Rh(iii)-catalyzed and alcohol-involved carbenoid C-H insertion into N-phenoxyacetamides using α-diazomalonates

Article abstract of DOI:10.1039/c5cc00354g

Here we report a new and mild Rh(iii)-catalyzed and alcohol-involved carbenoid C-H insertion into N-phenoxyacetamides using α-diazomalonates. This reaction provided a straightforward way for installing both an α-quaternary carbon center and a free-OH moiety into the phenyl ring, thus giving access to useful 2-(2-hydroxyphenyl)-2-alkoxymalonates with good substrate/functional group tolerance. This journal is

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COMMUNICATION
Rh(III)-catalyzed and alcohol-involved carbenoid C–H insertion of N-
phenoxyacetamides by α-diazomalonates
Jie Zhou, a,b Jingjing Shi,b Xuelei Liu,b Jinlong Jia,b Huacan Song, a H. Eric Xu*b,c and Wei Yi*b
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
5
DOI: 10.1039/b000000x
50 herein describe a new and mild Rh(III)-catalyzed carbenoid C–H
insertion (ortho-alkylation) of diverse N-phenoxyacetamides by
α-diazomalonates for direct synthesis of 2-(2-hydroxyphenyl)-2-
alkoxymalonates, in which O–NHAc group was used as the ODG
((eqn (1)). Notably, in this reaction, alcohol also employed as the
55 reagents to mediate the alcoholysis of intermediate F via a similar
1,4-addition pathway, thereby installing both α-quaternary carbon
center and free-OH moiety into the phenyl ring, which was very
different from the reported reactions of Rh(III)-catalyzed
carbenoid insertion.3k,l,7
Here we report a new and mild Rh(III)-catalyzed and
alcohol-involved carbenoid C–H insertion of N-
phenoxyacetamides by α-diazomalonates. This reaction
provided a straightforward way for installing both α-
10 quaternary carbon center and free-OH moiety into the phenyl
rings, thus giving access to privileged 2-(2-hydroxyphenyl)-2-
alkoxymalonates with good substrate/functional group
tolerance.
60
Transition-metal-catalyzed functionalization of inert C–H
15 bonds has emerged as one of the most popular and powerful tools
for step- and atom-economical construction of diversified
complex molecules, and to date, significant progress has been
made in this hot area of research.1 In general, to achieve the
efficient C–H functionalization, the use of a combination of
20 directing groups (DGs) and stoichiometric or excess amounts of
external oxidants is commonly required. Indeed, they could
improve the regioselectivity as well as reaction efficiency of the
C–H activation reactions. However, in spite of the success, this
strategy also presents two main disadvantages: (1) the
25 introduction of DGs often leaves a chemical trace in the products,
limiting their structural diversity; (2) the compulsive use of
external oxidants involves relatively harsh reaction conditions
and produces stoichiometric amounts of related metal wastes.
To address aforementioned drawbacks, recently one emerging
30 strategy to develop an innovative oxidizing-directing group
(ODG) which acts simultaneously as both DG and internal
oxidant has attracted much attention.2 As a consequence,
remarkable advances has been made and several versatile ODGs
such as N–OR,3 N–NR4 and O–NHAc5 are stood out.
Table 1 Optimization Studiesa
O
OH
O
COOEt
cat. [Rh (III)]
CH3OH, RT
N
OCH3
N2
H
COOEt
COOEt
COOEt
2a
H
1a
3a
Entry
Catalyst system (mol %)
Solvent (mL)
Yieldb (%)
1
2
[Cp*RhIII(MeCN)3](SbF6)2 (5)
[Cp*RhIII(MeCN)3](SbF6)2 (2.5)
[Cp*RhIII(MeCN)3](SbF6)2 (1)
[Cp*RhIII(MeCN)3](SbF6)2 (2.5)
[Cp*RhIII(MeCN)3](SbF6)2 (0)
[Cp*RhCl2]2 (2.5)/AgSbF6 (100)
[Cp*Rh(OAc)2]2
CH3OH (1.0)
CH3OH (1.0)
CH3OH (1.0)
CH3OH (0.5)
CH3OH (1.0)
CH3OH (1.0)
CH3OH (1.0)
CH3OH (1.0)
83
81
45
70
0
3
4
5
6
58
0
7
8c
[Cp*RhIII(MeCN)3](SbF6)2 (2.5)
78
aReaction conditions: 1a (0.10 mmol, 1.0 equiv), 2a (0.12 mmol, 1.2 equiv), Rh catalyst (X
mol%), solvent (0.5 or 1.0 mL), 10 h, under air. bIsolated yields. c Performed on a 2.0
65 mmol scale.
