Realized C-H functionalization of aryldiazo compounds via rhodium relay catalysis

Article abstract of DOI:10.1021/acs.orglett.5b00674

An unprecedented C-H functionalization of aryldiazo compounds without a preinstallation of directing group has been realized under mild conditions, which differs from former reports in its use of diazo compounds as coupling partners in directed C-H activations. This novel transformation has been realized by a rhodium self-relay catalysis, a tandem process of the in situ formation of a directing group and sequential C-H bond activation.

Full text of DOI:10.1021/acs.orglett.5b00674

Letter
pubs.acs.org/OrgLett
Realized C−H Functionalization of Aryldiazo Compounds via
Rhodium Relay Catalysis
Lin Qiu,† Daorui Huang,‡ Guangyang Xu,† Zhenya Dai,‡ and Jiangtao Sun*,†,§
†School of Pharmaceutical Engineering & Life Science, Changzhou University, Changzhou 213164, P. R. China
‡School of Pharmacy, China Pharmaceutical University, Nanjing, Nanjing 210009, P. R. China
§Jiangsu Key Laboratory of Advanced Catalytic Materials and Technology, Changzhou University, Changzhou 213164, P. R. China
S
* Supporting Information
ABSTRACT: An unprecedented C−H functionalization of
aryldiazo compounds without a preinstallation of directing
group has been realized under mild conditions, which differs
from former reports in its use of diazo compounds as coupling
partners in directed C−H activations. This novel trans-
formation has been realized by a rhodium self-relay catalysis,
a tandem process of the in situ formation of a directing group
and sequential C−H bond activation.
Scheme 1. Diazo-Involved C−H Functionalizations
ransition-metal catalyzed directed C−H bond functional-
Tization has emerged as a powerful tool for the rapid
construction of carbon−carbon, carbon−heteroatom bonds.1
Generally, a directing-group-containing substrate and function-
alized molecules such as alkene, alkyne, which act as coupling
partners, are prerequisites.2 Meanwhile, as highly reactive
precursors, the nature of diazo compounds makes them good
coupling partners in C−H activations. In 2011, Wang reported
a seminal copper-catalyzed direct benzylation/allylation of 1,3-
azoles with N-tosylhydrones.3 Later, Yu described the
intermolecular cross-coupling of diazomalonates with arene
C−H bonds.4 Rovis5 and Glorius6 demonstrated the use of
donor/acceptor, acceptor/acceptor diazo compounds in
constructing heterocycles, respectively. Pioneered by these
elegant works, the diazo-involved C−H activation attracted
much attention, and many useful approaches have been
developed.7 Recently, Li and co-workers designed phenacyl-
triethylammonium salts as novel arene substrates for redox-
neutral couplings with α-diazo esters via a C−H activation
pathway.8
Despite this, the published reactions have been limited to the
use of diazo compounds as coupling partners by dediazoniza-
tion and generation of metal carbon species (Scheme 1, A). An
intriguing issue is whether the diazo compounds can be
employed as the activated targets, not as coupling partners,
which, to our knowledge, has not been reported previously.
However, the challenges remain: First, how does the directing
group appear? Second, the extremely easy decomposition of the
diazo moiety in the presence of a late transition metal,
especially a rhodium complex, increases the difficulty.9 Third,
unexpected side reactions are common phenomena in diazo-
involved transformations. To circumvent these challenges and
continuing with our interest in diazo chemistry,10 herein we
describe the first example of rhodium-catalyzed C−H
functionalization of aryldiazo compounds under mild con-
ditions (Scheme 1, B). This novel approach provides a distinct
strategy for the formal C−H activation of diazo substrates
through in situ formation of a directing group from an active
precursor followed by sequential C−H and N−N bond
activations.
