Rh(III)-catalyzed synthesis of multisubstituted isoquinoline and pyridine N-oxides from oximes and diazo compounds

Article abstract of DOI:10.1021/ja406338r

Multisubstituted isoquinoline and pyridine N-oxides have been prepared by Rh(III)-catalyzed cyclization of oximes and diazo compounds via aryl and vinylic C-H activation. This intermolecular annulation involving tandem C-H activation, cyclization, and condensation steps proceeds under mild conditions, obviates the need for oxidants, releases N₂ and H₂O as the byproducts, and displays a broad substituent scope.

Full text of DOI:10.1021/ja406338r

Subscriber access provided by University of South Dakota
Communication
Rh(III)-Catalyzed Synthesis of Multisubstituted Isoquinoline
and Pyridine N-Oxides from Oximes and Diazo Compounds
Zhuangzhi Shi, Dennis Christofer Koester, Mélissa Boultadakis-Arapinis, and Frank Glorius
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/ja406338r • Publication Date (Web): 26 Jul 2013
Downloaded from http://pubs.acs.org on July 27, 2013
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a free service to the research community to expedite the
dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts
appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been
fully peer reviewed, but should not be considered the official version of record. They are accessible to all
readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered
to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published
in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just
Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor
changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers
and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors
or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
Journal of the American Chemical Society is published by the American Chemical
Society. 1155 Sixteenth Street N.W., Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 5
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
Rh(III)-Catalyzed Synthesis of Multisubstituted Isoquinoline
and Pyridine N-Oxides from Oximes and Diazo Compounds
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Zhuangzhi Shi, Dennis C. Koester, Mélissa BoultadakisꢀArapinis, and Frank Glorius*
OrganischꢀChemisches Institut, Westfälische WilhelmsꢀUniversität Münster, Corrensstrasse 40, 48149 Münster, Germany
Supporting Information Placeholder
Direct CꢀH activation has advantages over traditional protocols
based on substrate preactivation7 and rhodium complexes such as
ABSTRACT: Multisubstituted isoquinoline and pyridine Nꢀ
oxides have been prepared by Rh(III)ꢀcatalyzed cyclization of
oximes and diazo compounds via aryl and vinylic CꢀH activation.
This intermolecular annulation procedure involving tandem CꢀH
activation, cyclization and condensation steps, proceeds under
mild conditions, obviates the use of oxidants, releases N2 and H2O
as the byproducts, and displays a broad scope with respect to the
substituents.
9
Wilkinson’s
catalyst
(RhCl(PPh3)3),8
Rh2(OAc)4
and
11
[(Cp*RhCl2)2]10,
are particularly promising catalysts in this
transformation. Rh(II)ꢀcatalyzed CꢀH activation with diazo comꢀ
pounds is a powerful method to construct CꢀC bonds.9 Although
carbenoid insertion into alkyl CꢀH bonds is well established,12 the
intermolecular aromatic CꢀH bond coupling has limited precedent
in the literature13 and alkenyl CꢀH activation is unprecedented due
to the preferred cyclopropanation14 and allylic CꢀH activation
process.15 Significant progress was made by Yu in 2012, who first
developed chelationꢀassisted Rh(III)ꢀcatalyzed intermolecular
crossꢀcoupling of diazomalonates with arene CꢀH bonds.16 Very
recently, Rovis et al. also uncovered the cyclization of benꢀ
zamides and donor/acceptor diazo compounds to construct γꢀ
lactams via Rh(III)ꢀcatalyzed CꢀH activation.17 It’s noted that
insertion of carbenoids into vinylic CꢀH bonds is still unsolved
and such a useful coupling is worth further exploration. Herein,
we report the Rh(III)ꢀcatalyzed cyclization of oximes with a class
of diazo compounds containing carbonyl groups, affording the
corresponding polysubstituted isoquinoline and pyridine Nꢀoxides
regioselectively (Figure 1, c).
