, 281-
95; g) Y. Zhang, X. Jie, H. Zhao, G. Li, W. Su, Org. Chem. Front.
014, 1, 843-895; h) C. X. Zhuo, C. Zheng, S. L. You, Acc. Chem.
9
5; (k) J. Wang, M. Wang, K. Chen, S. Zha, C. Song, J. Zhu, Org.
Lett., 2016, 18, 1178-1181.
[
[
[
8]
9]
a) X.-Z. Yu, S.-J. Yu, J. Xiao, B.-S. Wan, X.-W. Li, J. Org. Chem.
Res. 2014, 47, 2558-2573; i) F. Chen, T. Wang, N. Jiao, Chem. Rev.
014, 114, 8613-8661; j) R. He, Z. T. Huang, Q. Y. Zheng, C. Wang,
2
2
013, 78, 5444-5452; b) Y. Zhang, J. Zheng, S. Cui, J. Org. Chem.
014, 79, 6490-6500; c) J.-Y. Son, S. Kim, W. H. Jeon, P. H. Lee,
2
Tetrahedron Lett. 2014, 55, 5705-5713; k) Y. F. Han, G. X. Jin,
Chem. Soc. Rev. 2014, 43, 2799-2823; l) C. Liu, J. Yuan, M. Gao,
S. Tang, W. Li, R. Shi, A. Lei, Chem. Rev. 2015, 115, 12138-12204;
m) G. Song, X. Li, Acc. Chem. Res. 2015, 48, 1007-1020; n) K. Shin,
H. Kim, S. Chang, Acc. Chem. Res. 2015, 48, 1040-1052; o) Z.
Chen, B. Wang, J. Zhang, W. Yu, Z. Liu, Y. Zhang, Org. Chem.
Front. 2015, 2, 1107-1295; p) T. Gensch, M. N. Hopkinson, F.
Glorius , J. Wencel-Delord, Chem. Soc. Rev. 2016, 45, 2900-2936.
For the representative examples, see: a) D. R. Stuart, P. Alsabeh, M.
Kuhn, K. Fagnou, J. Am. Chem. Soc. 2010, 132, 18326-18339; b) M.
P. Huestis, L. Chan, D. R. Stuart, K. Fagnou, Angew. Chem., Int. Ed.
Org. Lett. 2015, 17, 2518-2521; d) J. Shi, Y. Yan, Q. Li, H. E. Xu, W.
Yi, Chem. Commun. 2014, 50, 6483-6486.
For reported examples on Ir(III)-catalyzed C−H functionalization with
cyclic diazo compounds, see: a) S.-S. Zhang, C.-Y. Jiang, J.-Q.
Wu, X.-G. Liu, Q. Li, Z.-S. Huang, D. Li, H. Wang, Chem. Commun.
2
015, 51, 10240-10243; b) R. S. Phatake, P. Patel, C. V. Ramana,
Org. Lett. 2016, 18, 2828-2831.
10] For selected examples, see: a) J. Campos, J. López−Serrano, E.
Álvarez, E. Carmona, J. Am. Chem. Soc. 2012, 134, 7165-7175; b)
J. Ryu, J. Kwak, K. Shin, D. Lee, S. Chang, J. Am. Chem. Soc.
[
3]
2
013, 135, 12861-12868; c) M. Itoh, K. Hirano, T. Satoh, Y. Shibata,
K. Tanaka, M. Miura, J. Org. Chem. 2013, 78, 1365-1370; d) F. Xie
Z. Qi S. Yu, X. Li, J. Am. Chem. Soc. 2014, 136, 4780-4787; e)
2
011, 50, 1338-1341; c) W. Zhen, F. Wang, M. Zhao, Z. Du, X. Li,
Angew. Chem. Int. Ed. 2012, 51, 11819-11823; d) T. Gong, B. Xiao,
W. Cheng, W. Su, J. Xu, Z. Liu, L. Liu, Y. Fu, J. Am. Chem. Soc.
，
，
J. Kim, S. Chang, Angew. Chem., Int. Ed. 2014, 53, 2203-2207; f) H.
Kim, K. Shina, S. Chang, J. Am. Chem. Soc. 2014, 136, 5904-5907;
g) C. Suzuki, K. Hirano, T. Satoh, M. Miura, Org. Lett. 2015, 17,
2
013, 135, 10630-10633; e) Y. Lian, J. R. Hummel, R. G. Bergman,
J. A. Ellman, J. Am. Chem. Soc. 2013, 135, 12548-12551; f) K.
Nobushige, K. Hirano, T. Satoh, M. Miura, Org. Lett. 2014, 16,
1
597-1600; h) K. Shin, S. W. Park, S. Chang, J. Am. Chem. Soc.
015 137, 8584-8592; i) Y. Kim, J. Park, S. Chang, Org.
1
188-1191; g) D. G. Yu, F. de Azambuja, F. Glorius, Angew. Chem.,
2
,
Int. Ed. 2014, 53, 2754-2758; h) J. Jayakumar, K. Parthasarathy, Y.
H. Chen, T. H. Lee, S. C. Chuang, C. H. Cheng, Angew. Chem., Int.
Ed. 2014, 53, 9889-9892.
Lett. 2016, 18, 1892-1895; j) P. Gao, W. Guo, J. Xue, Y. Zhao, Y.