To address these challenges, a rational strategy needed to be
developed. Our former observations on diazo cross-coupling
reactions revealed that, through controlling of the reaction
parameters, the intermolecular coupling of two diazo
compounds could afford N-containing intermediates instead
of alkenes via selective decomposition one of two diazo
moieties (Scheme 2).10f Therefore, we reasoned that the C−H
functionalization of the diazo substrate might be realized
through a tandem process. Nevertheless, to avoid of unexpected
Received: March 6, 2015
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.5b00674
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
was obtained when benzoic acid (0.25 eq to 1a) was added
(entry 2), which was further improved to 82% when a mixed
solvent (CH2Cl2/MeOH, 1:4) was used. Other solvents such as
CH2Cl2, 1,2-dichloroethane, toluene, and acetonitrile did not
afford any 3a (entries 3 to 6). Next, several acids were also
examined but gave 3a in low to moderate yields (entries 8−10).
Further screening of rhodium catalysts found that [Cp*RhCl2]2
remained as the best choice. The use of Rh2(OAc)4, Rh2(esp)2,
and [RhCl(cod)]2 did not give 3a at all (entries 12−14), while
Cp*Rh(H2O)3(OTf)2 afforded moderate yield (entry 15). The
reaction was sluggish when performed at room temperature
(entry 16). Moreover, lower catalyst loading still gave 3a in the
same yield (entry 17). However, the yield was very low when
performed under nitrogen (entry 18). Interestingly, when an
external co-oxidant such as AgNO3/Cu(OAc)2 was used, 3a
was obtained in 68% yield (entry 11).
Scheme 2. Our Plan toward C−H Functionalization of Diazo
Compounds
side reactions, one key concern is that the potential catalytic
system should produce the directing-group-containing inter-
mediate in situ rapidly and proceed smoothly to the following
C−H activation.
We began our study by utilizing diazo (1a) and alkyne (2a)
as model substrates in the reaction at 80 °C under air (Table
1). Initially, no 3a was detected when [Cp*RhCl2]2 (5 mol %)
was used in methanol (entry 1). Gratifyingly, 71% yield of 3a
With the optimal reaction conditions in hand, we further
investigated the reaction of 1a with a variety of alkynes
(Scheme 3). All of the reactions proceeded well to afford 3 in
a,b
Scheme 3. Substrate Scope of Alkynes
a
Table 1. Optimization of the Reaction Conditions
b
yield
entry
catalyst
additive
solvent
MeOH
(%)
1
2
3
4
5
6
7
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
0
71
0
PhCO2H
PhCO2H
PhCO2H
PhCO2H
PhCO2H
PhCO2H
MeOH
CH2Cl2
(CH2)2Cl2
toluene
0
0
CH3CN
0
CH2Cl2/MeOH
(1:4)
82
8
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
Rh2(OAc)4
AcOH
TsOH
PivOH
CH2Cl2/MeOH
(1:4)
55
30
60
68
0
9
CH2Cl2/MeOH
(1:4)
10
CH2Cl2/MeOH
(1:4)
c
11
[Ag]/[Cu] CH2Cl2/MeOH
(1:4)
a
Reaction conditions: 1 (0.2 mmol), 2 (0.22 mmol), PhCO2H (0.05
mmol), [Cp*RhCl2]2 (0.005 mmol), CH2Cl2 (1 mL), MeOH (4 mL),
12
13
14
15
PhCO2H
PhCO2H
PhCO2H
CH2Cl2/MeOH
(1:4)
b
80 °C, 12 h. Isolated yields.
Rh2(esp)2
CH2Cl2/MeOH
(1:4)
0
[RhCl(cod)]2
CH2Cl2/MeOH
(1:4)
0
moderate to high yields. For the diarylalkynes, the phenyl ring
bearing an electron-donating group such as a methyl and
methoxy group afforded the corresponding products in higher
yields (3b and 3c to 3d). A similar phenomenon was also
observed for dialiphatic-substituted alkyne (3j). However,
unsymmetric diarylalkynes gave two regioisomers in nearly a
1:1 ratio (3e/3e′ and 3f/3f′).11 When the arylalkylalkynes were
employed, the desired products were obtained in moderate to
high yields with excellent regioselectivities (3g and 3h).