Isoquinoline and pyridine Nꢀoxides are commonly occurring
structural motifs not only found in numerous pharmaceuticals,
biologically active compounds1 and chiral ligands2 but are also
widely used as powerful intermediates in the functionalization of
isoquinolines and pyridines.3 Traditional methods have been reꢀ
ported for the Nꢀoxidation of isoquinoline and pyridine by differꢀ
ent oxidants such as mCPBA, H2O2, CF3CO3H, MeReO3/H2O2.3
However, their parent heterocycles need to be prepared in adꢀ
vance and suffer from the potential overoxidation of the functionꢀ
alized substituents. Electrophilic cyclizations of oximes are availꢀ
able methods for the preparation of isoquinoline and pyridine Nꢀ
oxides.4 Shin et al. reported that Agꢀ or Auꢀcatalyzed cyclization
of 2ꢀalkynylbenzaldoxime derivatives to the corresponding isoꢀ
quinoline Nꢀoxides (Figure 1, a).5 Nakamura et al. demonstrated
the Cu(I)ꢀcatalyzed synthesis of multisubstituted pyridine Nꢀ
oxides from (E)ꢀOꢀpropargylic α,βꢀunsaturated oximes (Figure 1,
b).6 However, a general method on the intermolecular cyclization
selectively accessing isoquinoline and pyridine Nꢀoxides has not
been developed.
The initial experiments were performed with Oꢀboc oxime ester
and ethyl diazoacetoacetate (2a) in the presence of 2.5 mol%
[(Cp*RhCl2)2] and 15.0 mol% AgOAc as the catalytic system, at
60 oC under an Ar atmosphere in methanol. This set of conditions
indeed afforded the desired product 3aa in 19% yield after 12 h
Table 1. Reaction Development.a
Yiel
T
d
(%)b
19
34
76
99
99
92
69
0
entry
R
catalyst system (mol%)
(oC)
1
2
3
4
5
6
7
8
OBoc
OPiv
OPiv
OAc
[(Cp*RhCl2)2] (2.5) + AgOAc (15.0) 60
[(Cp*RhCl2)2] (2.5) + AgOAc (15.0) 60
[(Cp*RhCl2)2] (2.5) + AgSbF6 (10.0) 60
[(Cp*RhCl2)2] (2.5) + AgSbF6 (10.0) 60
OH (1a) [(Cp*RhCl2)2] (2.5) + AgSbF6 (10.0) 60
OH (1a) [(Cp*RhCl2)2] (1.0) + AgSbF6 (4.0)
OH (1a) [(Cp*RhCl2)2] (2.5) + AgSbF6 (10.0)
60
rt
OH (1a)
AgSbF6 (10.0)
60
a
Conditions: 1 (0.20 mmol), 2a (0.24 mmol), 2.5 mol%
[(Cp*RhCl2)2], 10 mol% AgSbF6, MeOH(1.0 mL), 12 h, under
Ar. b Isolated yield.
Figure 1. Cyclization of oximes to isoquinoline and pyridine Nꢀ
oxides.
ACS Paragon Plus Environment

Journal of the American Chemical Society
Table 2. Rh(III)ꢀcatalyzed isoquinoline Nꢀoxide formation.a Table 3. Rh(III)ꢀcatalyzed pyridine Nꢀoxide formation.a
Page 2 of 5
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
a
Conditions: 1 (0.20 mmol), 2 (0.24 mmol), 2.5 mol%
o
[Cp*RhCl2]2, 10.0 mol% AgSbF6 in MeOH (1.0 mL) at 60 C,
12 h, under Ar; isolated yield.
bearing substituents such as phenyl, ketone, dimethyl phosphoꢀ
nate, phenylsulfone gave the corresponding products in 58ꢀ99%
yield. Among them, the unsymmetrical diketone diazo substrate
2c underwent the desired reaction to only give one regioisomer of
the product 3ac in 99% yield. Interestingly, ethyl 2ꢀdiazoꢀ3ꢀ
oxopropanoate (2g) can also react with 1a, giving the disubstitutꢀ
ed product 3ag in 58% yield.
a
Conditions: 1 (0.20 mmol), 2 (0.24 mmol), 2.5 mol%
o
[Cp*RhCl2]2, 10.0 mol% AgSbF6 in MeOH (1.0 mL) at 60 C,
12 h, under Ar; isolated yield. b Using 5.0 mol% [Cp*RhCl2]2,
20.0 mol% AgSbF6, at 100 oC. c At 100 oC.
without an additional oxidant (Table 1, entry 1). By using the Oꢀ
pivaloyl derivative as substrate, the yield could be improved to
34% (entry 2). The isolated yield of 3aa was dramatically inꢀ
creased to 76% yield using AgSbF6 as halogen scavenger (entry
3). When choosing Oꢀacetyl derivative as substrate, 99% yield of
cyclization product was isolated (entry 4). Interestingly, the simꢀ
plest substrate acetophenone oxime (1a) also gave the product
3aa in 99% yield (entry 5). A slightly reduced yield was obtained
with lower catalyst loading (entry 6) and reactions at room temꢀ
perature became sluggish (entry 7). Control reactions confirmed
that the transformation does not occur in the absence of the
[(Cp*RhCl2)2] (entry 8).