Given the successful history of [Cp*Rh(MeCN)3](SbF6)2 in the
field of C–H activation,8 therefore, at the outset of this study, we
chose it as the Rh(III) catalyst for the reaction development with
70 N-phenoxyacetamide 1a as the model substrate and MeOH as the
solvent (Table 1). To our surprise, a preliminary survey of diazo
compounds9 showed that the reaction of 1a with diethyl 2-
diazomalonate 2a at room temperature for 10 h proceeded
successfully to deliver the free-OH-substituted alkylation product
75 3a in 83% yield (entry 1), in which O–NHAc group was used as
the ODG5 and MeOH was used not only as the solvent but also as
the reagent in the catalytic reaction, thereby leading to installing a
α-quaternary carbon center into the ortho-position of hydroxy
group. Encouraged by this finding, we next investigated the
80 effects of catalyst loading and concentration for this reaction
optimization. Reducing the loading of catalyst from 5 mol% to
2.5 mol% resulted in the isolation of 3a in 81% yield (entry 2).
However, further reducing the loading of catalyst to 1 mol% led
to a significant decrease in the product yield (45% yield, entry 3).
85 Similarly, decreasing the amount of MeOH also gave lower
conversion (entry 4). As predicted, no desired product was
35
On the other hand, recently diazo compounds have been widely
used as powerful cross-coupling partners for transition-metal-
catalyzed direct C–H functionalization, of which Rh catalysts
plays a particularly prominent role.6,7 For example, inspired by
the pioneering work of Yu,7a afterwards the groups of Rovis,3k
40 Glorius,7b Li,7c,d Cui,3l,7e Yu,7f Wang,7g,h Chang,7i Zhou,7j
Cramer,7k Liu7l and our groups7m,n have displayed the successful
exploration of diazo compounds as the cross-coupling partners in
Rh(III)-catalyzed C–H functionalization with a DG-assisted
strategy.
45
This works:
O
O
OH
O
Cp*
COOR2
COOR1
O
H
cat. Rh (III)
RT
ROH
N
Rh
COOR1
COOR2
N2
(1)
R
H
COOEt
COOEt
F
A new and mild Rh(III)-catalyzed and alcohol-involved carbenoid insertion C-H functionalization
Taking advantage of above information and in continuation of
our interest in the Rh(III)-catalyzed C–H functionalization, we
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DOI: 10.1039/C5CC00P35a4gGe 2 of 4
formed in the absence of catalyst (entry 5). Finally, change of 40 attached at the less-hindered site. Conjunctively, meta-methoxyl-
catalyst [Cp*Rh(MeCN)3](SbF6)2 to other well-known Rh(III)
catalysts such as [Cp*RhCl2]2 and [Cp*Rh(OAc)2]2 inhibited the
process (entries 6-7). In summary, the optimal conditions were
identified as the following: 2.5 mol% [Cp*Rh(MeCN)3](SbF6)2 in
substituted N-phenoxyacetamide 1i gave a 3:1 mixture of
products 3i (i) and 3i (ii). Taken together, these results revealed
that the type of the substituent at the meta-position played a key
role in determining the reaction process. Moreover, polyaromatic
5
1.0 mL of MeOH at room temperature for 10 h under an 45 diphenyl substrate could be accommodated in the catalytic system,
atmosphere of air. Finally, the reaction could be performed on a
2.0 mmol scale under the optimized conditions with decent
isolated yield (78%, entry 8).
giving the desired product 3l in reasonably good yield (82%).
Notably, the alkylation reaction with 2a also tolerated the alkenyl
substrate, which produced the interesting furanone 3n in 55%
yield with a stereogenic α-carbon center. In addition, tert-butyl
50 diazomalonates 2b-c was also investigated in the Rh(III) system.
As shown in Scheme 1, 2b-c coupled efficiently with N-
phenoxyacetamides to offer the corresponding ortho-alkylation
product 3n-p in synthetically useful yields (78% for 3n, 72% for
3o and 70% for 3p), where tert-butyl moiety was retained
55 perfectly. The results further illustrated the remarkable robustness
of our developed Rh(III) catalysis.