Notably, the alkynes bearing a hydroxy group or a N,N-
tosylmethyl-substituted amine were also tolerated and afforded
3i and 3k in 70% and 82% yield, respectively.11
Cp*Rh(H2O)3(OTf)2 PhCO2H
CH2Cl2/MeOH
(1:4)
67
26
82
<5
d
16
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
PhCO2H
PhCO2H
PhCO2H
CH2Cl2/MeOH
(1:4)
e
17
CH2Cl2/MeOH
(1:4)
f
18
CH2Cl2/MeOH
(1:4)
a
Reactions conditions: To a Schlenk tube (10 mL) were added [Rh]
(5 mol %), additive (0.05 mmol), and solvent (5 mL). Then 1a (0.2
mmol) and 2a (0.22 mmol) were added under air. The tube was sealed
b
c
Next, to demonstrate the generality of the reaction, the scope
of substrates was further examined. As presented in Scheme 4,
the reactions between alkynes and aryl/aryl, aryl/alkyl diazo
and stirred at 80 °C for 12 h. Isolated yield of 3a. AgNO3 (0.04
mmol) and Cu(OAc)2 (0.2 mmol) were added. Performed at rt. 2.5
mol % of [Rh]. Under nitrogen.
d
e
f
B
DOI: 10.1021/acs.orglett.5b00674
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a,b
Scheme 4. Substrate Scope
Scheme 6. Proposed Catalytic Cycle
a
Reaction conditions: 1 (0.2 mmol), 2 (0.22 mmol), PhCO2H (0.05
mmol), [Cp*RhCl2]2 (0.005 mmol), CH2Cl2 (1 mL), MeOH (4 mL),
b
80 °C, 12 h. Isolated yields.
compounds proceeded smoothly to furnish the corresponding
products in moderate to good yields. Generally, two
regioisomers were obtained for unsymmetric diaryl diazo
compounds (4d/4d′, 2:1 and 4e/4e′, 1:1),11 while 4f was
isolated as single isomer. The aryl/alkyl diazo compounds were
well-tolerated in this reaction, and the desired products were
obtained in moderate to high yields (4k−o).
The unprecedented directed C−H bond functionalization of
aryldiazo compounds prompted us to perform further
exploration in order to understanding the reaction process.
Thus, control experiments were conducted. First, without the
addition of benzoic acid, we found that 5a was obtained in
almost quantitative yield in 30 min at room temperature
catalyzed by 1 mol % of [Cp*RhCl2]2 (Scheme 5, a) without
Rh-catalyzed azine formation via diazo coupling. First, the
reaction between 1a and rhodium catalyst generates metal−
carbene intermediate A, which rapidly undergoes attack by
another molecular of 1a to afford intermediate B. Then
intramolecular rearrangement of B associated with the loss of
rhodium catalyst produces azine 5a. Next, the reaction of 5a
and rhodium catalyst affords intermediate C via C−H bond
activation, which followed by insertion of alkyne into the Rh−C
bond gives rise to intermediate D. Finally, the reductive
elimination and N−N bond cleavage of D in the presence of air
and benzoic acid affords two molecules of 3a and regenerates
the active rhodium catalyst. Alternatively, coordination of 5a
with alkyne generates intermediate E.12 Insertion of alkyne into
the Rh−C bond affords intermediate F, which undergoes
reductive elimination and N−N bond cleavage to release 3a
and an active intermediate G. Next, G coordinates to another
molecule of alkyne followed by insertion to give rise to
intermediate I. Subsequent oxidation by air in the presence of
benzoic acid furnishes 3a and regenerates the catalyst.
Scheme 5. Control Experiments
In summary, we have demonstrated an unprecedented
rhodium-catalyzed C−H functionalization of aryl diazo
compounds. This novel transformation features a tandem
process of diazo coupling, C−H bond activation, and N−N
bond cleavage in the presence of a single rhodium catalyst.
Further, an external co-oxidant such as copper complex, which
is commonly used in C−H bond activation, is not needed.
the detection of alkene. Next, 5a was treated under standard
reaction conditions (same with Scheme 3), and 3a was isolated
in 90% yield (Scheme 5, b).12 These results disclosed that the
rhodium-catalyzed C−H functionalization of donor/donor
diazo compounds is a tandem process.