This cyclization was also extended to pyridine Nꢀoxide synthesis
by utilizing α,βꢀunsaturated oximes and diazo compounds as startꢀ
ing materials (Table 2). In the case of the 3ꢀmethylbutꢀ3ꢀenꢀ2ꢀone
oxime (1k) and ethyl diazoacetoacetate (2a), we were delighted to
get 2,3,5,6ꢀtetrasubstituted pyridine Nꢀoxide 4ma in 84% yield
under standard conditions. A variety of α,βꢀunsaturated oximes
1lꢀ1p were tolerated in the reaction, affording the products with
multisubstituents at each position on the pyridine ring. Other
diazo compounds such as 2ꢀdiazoꢀ1ꢀphenylbutaneꢀ1,3ꢀdione (2c),
2ꢀdiazocyclohexaneꢀ1,3ꢀdione (2f) and ethyl 2ꢀdiazoꢀ3ꢀ
oxopropanoate (2g) reacted smoothly with the 3ꢀmethylbutꢀ3ꢀenꢀ
2ꢀone oxime (1k) giving the cyclization products in 58ꢀ72% yield.
With the optimized conditions in hand, we examined the scope
of this CꢀH activation and cyclization process (Table 2). We were
pleased to find other ketoximes 1b and 1c derived from isobuꢀ
tyrophenone and benzophenone afforded the 1,3,4ꢀtrisubstituted
isoquinoline Nꢀoxides 3ba and 3ca in good yield. Aldoxime 1d
was also suitable for this transformation and gave the desired
product 3da in 62% yield. The aldoxime substrates were found to
be tolerant of methyl (1e), methoxy (1f) and fluoro (1g) substituꢀ
tion at the ortho or para position giving the corresponding Nꢀ
oxides 3eaꢀ3ga in 58ꢀ78% yield. However, electronꢀdeficient
groups such as aldoxime 1h with ester group at para position led
to a dramatically decreased conversion. The reaction of metaꢀ
chloroꢀsubstituted oxime 1i produced separable regioisomeric
products 3ia and 3ia’ in 63% total yield with a ratio of 1.8:1
based on NMR analysis of the crude mixture. This reaction was
also applicable to multisubstituted aldoximes such as 1j, which
was converted into compound 3ja in 87% yield. The scope of
other diazo compounds was also investigated with acetophenone
oxime (1a) as partners. The diazo substrates 2bꢀ2g
Rh(III)ꢀcatalyzed cyclization of oxime derivatives with alkynes
represents a useful tool in isoquinoline and pyridine synthesis.18
However, the reactions with unsymmetrical and electronꢀdeficient
alkynes suffer from low regioselectivities and reactivities. Surprisꢀ
ingly, the reaction of acetophenone Oꢀmethyl oxime (1q) and 2a
under our standard conditions afforded isoquinoline 5qa with Nꢀ
O bond cleavage, albeit only in 28% isolated yield. While oxime
ether was not a viable substrate for the intermolecular cyclization,
Figure 2. Rh(III)ꢀcatalyzed isoquinoline formation.
ACS Paragon Plus Environment

Page 3 of 5
Journal of the American Chemical Society
we found that diphenylmethanimine (1r) could be employed in
this isoquinoline formation, giving the corresponding product in
1
88% yield. Additionally, the use of ethyl benzimidate (1s) as a
substrate allowed the formation of 5sa in excellent yield.19 The
findings that this class of diazo compounds can act as equivalents
of electronꢀdeficient alkynes in Rh(III)ꢀcatalyzed isoquinoline
synthesis greatly enriches the diversity of synthetic applications
(Figure 2).