10
O
OH
[Cp*Rh(MeCN)3][SbF6]2
(2.5 mol%)
O
H
COOR1
R
N
OCH3
COOR1
COOR2
R
N2
H
CH3OH, 10 h, RT
COOR2
2
1
3
OH
OH
OH
OCH3
OCH3
OCH3
COOEt
COOEt
3d, 75%
H3C
H3CO
H3C
Br
COOEt
COOEt
COOEt
COOEt
3b, 78%
3c, 83%
O
OH
O
[Cp*Rh(MeCN)3][SbF6]2
(2.5 mol%)
O
H
OH
OH
F3C
OH
OCH3
COOEt
R
N
N2
H
OCH3
OCH3
COOEt
COOEt
3f, 73%
COOEt
COOEt
ROH, 10 h, RT
COOEt
2 a
MeOOC
COOEt
COOEt
COOEt
COOEt
3g, 58%
1a
3
3e, 66%
OH
O
OH
O
OH D
O
OH
O
D
D
COOEt
OH
COOEt
OH
MeO
OH
EtOOC
MeO
EtOOC
F
COOEt
COOEt
3r, 51%a
COOEt
COOEt
3s, 57%a
COOEt
COOEt
COOEt
COOEt
3q, 64%a
OCH3
COOEt
COOEt
OCH3
COOEt
COOEt
OCH3
COOEt
3t, 76%
3i, 73%
3:1, 3i (i):3i (ii)a
COOEt
(ii)
(i)
Br
3h, 61%
Cl
Scheme 2 Scope of alcohols. Reaction conditions: 1 (0.10 mmol) and 2 (0.12
60 mmol) in the corresponding alcohol (1.0 mL) at room temperature for 10 h
under air. Isolated yields. aThese reactions ran at 80 oC.
OH
OH
OH
OCH3
OCH3
OCH3
COOEt
COOEt
COOEt
COOEt
COOEt
3k, 72%
Since methanol has played dual roles as both reactant and
reaction medium in this reaction (as shown above), subsequently
65 several alkyl alcohols were evaluated in the current catalytic
system (Scheme 2). As expected, the reactions occurred
successfully under air to give the corresponding ortho-alkylated
products 3q-3s in 64%, 51% and 57% yields, respectively. Of
note, the reaction also worked well in CD3OD to afford the
70 methyl-deuterated 3t in good isolated yield (76%), which
provided hints of the reaction mechanism.
COOEt
3l, 82%
3j, 78%
OH
OH
OCH3
OH
O
O
OCH3
OCH3
Br
COOEt
COOt-Bu
COOEt
COOt-Bu
3n, 78%
COOt-Bu
COOt-Bu
H3CO
COOt-Bu
3p, 70%
3m, 55%
3o, 72%
Scheme 1 Scope of N-phenoxyacetamides. Reaction conditions: 1 (0.10
mmol) and 2 (0.12 mmol) in MeOH (1.0 mL) at room temperature for 10 h
under air. Isolated yields. aThe ratio was determined by isolated yields.
Inspired by the above results and to obtain better insight into
the reaction mechanism, a set of additional experiments were
carried out (Scheme 3). First, 1a was treated with
75 [Cp*Rh(MeCN)3](SbF6)2 in CD3OD (Scheme 3a) in the absence
of diazomalonates. After stirring at room temperature for 3 h, 98%
of 1a was recovered and no deuterium incorporation was
observed, revealing that the C–H bond activation step was largely
irreversible. Next, the isotope-labeling experiment was conducted
80 with a deuterium-labeled N-phenoxyacetamide [D5]-1a. As
demonstrated in Scheme 3b, treatment of 2a with the same
amounts of both 1a and [D5]-1a for 30 min under standard
conditions gave a relatively large KIE value (kH/kD = 2.7). The
result suggested that C–H bond-cleavage process might be
85 involved in the rate-limiting step. Subsequently, the competition
experiment of equimolar amounts of 1f and 1g under the standrad
reaction conditions with 2a was carried out to to delineate the
action mode of the reaction (Scheme 3c). The ratio of products
showed that electron-deficient 1g was preferentially converted
90 (3f/3g = 1:10), revealing that the C-H activation might be via a
concerted-metallation-deprotonation (CMD) mechanism.3k,10
Moreover, N-methyl-substituted phenoxyacetamide 1o was
prepared and was designated as a substrate to evaluate the role of
N–H bond (Scheme 3d). As expected, the reaction of 1o and 2a
95 did not proceed, indicating that the N–H bond of O–NHAc was
indispensable for this transformation, which is consistent with
15
With this efficient catalytic system established, we sought to
explore the scope of substrates and generality of this reaction. As
shown in Scheme 1, diazomalonate 2a efficiently coupled with a
variety of substituted N-phenoxyacetamides in MeOH to provide
20 the corresponding 2-(2-hydroxyphenyl)-2-alkoxymalonates in
moderate to good yields. Substitutions at the para- (3b-e and 3l),
meta- (3f-i), or ortho- (3j-k) postion were all well tolerated.