On the basis of the above experiments, a plausible reaction
mechanism is proposed (Scheme 6). The first catalytic cycle is
ASSOCIATED CONTENT
* Supporting Information
■
S
Experimental procedures along with characterizing data and
copies of NMR spectra. This material is available free of charge
via the Internet at http://pubs.acs.org.
C
DOI: 10.1021/acs.orglett.5b00674
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Rev. 2009, 38, 3061. (c) Doyle, M. P.; Duffy, R.; Ratnikov, M.; Zhou,
L. Chem. Rev. 2010, 110, 704. (d) Davies, H. M. L.; Denton, J. R.
Chem. Soc. Rev. 2011, 40, 1857. (e) Gillingham, D.; Fei, N. Chem. Soc.
Rev. 2013, 42, 4918.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: jtsun08@gmail.com; jtsun@cczu.edu.cn.
(10) (a) Liu, G.; Li, J.; Qiu, L.; Liu, L.; Xu, G.; Ma, B.; Sun, J. Org.
Biomol. Chem. 2013, 11, 5998. (b) Ding, D.; Liu, G.; Xu, G.; Li, J.;
Wang, G.; Sun, J. Org. Biomol. Chem. 2014, 12, 2533. (c) Ding, D.; Lv,
X.; Li, J.; Xu, G.; Ma, B.; Sun, J. Chem.Asian J. 2014, 9, 1539.
(d) Guo, H.; Zhang, D.; Zhu, C.; Li, J.; Xu, G.; Sun, J. Org. Lett. 2014,
16, 3110. (e) Zhang, D.; Xu, G.; Ding, D.; Zhu, C.; Li, J.; Sun, J.
Angew. Chem., Int. Ed. 2014, 53, 11070. (f) Xu, G.; Zhu, C.; Gu, W.; Li,
J.; Sun, J. Angew. Chem., Int. Ed. 2015, 54, 883.
(11) CCDC 1046937 (3e′), 1046938 (3k), 1046939 (4d), and
1046940 (4e′) containing the supplementary crystallographic data for
this paper can be obtained free of charge from the Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/
cif.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the National Natural Science Foundation of China
(No. 21172023, 21102180), the Priority Academic Program
Development of Jiangsu Higher Education Institutions, and
Jiangsu Key Laboratory of Advanced Catalytic Materials and
Technology (BM2012110) for their financial support.
REFERENCES
■
(12) Han, W.; Zhang, G.; Li, G.; Huang, H. Org. Lett. 2014, 16, 3532.
(1) For selected reviews on directed C−H activations, see: (a) Colby,
D. A.; Bergman, R. G.; Ellman, J. A. Chem. Rev. 2010, 110, 1147.
(b) Wencel-Delord, J.; Droge, T.; Liu, F.; Glorius, F. Chem. Soc. Rev.
̈
2011, 40, 4740. (c) Satoh, T.; Miua, M. Chem.Eur. J. 2010, 16,
11212. (d) Song, G. Y.; Wang, F.; Li, X. Chem. Soc. Rev. 2012, 41,
3651. (e) Kuhl, N.; Schroder, N.; Glorius, F. Adv. Synth. Catal. 2014,
̈
356, 1443.
(2) For selected recent examples on the use of alkynes and alkenes as
coupling partners, see: (a) Dai, H.-X.; Li, G.; Zhang, X.-G.; Stepan, A.
F.; Yu, J.-Q. J. Am. Chem. Soc. 2013, 135, 7567. (b) Neely, J. M.; Rovis,
T. J. Am. Chem. Soc. 2013, 135, 66. (c) He, R.; Huang, Z.; Zheng, Q.;
Wang, C. Angew. Chem., Int. Ed. 2014, 53, 4950. (d) Yu, D. G.; de
Azambuja, F.; Gensch, T.; Daniliuc, C. G.; Glorius, F. Angew. Chem.,
Int. Ed. 2014, 53, 9650. (e) Grigorjeva, L.; Daugulis, O. Angew. Chem.,
Int. Ed. 2014, 53, 10209. (f) Zhang, X.; Qi, Z.; Li, X. Angew. Chem., Int.
Ed. 2014, 53, 10794. (g) Zhang, H.; Wang, K.; Wang, B.; Yi, H.; Hu,
F.; Li, C.; Zhang, Y.; Wang, J. Angew. Chem., Int. Ed. 2014, 53, 13234.