2
3
4
5
6
7
Nꢀoxides are useful synthetic intermediates since they exhibit
different reactivity and regioselectivity compared with the parent
heterocycles (Figure 3). For example, reaction of 3da was carried
out in THF in the presence of TMSCN and DBU to give the cyꢀ
anoisoquinolines 6 in good yield.20 Generation of imidoyl chloꢀ
ride from Nꢀmethylacetamide and its in situ reaction with 3da
gave 1ꢀaminoisoquinoline amide 7 in 83% yield.21 3da was
smoothly alkenylated at the 1ꢀposition with acrylate in 66% yield
by palladiumꢀcatalyzed CꢀH activation using Nꢀoxide as internal
oxidant.22 Based on Fagnou’s method, palladiumꢀcatalyzed regiꢀ
oselective direct arylation of 3da also occurred and gave the
product 9 in moderate yield.23
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Figure 4. Proposed reaction pathway.
of carbonyl intermediate C. When using oxime and imine as subꢀ
strates, the formed enol species can selectively undergo 6π elecꢀ
trocyclization27 and elimination of water to give products 3-5. An
alternative process involving nucleophilic attack by the nitrogen
atom in C on the carbonyl group to form E and E’ directly may
not be ruled out at the present stage.
In summary, we have developed the first example of Rhꢀ
catalyzed isoquinoline and pyridine Nꢀoxide synthesis in which
the aryl and vinylic CꢀH activation serves as the cyclization initiꢀ
ating event. This intermolecular annulation procedure involving
tandem CꢀH activation, cyclization and condensation steps, proꢀ
ceeds under mild conditions, obviates the need for oxidants, reꢀ
leases H2O and N2 as byproducts, and displays a broad scope with
respect to the substituents. This method also provides direct acꢀ
cess to isoquinolines, which cannot be synthesized efficiently by
previous methods. Due to these advantages, this reaction should
be of synthetic value.
Figure 3. Synthetic transformation of isoquinoline Nꢀoxide.
Diazo compound 2h was an efficient substrate for the synthesis
of cyclopropane 10 in the presence of Rh2(OAc)4 as the catalyst.24
However, when 2h was employed in standard conditions with
acetophenone oxime (1a), the Nꢀoxide 3ah was still obtained in
74% isolated yield and the byproducts 10 and 11 were only in
trace amount (eq 1). These result indicated that CꢀH metalation
step is much faster than Rhꢀcarbene formation in our catalytic
system. Meanwhile, the CꢀH bond cleavage process is involved in
the rateꢀdetermining step, since a notable primary kinetic isotope
effect (KIE) of kH/kD = 2.1 was revealed in two parallel experiꢀ
ments (eq 2).25 On the basis of above results, we proposed the
coordination of the substrate 1 to a [RhIIICp*] species as the key
step for the regioselective CꢀH bond cleavage to afford A. This
rhodacycle can coordinate one equivalent of diazo compound 2 to
give intermediate B via Rhꢀcarbene formation pathway.26 Subseꢀ
quently, protonolysis of B delivers the alkylated intermediate C.
Then enol intermediate D is generated in situ by tautomerization
ASSOCIATED CONTENT
Experimental procedures and full spectroscopic data for all new
compounds. This material is available free of charge via the Interꢀ
net at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
glorius@uniꢀmuenster.de
ACKNOWLEDGMENT
Dedicated to Prof. ErnstꢀUlrich Würthwein (WWU Münster) on
the occasion of his 65th birthday. This work was supported by the
Alexander von Humboldt Foundation (Z. S.). Generous financial
support by the European Research Council under the European
Community's Seventh Framework Program (FP7 2007ꢀ
2013)/ERC Grant agreement no 25936 and by the DFG (Leibniz
award) is gratefully acknowledged.
REFERENCES
(1)
(a) The Merck Index on CDꢀROM, v. 12.3, Chapman & Hall,
2000. (b) The Chemistry of Heterocyclic Compounds: Isoquinolines;
Coppola, G. M., Schuster, H. F., Eds.; JohnWiley & Sons: New York,
1981; Vol. 38, Part 3. (c) Donnell, G. O.; Poeschl, R.; Zimhony, O.;
Gunaratnam, M.; Moreira, J. B. C.;Neidle, S.; Evangelopoulos, D.; Bhakꢀ
ta, S.;Malkinson, J. P.; Boshoff,H. I.; Lenaerts, A.;Gibbons, S. J. Nat.
Prod. 2009, 72, 360. (d) Nicholas, G.M.; Blunt, J.W.; Munro,M. H. G. J.
Nat. Prod. 2001, 64, 341. (e) Oberwinkler, S. M.; Nowicki, B.; Pike, V.