Yuan, Y. Xia, Z. Shi, J. Am. Chem. Soc. 2015, 137, 12231-12240; k)
T. Zhou, L. Li, B. Li, H. Song, B. Wang, Org. Lett. 2015, 17, 4204-
[
4]
a) G. Liu, Y. Shen, Z. Zhou, X. Lu, Angew. Chem., Int. Ed. 2013, 52,
4
207; l) Y. Xia, Z. Liu, S. Feng, Y. Zhang, J. Wang, J. Org. Chem.
015, 80, 223-226; m) L. Huang, D. Hackenberger, L. J. Gooßen,
6
033-6037; b) B. Liu, C. Song, C. Sun, S. Zhou, J. Zhu, J. Am.
2
Chem. Soc. 2013, 135, 16625-16631; c) C. Wang, Sun, Y. Fang, Y.
Huang, Angew. Chem., Int. Ed. 2013, 52, 5795-5798; d) U. Sharma,
Y. Park, S. Chang, J. Org. Chem. 2014, 79, 9899-9906; e) D. Zhao,
F. Lied, F. Glorius, Chem. Sci. 2014, 5, 2869-2873; f) J. M. Neely, T.
Rovis, J. Am. Chem. Soc. 2014, 136, 2735-2738; g) Y. Chen, D.
Wang, P. Duan, R. Ben, L. Dai, X. Shao, M. Hong, J. Zhao, Y.
Huang, Nat. Commun. 2014, 5, 4610-4618; h) F. Hu, Y. Xia, F. Ye,
Z. Liu, C. Ma, Y. Zhang, J. Wang, Angew. Chem., Int. Ed. 2014, 53,
Angew. Chem., Int. Ed. 2015, 54, 12607-12611; n) Y. Wu, Y.
Yang, B. Zhou, Y. Li, J. Org. Chem. 2015, 80, 1946-1951; o) H.
Wang, F. Xie, Z. Qi, X. Li, Org. Lett. 2015, 17, 920-923; p) J. Zhou,
J. Shi, Z. Qi, X. Li, H. E. Xu, W. Yi, ACS Catal. 2015, 5, 6999-7003;
q) R. S. Phatake, P. Patel, C. V. Ramana, Org. Lett. 2016, 18, 292-
2
5
5
3
95; r) H. Kim, G. Park, J. Park, S. Chang, ACS Catal. 2016, 6,
922-5929; s) X. Yang, J. Jie, H. Li, M. Piao, RSC Adv. 2016, 6,
7371-57374; t) Y. Li, F. wang, S. Yu, X. Li, Adv. Synth. Catal. 2016
58, 880-886.
,
1
364-1367; i) Y. J. Liu, H. Xu, W. J. Kong, M. Shang, H. X. Dai, J.
This article is protected by copyright. All rights reserved

European Journal of Organic Chemistry
10.1002/ejoc.201601212
COMMUNICATION
[
11] a) J. Shi, G. Zhao, X. Wang, H. E. Xu, W. Yi, Org. Biomol. Chem.
014, 12, 6831-6836; b) B. Gong, J. Shi, X. Wang, Y. Yan, Q. Li, Y.
Giampietro, R. Amoroso, ChemMedChem 2013, 8, 1609-1616; d) S.
2
Garcia-Vallvé, L. Guasch, S. Tomas-Hernández, J. M. del Bas, V.
Meng, H. E. Xu, W. Yi, Adv. Synth. Catal. 2014, 356, 137-143; c) J.
Jia, J. Shi, J. Zhou, X. Liu, Y. Song, H. E. Xu, W. Yi, Chem.
Commun. 2015, 51, 2925-2928.
Ollendorff, L. Arola, G. Pujadas, M. Mulero, J. Med. Chem. 2015
58 5381-5394
,
,
.
[13] C. Pan, N. Jin, H. Zhang, J. Han, C. Zhu, J. Org. Chem. 2014, 79,
9427-9432.
[
12]
For selected examples, see: a) Y. Lamotte, P. Martres, N. Faucher,
A. Laroze, D. Grillot, N. Ancellin, Y. Saintillan, V. Beneton, R. T.
Gampe Jr., Bioorg. Med. Chem. Lett. 2010, 20, 1399-1404; (b) J. H.
Choi, A. S. Banks, T. M. Kamenecka, S. A. Busby, M. J. Chalmers,
N. Kumar, D. S. Kuruvilla, Y. Shin, Y. He, J. B. Bruning, D. P.
Marciano, M. D. Cameron, D. Laznik, M. J. Jurczak, S. C. Schurer,
D. Vidovic, G. I. Shulman, B. M. Spiegelman, P. R. Griffin, Nature
[14] a) J. Oxgaard, W. J. Tenn, R. J. Nielsen, R. A. Periana, W. A.
Goddard, Organometallics 2007, 26, 1565-1567; b) L. Ackermann,
Chem. Rev. 2011, 111, 1315-1345; c) W. Ma, R. Mei, G. Tenti, L.
Ackermann, Chem.-Eur. J. 2014, 20, 15248-15251.
[15] J. Shi, J. Zhou, Y. Yan, J. Jia, X. Lei, S. Song, H. E. Xu, W. Yi,
Chem. Commun. 2015, 51, 668-671.
2
011, 477, 477-481; c) A. Ammazzalorso, B. De Filippis, L.
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A novel and simple protocol via Ir(III)-
catalyzed carbenoid insertion C−H
alkylation mediated by α-diazotized
Meldrum’s acid has been developed.
C−H alkylation
H. Lv, W. L. Xu, K. Lin, J. Shi* and W.
Yi*
Page No. – Page No.
Ir(III)-catalyzed
Regioselective
Carbenoid Insertion C−H Alkylation
by α-diazotized Meldrum’s Acid
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