(h) Xu, W.; Yoshikai, Y. Angew. Chem., Int. Ed. 2014, 53, 14166.
(i) Fukui, Y.; Liu, P.; Liu, Q.; He, Z.; Wu, N.; Tian, P.; Lin, G. J. Am.
Chem. Soc. 2014, 136, 15607. (j) Shang, M.; Wang, H.-L.; Sun, S.-Z.;
Dai, H.-X.; Yu, J.-Q. J. Am. Chem. Soc. 2014, 136, 3354.
(3) (a) Zhao, X.; Wu, G.; Zhang, Y.; Wang, J. J. Am. Chem. Soc. 2011,
133, 3296. (b) Xiao, Q.; Zhang, Y.; Wang, J. Acc. Chem. Res. 2013, 46,
236.
(4) Chan, W.-W.; Lo, S.-F.; Zhou, Z.; Yu, W.-Y. J. Am. Chem. Soc.
2012, 13, 13565.
(5) Hyster, T. K.; Ruhl, K. E.; Rovis, T. J. Am. Chem. Soc. 2013, 125,
5364.
(6) Shi, Z.; Koester, D. C.; Boultadakis-Arapinis, M.; Glorius, F. J.
Am. Chem. Soc. 2013, 135, 12204.
(7) (a) Yu, X.; Yu, S.; Xiao, J.; Wan, B.; Li, X. J. Org. Chem. 2013, 78,
5444. (b) Hu, F.; Xia, Y.; Ye, F.; Liu, Z.; Ma, C.; Zhang, Y.; Wang, J.
Angew. Chem., Int. Ed. 2014, 53, 1364. (c) Ai, W.; Yan, X.; Wu, Y.;
Wang, X.; Li, Y.; Yang, Y.; Zhou, B. Chem.Eur. J. 2014, 20, 17653.
(d) Jeong, J.; Patel, P.; Hwang, H.; Chang, S. Org. Lett. 2014, 16, 4598.
(e) Lam, H.-W.; Man, K.-Y.; Chan, W.-W.; Zhou, Z.; Yu, W.-Y. Org.
Biomol. Chem. 2014, 12, 4112. (f) Liang, Y.; Yu, K.; Li, B.; Xu, S.;
Song, H.; Wang, B. Chem. Commun. 2014, 50, 6130. (g) Ye, B.;
Cramer, N. Angew. Chem., Int. Ed. 2014, 53, 7896. (h) Xia, Y.; Liu, Z.;
Liu, Z.; Ge, R.; Ye, F.; Hossain, M.; Zhang, Y.; Wang, J. J. Am. Chem.
Soc. 2014, 136, 3613. (i) Shi, J.; Zhou, J.; Yan, Y.; Jia, J.; Liu, X.; Song,
H.; Xu, H.; Yi, W. Chem. Commun. 2015, 51, 668. (j) Li, X.; Sun, M.;
Liu, K.; Jin, Q.; Liu, P. Chem. Commun. 2015, 51, 2380. (k) Xia, Y.;
Liu, Z.; Feng, S.; Zhang, Y.; Wang, J. J. Org. Chem. 2015, 80, 223.
(l) Hu, F.; Xia, Y.; Ma, C.; Zhang, Y.; Wang, J. Chem. Commun. 2015,
DOI: 10.1039/C5CC00497G. (m) Zhao, D.; Kim, J. H.; Stegemann,
L.; Strassert, C. A.; Glorius, F. Angew. Chem., Int. Ed. 2015,
DOI: 10.1002/anie.201411994.
(8) Zhao, H.; Fan, X.; Wan, B.; Li, X. J. Am. Chem. Soc. 2015, 137,
1623.
(9) For reviews, see: (a) Davies, H. M. L.; Beckwith, R. E. J. Chem.
Rev. 2003, 103, 2861. (b) Davies, H. M. L.; Denton, J. R. Chem. Soc.
D
DOI: 10.1021/acs.orglett.5b00674
Org. Lett. XXXX, XXX, XXX−XXX