W.; Halldin, C.; Sandell, J.; Chou, Y. H.; Gulyas, B.; Brennum, L. T.;
Fardec, L.; Wikstroma, H. V. Bioorg. Med. Chem. 2005, 13, 883.
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 4 of 5
(2)
For review, see: (a) Malkov, A. V.; Kocovsky, P. Eur. J. Org.
Wang, D.; Wang, F.; Song, G.; Li, X. Angew. Chem., Int. Ed. 2012, 51,
Chem. 2007, 29. For recent representative examples, see: (b) Takenaka,
N.; Sarangthem, R. S.; Captain, B. Angew. Chem., Int. Ed. 2008, 47,
9708. (c) Chen, J.; Takenaka, N. Chem. Eur. J. 2009, 15, 7268.
12348. (s) WencelꢀDelord, J.; Nimphius, C.; Wang, H.; Glorius, F. Angew.
Chem., Int. Ed. 2012, 51, 13001. (t) Schröder, N.; WencelꢀDelord, J.;
Glorius, F. J. Am. Chem. Soc. 2012, 134, 8298. (u) Wang, H.; Grohmann,
C.; Nimphius, C.; F. Glorius. J. Am. Chem. Soc. 2012, 134, 19592. (v)
Lian, Y.; Huber, T.; Hesp, K. D.; Bergman, R. G.; Ellman, J. A. Angew.
Chem., Int. Ed. 2013, 52, 629. (w) Neely, J. M.; Rovis, T. J. Am. Chem.
Soc. 2013, 135, 66. (x) Ye, B. Cramer, N. J. Am. Chem. Soc. 2013, 135,
636. (y) Lian, Y.; Bergman, R. G.; Lavis, L. D.; Ellman, J. A. J. Am.
Chem. Soc. 2013, 135, 7122. (z) Liu, G.; Shen, Y.; Zhou, Z.; Lu, X.
Angew. Chem., Int. Ed. 2013, 52, 6033. (aa) Shi, Z.; Grohmann, C.;
Glorius, F. Angew. Chem., Int. Ed. 2013, 52, 5393. (ab) Wang, H.
Schröder, N. Glorius, F. Angew. Chem., Int. Ed. 2013, 52, 5386. (ac) Li,
X.; Yu, S.; Wang, F.; Wan, B.; Yu, X. Angew. Chem., Int. Ed. 2013, 52,
2577. (ad) Shin, K.; Baek, Y.; Chang, S. Angew. Chem., Int. Ed. 2013,
DOI: 10.1002/anie.201302784.
1
2
3
4
5
6
7
8
(3)
(a) Bull, J. A.; Mousseau, J. J.; Pelletier, G.; Charette, A. B.
Chem. Rev. 2012, 112, 2642. (b) Albini, A.; Pietra, S. Heterocyclic Nꢀ
Oxides; CRC Press: Boca Raton, FL, 1991. (c) Youssif, A. ARKIVOC.
2001, 242.
(4)
The iodocyclizations leading to isoquinolineꢀNꢀoxides, see: (a)
Ding. Q.; Wu, J. Adv. Synth. Catal. 2008, 350, 1850. (b) Huo, Z.; Tomeꢀ
ba, H.; Yamamoto, Y. Tetrahedron Lett. 2008, 49, 5531.
(5)
(a) Yeom, H.ꢀS.; Shin, S. Synlett, 2008, 924; (b) Yeom, H.ꢀS.;
9
Lee, Y.; Leeb, J.ꢀE.; Shin, S. Org. Biomol. Chem. 2009, 7, 4744.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(6)
Nakamura, I.; Zhang, D.; Terada, M. J. Am. Chem. Soc. 2010,
132, 7884.
(7)
For recent reviews on CꢀH activation, see (a) Beccalli, S.;
Broggini, G.; Martinelli, M.; Sottocornola, S. Chem. Rev. 2007, 107,
5318. (b) Li, B.ꢀJ.; Yang, S.ꢀD.; Shi, Z.ꢀJ. Synlett 2008, 7, 949. (c)
Ackermann, L.; Vicente, R.; Kapdi, A. R. Angew. Chem., Int. Ed. 2009,
48, 9792. (d) Chen, X.; Engle, K. M.; Wang, D.ꢀH.; Yu, J.ꢀQ. Angew.