Importantly, the reaction also showed good compatibility with a
wide range of valuable functional groups such as methyl,
25 methoxy, bromo chloro, fluoro, ester, and trifluoromethyl
substituents. Tolerance to the chloro (3j), bromo (3d, 3k and 3p),
and ester (3e) functional groups was especially noteworthy since
they could be used as versatile building-blocks for further
synthetic transformations. The electronic nature of the
30 substituents on the benzene ring of substrates 1 had no obvious
influence on the reaction outcome, and in the present cases, N-
phenoxyacetamides bearing both electron-donating and
-
withdrawing groups showed excellent reaction efficiency.
Interestingly, substrates 1f and 1g bearing methyl and
35 terfluoromethyl groups at meta-position, respectively, provided
the corresponding products in moderate yields with exclusive
regioselectivity. However, meta-fluoro-substituted derivative 1h
afforded the dialkylated product in 61% yield, where an
additional substituent (1,3-diethoxy-1,3-dioxopropan-2-yl) was
2
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previous report by Lu and co-workers.5b Finally, an experiment
using 2a as the sole substrate in MeOH was performed under 35 could undergo an esterlysis/decarboxylation in the presence of
synthetic manipulations. As illustrated in Scheme 5, product 3a
otherwise identical conditions. As demonstrated in Scheme 3e,
the diethyl 2-methoxymalonate 4a was not detected, providing
clear evidence that MeOH was not involved in the classic metal-
carbene insertion into C(sp3)−H bond mechanism.11
LiOH to give the valuable ethyl 2-hydroxy-α-methoxy-
benzenacetate 5a. In addition, product 3a also could produce the
important 6a through a standrad intramolecular-transesterification.
Further transformation of 6a via an esterlysis/decarboxylation
40 process yielded the 3-substituted benzofuran-2(3H)-one 7a, a
very valuable skeleton in natural products and biologically active
compounds.12
5
a)
H
O
H/D
O
[Cp*Rh(MeCN)3][SbF6]2 (2.5 mol%)
CD3OD, 3 h, RT
O
H
O
N
H
N
OH
OH
H
LiOH
H/D
OCH3
COOEt
COOEt
OMe
MeOH/H20
1a
H
98% recovery, <5% D
5a
3a
COOH
b)
H
O
D
O
TsOH
Toluene
Standard conditions
O
H
D
D
O
D
OH
N
H
N
30 min
H
H4/D4
O
O
OCH3
COOEt
KIE =2.7
COOEt
COOEt
O
O
H
LiOH
N2
2a
H
1a
D
COOEt
MeOH/H20
[D5]-1a
COOEt
MeO
6a
7a
OMe
c)
Scheme 5 Derivatization of 3a.
O
O
Me/F3C
OH
45
Standard conditions
F3C
O
Me
O
60 min
N
N
In summary, we have developed the first example of Rh(III)-
catalyzed and alcohol-involved carbenoid C–H insertion (ortho-
alkylation) of N-phenoxyacetamides by α-diazomalonates for
direct and highly efficient synthesis of privileged 2-(2-
OCH3
COOEt
COOEt
H
H
COOEt
N2
2a
Me:CF3= 1:10
1g
1f
COOEt
d)
O
50 hydroxyphenyl)-2-alkoxymalonates with a α-quaternary carbon
center and free-OH moiety, in which O–NHAc group was
employed as the versatile ODG. Considering the valuable
structures of the products, mild reaction conditions, and good
substrate/functional group tolerance, the reaction should have
55 potential of wide synthetic utility.
We thank Shanghai Municipal Natural Science
Foundation (15ZR1447800), China and the Chinese Postdoctoral
Science Foundation (2012M511158, 2013T60477 and
2014M560363) for financial support on this study.
O
H
COOEt
[Cp*Rh(MeCN)3][SbF6]2 (2.5 mol%)
CH3OH, 10 h, RT
N
N2
No reaction
CH3
COOEt
2a
1o
e)
COOEt
COOEt
[Cp*Rh(MeCN)3][SbF6]2 (2.5 mol%)
CH3OH, 10 h, RT
COOEt
COOEt
N2
2a
MeO
4a
Scheme 3 Mechanistic experiments.
10
Taking the above observations and the mechanism studies of
precedent literature into consideration, a plausible reaction
mechanism is proposed in Scheme 4. First, the coordination of N-
phenoxyacetamide 1a to a [Cp*Rh(III)] species was the key rate-
15 determining step for the regioselective C−H bond cleavage to
form a five-membered rhodacyclic intermediate A. Further
coordination of A with 2a afforded the diazonium intermediate B.
60 Notes and references
aSchool of Chemistry and Chemical Engineering, Sun Yat-sen University,
Guangzhou 510275, P.R. China
bVARI/SIMM Center, Center for Structure and Function of Drug Targets,
CAS-Key Laboratory of Receptor Research, Shanghai Institute of
65 Materia Medica, Chinese Academy of Sciences, Shanghai 201203, P.R.
China.
Subsequently, Rh(III)–carbene migratory insertion from
B
provided six-membered rhodacycle intermediate C with the
20 emission of N2. Protonolysis of C delivered the intermediate D
via the Rh−N bond cleavage. Subsequently, the intramolecular
coordination of intermediate D was occured to form intermediate
E, followed by α-H elimination/intramolecular rearrangement to
afford intermediate F with extrusion of acetamide. Finally,
25 intermediate F underwent a similar 1,4-addition step by using
MeOH as reactant to give the desired product 3a along with the
regeneration of the rhodium(III) catalyst.
cLaboratory of Structural Sciences, Program on Structural Biology and
Drug Discovery, Van Andel Research Institute, Grand Rapids, Michigan
49503, USA
70 E-mail: yiwei.simm@simm.ac.cn and eric.xu@simm.ac.cn
†Electronic Supplementary Information (ESI) available: Detailed
experimental procedure and characterization data of all new compounds.
See DOI: 10.1039/b000000x/
1
For selected reviews, see: (a) G. Song, F. Wang and X. Li, Chem.
Soc. Rev., 2012, 41, 3651; (b) D. A. Colby, A. S. Tsai, R. G.
Bergman and J. A. Ellman, Acc. Chem. Res., 2012, 45, 814; (c) C.
Zhu, R. Wang and J. R. Falck, Chem. –Asian J., 2012, 7, 1502; (d)
N. Kuhl, M. N. Hopkinson, J. Wencel-Delord and F. Glorius, Angew.
Chem., Int. Ed., 2012, 51, 10236; (e) S. R. Neufeldt and M. S.
Sanford, Acc. Chem. Res., 2012, 45, 936; (f) S. I. Kozhushkov and L.
Ackermann, Chem. Sci., 2013, 4, 886; (g) J. Wencel-Delord and F.
Glorius, Nat. Chem., 2013, 5, 369; (h) V. S. Thirunavukkarasu, S. I.
Kozhushkov and L. Ackermann, Chem. Commun., 2014, 50, 29; (i)
L. Ackermann, Acc. Chem. Res., 2014, 47, 281; (j) N. Kuhl, N.
Schröder and F. Glorius, Adv. Synth. Catal., 2014, 356, 1443; (k) Y.
Zhang, X. Jie, H. Zhao, G. Li and W. Su, Org. Chem. Front., 2014,
1, 843; (l) C. X. Zhuo, C. Zheng and S. L. You, Acc. Chem. Res.,
2014, 47, 2558; (m) F. Chen, T. Wang and N. Jiao, Chem. Rev.,
2014, 114, 8613; (n) R. He, Z. T. Huang, Q. Y. Zheng, C. Wang,
Tetrahedron Lett., 2014, 55, 5705.
75
80
85
90
O
Cp*
Cp*
Rh
Ac
O
O
H2NAc
HN
NH
Cp*
Rh
O
COOEt
Rh
COOEt
COOEt
H+
OH
COOEt
E
COOEt
D
CH3OH
COOEt
F
OCH3
COOEt
COOEt
3a
H+
Cp*
Rh
Ac
O
O
N
Ac
2a
1a
O
N
COOEt
[Cp*Rh(III)]
N Ac
Rh
Rh
Cp*
2H+
COOEt
C
EtOOC
N
N
Cp*
COOEt
B
A
30 Scheme 4 Proposed mechanism.
Importantly,
the
obtained
2-(2-hydroxyphenyl)-2-
2
F. W. Patureau and F. Glorius, Angew. Chem., Int. Ed., 2011, 50,
1977.
alkoxymalonates could serve as useful platforms for further
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DOI: 10.1039/C5CC00P35a4gGe 4 of 4
3
For selected examples on C–H activation by using N–OR groups as
N. Cramer, Angew. Chem., Int. Ed., 2014, 53, 7896; (l)X. G. Li, M.
Sun, K. Liu, Q. Jin and P. N. Liu, Chem. Commun., 2015, DOI:
ODGs, see: (a) J. Wu, X. Cui, L. Chen, G. Jiang and Y. Wu, J. Am.