Chem., Int. Ed. 2009, 48, 5094. (e) Lautens, M.; Thansandote, P. Chem.
Eur. J. 2009, 15, 5874. (f) Kitamura, T. Eur. J. Org. Chem. 2009, 1111.
(g) Giri, R.; Shi, B.ꢀF.; Engle, K. M.; Maugel, N.; Yu, J.ꢀQ. Chem. Soc.
Rev. 2009, 38, 3242. (h) Daugulis, O.; Do, H.ꢀQ.; Shabashov, D. Acc.
Chem. Res, 2009, 42, 1074. (i) Jazzar, R.; Hitce, J, Renaudat, A.; Sofackꢀ
Kreutzer, J.; Baudoin, O. Chem. Eur. J. 2010, 16, 2654. (j) Lyons, T. W.;
Sanford, M. S. Chem. Rev. 2010, 110, 1147. (k) Shi, Z.; Zhang, C.; Tang,
C.; Jiao, N. Chem. Soc. Rev. 2012, 41, 3381. (l) Satoh, T.; Miura, M.
Chem. Eur. J. 2010, 16, 11212. (m) Cho, S. H.; Kim, J. Y.; Kwak, J.;
Chang, S. Chem. Soc. Rev. 2011, 40, 5068. (n) WencelꢀDelord, J.; Dröge,
T.; Liu, F.; Glorius, F. Chem. Soc. Rev. 2011, 40, 4740. (o) Newhouse, T.;
Baran, P. S. Angew. Chem., Int. Ed. 2011, 50, 3362. (p) Ackermann, L.
Chem. Rev. 2011, 111, 1315. (q) McMurray, L.; O’Hara, F.; Gaunt, M. J.
Chem. Soc. Rev. 2011, 40, 1885. (r) Yeung, C. S.; Dong, V. M. Chem Rev.
2011, 111, 1215. (s) White, M. C. Science 2012, 335, 807. (t) Engle, K.
M.; Mei, T.ꢀS.; Wasa, M.; Yu, J.ꢀQ. Acc. Chem. Res. 2012, 45, 788. (u)
Yamaguchi, J.; Yamaguchi, A. D.; Itami, K. Angew. Chem., Int. Ed. 2012,
51, 8960. (v) Neufeldt, S. R.; Sanford, M. S. Acc. Chem. Res. 2012, 45,
936. (w) Kuhl, N.; Hopkinson, M. N.; WencelꢀDelord, J.; Glorius, F.
Angew. Chem., Int. Ed. 2012, 51, 10236. (x) WencelꢀDelord, J.; Glorius,
F. Nat. Chem. 2013, 5, 369.
(12)
For reviews, see: (a) Doyle, M. P.; Duffy, R.; Ratnikov, M.;
Zhou, L. Chem. Rev. 2010, 110, 704. (b) Davies, H. M. L.; Manning, J. R.
Nature 2008, 451, 417.
(13)
J. Org. Chem. 2009, 74, 6231. (b) Zhao, X.; Wu, G.; Zhang, Y.; Wang, J.
J. Am. Chem. Soc. 2011, 133, 3296. (c) Yao, T.; Hirano, K.; Satoh, T.;
Miura, M. Angew. Chem., Int. Ed. 2012, 51, 775.
(a) Park, C. P.; Nagle, A.; Yoon, C. H.; Chen, C.; Jung, K. W.
(14)
For reviews, see: (a) Moss, R. A. Chem. Rev. 1980, 13, 58. (b)
Lebel, H.; Marcoux, J.; Molinaro, C.; Charette, A. B. Chem. Rev. 2003,
103, 977.
(15)
(16)
Soc. 2012, 134, 13565. A recent work on the intermolecular alkylation of
arenes using αꢀdiazocarbonyl compounds, see: (b) Yu, X.; Yu, S.; Xiao, J.;
Wan,B.; Li, X. J. Org. Chem. 2013, 78, 5444.
(17)
135, 5364.
(18)
Chem. Soc. 2013, 135, 66. (b) Hyster, T. K.; Rovis, T. Chem. Commun.
2011, 47, 11846. (c) Too, P. C.; Noji, T.; Lim, Y.J.; Li, X.; Chiba, S.