Chem. Soc., 2009, 131, 13888; (b) S. Rakshit, C. Grohmann, T.
Besset and F. Glorius, J. Am. Chem. Soc., 2011, 133, 2350; (c) T. K.
Hyster and T. Rovis, Chem. Commun., 2011, 47, 11846; (d) X.
Zhang, D. Chen, M. Zhao, J.Zhao, A. Jia and X. Li, Adv. Synth.
Catal., 2011, 353, 719; (e) N. Guimond, S. I. Gorelsky and K.
Fagnou, J. Am. Chem. Soc., 2011, 133, 6449; (f) C. Kornhaaβ, J. Li
and L. Ackermann, J. Org. Chem., 2012, 77, 9190; (g) H. Wang and
F. Glorius, Angew. Chem., Int. Ed., 2012, 51, 7318; (h) T. K. Hyster,
K L. Knörr, T. R. Ward and T. Rovis, Science, 2012, 338, 500; (i) H.
Wang, C. Grohmann, C. Nimphius and F. Glorius, J. Am. Chem.
Soc., 2012, 134, 19592; (j) B. Ye and N. Cramer, Science, 2012, 338,
504; (k) T. K. Hyster, K. E. Ruhl and T. Rovis, J. Am. Chem. Soc.,
2013, 135, 5364; (l) S. Cui, Y. Zhang, D. Wang and Q. Wu, Chem.
Sci., 2013, 4, 3912; (m) X. Huang, J. Huang, C. Du,; X. Zhang, F.
Song and J. You, Angew. Chem., Int. Ed., 2013, 52, 12970; (n) U.
Sharma, Y. Park and S. Chang, J. Org. Chem., 2014, 79, 9899; (o)
D. Zhao, F. Lied and F. Glorius, Chem. Sci., 2014, 5, 2869; (p) D. G.
Yu, F. de Azambuja, T. Gensch, C. G. Daniliuc and F. Glorius,
Angew. Chem., Int. Ed., 2014, 53, 9650; (q) X. Zhang, Z. Qi and X.
Li, Angew. Chem., Int. Ed., 2014, 53, 10794; (r) J. M. Neely and T.
Rovis, J. Am. Chem. Soc., 2014, 136, 2735; (s) Y. J. Liu, H. Xu. W.
J. Kong, M. Shang, H. X. Dai and J. Q. Yu, Nature, 2014, 515, 389.
For selected examples on C–H activation by using N–NR groups as
ODGs, see: (a) D. Zhao, Z. Shi and F. Glorius, Angew. Chem., Int.
Ed., 2013, 52, 12426; (b) C. Wang and Y. Huang, Org. Lett., 2013, 100
15, 5294; (c) B. Liu, C. Song, C. Sun, S. Zhou and J. Zhu, J. Am.
Chem. Soc., 2013, 135, 16625; (d) C. Wang, H. Sun, Y. Fang and Y.
Huang, Angew. Chem., Int. Ed., 2013, 52, 5795; (e) L. Zheng and R.
Hua, Chem. −Eur. J., 2014, 20, 2352; (f) K. Muralirajan, C. H.
Cheng, Adv. Synth. Catal., 2014, 356, 1571; (g) T. Matsuda and Y.
Tomaru, Tetrahedron Lett., 2014, 55, 3302; (h) Z. Zhang, H. Jiang
and Y. Huang, Org. Lett., 2014, 16, 5976; (i) H. Sun, C.Wang, Y. F.
Yang, P. Chen, Y. D. Wu, X. Zhang and Y. Huang, J. Org. Chem.,
2014, 79, 11863; (j) B. Zhou, J. Du, Y.Yang and Y. Li, Chem. −Eur.
J., 2014, 20, 12768; (k) B. Zhou, Y. Yang, H. Tang, J. Du, H. Feng
and Y. Li, Org. Lett., 2014, 16, 3900.
75
10.1039/c4cc09314c; (m) J. Shi, Y. Yan, Q. Li, H. E. Xu and W. Yi,
Chem. Commun., 2014, 50, 6483; (n) J. Shi, J. Zhou, Y. Yan, J. Jia,
X. Liu, H, Song, H. E. Xu and W. Yi, Chem. Commun., 2015, 51,
668.
5
10
15
20
80 8
For the representative examples, see: (a) N. Guimond and K.
Fagnou, J. Am. Chem. Soc., 2009, 131, 12050; (b) D. R. Stuart, P.
Alsabeh, M. Kuhn and K. Fagnou, J. Am. Chem. Soc., 2010, 132,
18326; (c) D. J. Schipper, M. Hutchinson and K. Fagnou, J. Am.
Chem. Soc., 2010, 132, 6910; (d) M. P. Huestis, L. Chan, D. R.
Stuart and K. Fagnou, Angew. Chem., Int. Ed., 2011, 50, 1338; (e) J.
Shi, B. Zhou, Y. Yang and Y. Li, Org. Biomol. Chem., 2012, 10,
8953; (f) W. Zhen, F. Wang, M. Zhao, Z. Du and X. Li, Angew.
Chem. Int. Ed., 2012, 51, 11819; (g) Y. Chen, F. Wang, W. Zhen, X.
Li, Adv. Synth. Catal., 2013, 355, 353; (h) D. S. Kim, J. W. Park and
C. H. Jun, Adv. Synth. Catal., 2013, 355, 2667; (i) T. Gong, B. Xiao,
W. Cheng, W. Su, J. Xu, Z. Liu, L. Liu and Y. Fu, J. Am. Chem.
Soc., 2013, 135, 10630; (j) Y. Lian, J. R. Hummel, R. G. Bergman, J.
A. Ellman, J. Am. Chem. Soc., 2013, 135, 12548; (k) K. Nobushige,
K. Hirano, T. Satoh and M. Miura, Org. Lett., 2014, 16, 1188; (l) D.
G. Yu, F. de Azambuja and F. Glorius, Angew. Chem., Int. Ed.,
2014, 53, 2754.
85
90
95
9
Ethyl diazoacetoacetate and methyl 2-diazo-2-phenylacetate were
also tested. The results showed that the reaction of ethyl
diazoacetoacetate or methyl 2-diazo-2-phenylacetate and MeOH
was occurred to give ethyl 2-methoxy-3-oxobutanoate (trace) and
25 4
methyl 2-methoxy-2-phenylacetate
(58% isolated yield),
respectively, where substrate 1a was retained perfectly with over 95%
30
recovery rate.
OMe
N2
Me
O
Me
COOEt
(trace)
COOEt
[Cp*Rh(MeCN)3][SbF6]2
(5 mol%)
O
H
O
(0.12 mmol)
N
O
H
or
OMe
or
MeOH, 10 h, RT
N2
1a
35
COOMe
(58% yield)
(0.10 mmol)
COOMe
(0.12 mmol)
>95% recovery of 1a
105 10 For selected rhodium involved cleavage of aromatic C–H bonds
through CMD way, see: (a) T. K. Hyster and T. Rovis, J. Am. Chem.
Soc., 2010, 132, 10565; (b) L. Ackermann, Chem. Rev., 2011, 111,
1315; (c) H. Wang and F. Glorius, Angew. Chem., Int. Ed., 2012, 51,
7318; (d) J. Zheng and S. L. You, Chem. Commun., 2014, 50, 8204.
110 11 (a) K. B. Eisenthal, N. J. Turro, E. V. Sitzmann, I. R. Gould, G.
Hefferon, J. Langan and Y. Cha, Tetrahedron, 1985, 41, 1543; (b) D.
A. Modarelli, S. Morgan and M. S. Platz, J. Am. Chem.
Soc., 1992, 114, 7034; (c) V. V. Shevchenko, N. G. Zhegalova, A. O.
Borzenko and V. A. Nikolaev, Helv. Chem. Acta, 2008, 91, 501. (d)
W. S. Jenks, M. J. Heying and E. M. Rockafellow, Org. Lett., 2009,
11, 955; (e) P. J. Davis, L. Harris, A. Karim, A. L. Thompson, M.
Gilpin, M. G. Moloney, M. J. Pound and C. Thompson, Tetrahedron
Lett., 2011, 52, 1553.
5
For selected examples on C–H activation by using O–NAc group as
a ODG, see: (a) G. Liu, Y. Shen, Z. Zhou and X. Lu, Angew. Chem.,
Int. Ed., 2013, 52, 6033; (b) Y. Shen, G. Liu, Z. Zhou and X. Lu,
Org. Lett., 2013, 15, 3366; (c) F. Hu, Y. Xia, F. Ye, Z. Liu, C. Ma,
Y. Zhang and J. Wang, Angew. Chem., 2014, 126, 1388; (d) H.
Zhang, K. Wang, B. Wang, H. Yi, F. Hu, C. Li, Y. Zhang and J.
Wang, Angew. Chem., Int. Ed., 2014, 53, 13234; (e) P. Duan, X.
Lan, Y. Chen, S. S. Qian, J. J. Li, L. Lu, Y. Lu, B. Chen, M. Hong
and J. Zhao, Chem. Commun., 2014, 50, 12135; (f) Y. Chen, D.
Wang, P. Duan, R. Ben, L. Dai, X. Shao, M. Hong, J. Zhao and Y.
Huang, Nat. Commun., 2014, 5, 4610.
For selected reviews, see: (a) Z. Zhang and J. Wang, Tetrahedron,
2008, 64, 6577; (b) H. M. L. Davies and J. R. Manning, Nature,
2008, 451, 417; (c) M. P. Doyle, R. Duffy, M. Ratnikov, L. Zhou,
40
45
115
50 6
12 (a) A. Closse, W. Haefliger and D. Hauser, J. Med. Chem., 1981, 24,
1465; (b) W. D. Inman, J. Luo, S. D. Jolad, S.R. King and R.
Cooper, J. Nat. Prod., 1999, 62, 1088; (c) M. L. Garduño-Ramírez,
A. Trejo, V. Navarro, R. Bye, E. Linares and G. Delgado, J. Nat.
Prod., 2001, 64, 432; (d) G. D. Huang, Y. J. Yang, W. S. Wu and Y.
Zhu, J. Nat. Prod., 2010, 73, 1954; (e) L. J. Wang, J. Xiong, S. T.
Liu and J. F. Hu, Chem. Biodivers., 2014, 11, 919.
Chem. Rev. 2010, 110, 704; (d) Y. Zhang and J. Wang, Eur. J. Org.
120
Chem. 2011, 1015; (e) J. Barluenga and C. Valdés, Angew. Chem.,
Int. Ed., 2011, 50, 7486; (f) Z. Shao and H. Zhang, Chem. Soc. Rev.,
2012, 41, 560; (g) Q. Xiao, Y. Zhang and J. Wang, Acc. Chem. Res.,
2013, 46, 236; (h) Z. Liu and J. Wang, J. Org. Chem., 2013, 78,
55
10024; (i) Y. Xia, Y. Zhang and J. Wang, ACS Catal., 2013, 3, 2586.
125
7
For representative examples on Rh(III)-catalyzed carbenoid C–H
insertion reactions, see: (a) W. W. Chan, S. F. Lo, Z. Zhou and W.
Y. Yu, J. Am. Chem. Soc. 2012, 134, 13565; (b) Z. Shi, D. C.
Koester, M. Boultadakis-Arapinis and F. Glorius, J. Am. Chem. Soc.,
2013, 135, 12204; (c) X. Yu, S. Yu, J. Xiao, B. Wan and X. Li, J.
Org. Chem., 2013, 78, 5444; (d) S. Yu, S. Liu, Y. Lan, B. Wan and
X. Li, J. Am. Chem. Soc., 2015, DOI: 10.1021/ja511796h; (e) Y.
Zhang, J. Zheng and S. Cui, J. Org. Chem., 2014, 79, 6490; (f) H. W.
Lam, K. Y. Man, W. W. Chan, Z. Zhou and W. Y. Yu, Org. Biomol.
Chem., 2014, 12, 4112; (g) Y. Liang, K. Yu, B. Li, S. Xu, H. Song
and B. Wang, Chem. Commun., 2014, 50, 6130; (h) F. Hu, Y. Xia, F.
Ye, Z. Liu, C. Ma, Y. Zhang and J. Wang, Angew. Chem., Int. Ed.,
2014, 53, 1364; (i) J. Jeong, P. Patel, H. Hwang and S. Chang, Org.
Lett., 2014, 16, 4598; (j) W. Ai, X. Yang, Y. Wu, X. Wang, Y. Li, Y.
Yang and B. Zhou, Chem. −Eur. J., 2014, 20, 17653; (k) B. Ye and
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70
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