Synlett 2011, 2789. For isoquinoline synthesis, see: (d) Jayakumar, J.;
Parthasarathy, K.; Cheng, C.ꢀH. Angew. Chem., Int. Ed. 2012, 51, 197. (e)
Guimond, N.; Gorelsky, S. I.; Fagnou, K. J. Am. Chem. Soc. 2011, 133,
6449. (f) Wei, X.; Zhao, M.; Du, Z.; Li, X. Org. Lett. 2011, 13, 4636. (g)
Zhang, X.; Chen, D.; Zhao, M.; Zhao, J.; Jia, A.; Li, X. Adv. Syn. Cat.
2011, 353, 719. (h) Morimoto, K.; Hirano, K. Satoh, T.; Miura, M. Chem.
Lett. 2011, 40, 600. (i) Too, P. C.; Wang, Y.ꢀF.; Chiba, S. Org. Lett. 2010,
12, 5688. (j) Wang, Y.ꢀF.; Toh, K. K.; Lee, J.ꢀY.; Chiba, S. Angew.
Chem., Int. Ed. 2011, 50, 5927. (k) Fukutani, T.; Umeda, N.; Hirano, K.;
Satoh, T.; Miura, M. Chem. Commun. 2009, 47, 5141.
Lian, Y.; Davies, H. M. L. Acc. Chem. Res. 2012, 45, 923.
(a) Chan, W.ꢀW.; Lo, S.ꢀF.; Zhou, Z.;Yu, W.ꢀY. J. Am. Chem.
Hyster, T. K.; Ruhl, K. E.; Rovis, T. J. Am. Chem. Soc. 2013,
For pyridine synthesis, see: (a) Neely, J. M.; Rovis, T. J. Am.
(8)
For reviews on Rh(I)ꢀcatalyzed CꢀH activations, see: (a) Colby,
D. A.; Bergman, R. G.; Ellman, J. A. Chem. Rev. 2010, 110, 624. (b)
Lewis, J. C.; Bergman, R. G.; Ellman, J. A. Acc. Chem. Res. 2008, 41,
1013. (c) Park, J. R.; Park, J.ꢀW.; Jun, C.ꢀH. Acc. Chem. Res. 2008, 41,
222. (d) Bouffard, J.; Itami, K. Top. Curr. Chem. 2009, 292, 231.
(9)
For reviews on Rh(II)ꢀcatalyzed CꢀH activations with diazo
(19)
Rh/Cuꢀcocatalyzed synthesis of 1Hꢀindazoles from arylimiꢀ
compounds, see: (a) Doyle, M. P.; McKervey, M. A.; Ye, T. Modern
Catalytic Methods for Organic Synthesis with Diazo Compounds; Wileyꢀ
Interscience: New York, 1998; pp 112ꢀ162. (b) Ye, T.; McKervey, M. A.
Chem. Rev. 1994, 94, 1091. (c) Sutton, D. Chem. Rev. 1993, 93, 995. (d)
Zhang, Z.; Wang, J. Tetrahedron 2008, 64, 6577. (e) Davies, H. M. L.;
Beckwith, R. E. J. Chem. Rev. 2003, 103, 2861.
dates and organo azides, see: Yu, D.ꢀG.; Suri, M.; Glorius, F. J. Am.
Chem. Soc. 2013, 135, 8802.
(20)
Heterocycles 1992, 33, 211.
(21)
(22)
Miyashita, A.; Kawashima, T.; Iijima, C.; Higashino, T.
Manley, P. J.; Bilodeau, M. T. Org. Lett. 2002, 4, 3127.
Wu, J.; Cui, X.; Chen, L.; Jiang, G.; Wu, Y. J. Am. Chem. Soc.
(10)
For reviews on Rh(III)ꢀcatalyzed CꢀH activations, see: (a)
2009, 131, 13888.
(23)
Satoh, T.; Miura, M. Chem. Eur. J. 2010, 16, 11212. (b) Song, G.; Wang,
F.; Li, X. Chem. Soc. Rev. 2012, 41, 3651. (c) Patureau, F. W.; Wencelꢀ
Delord, J.; Glorius, F. Aldrichimica Acta 2012, 45, 31.
(a) Campeau, L. C.; Schipper, D. J.; Fagnou, K. J. Am. Chem.
Soc. 2008, 130, 3266. (b) Campeau, L.ꢀC.; Stuart, D. R.; Leclerc, J. P.;
BertrandꢀLaperle, M.; Villemure, E.; Sun, H.ꢀY.; Lasserre, S.; Guimond,
N.; Lecavallier, M.; Fagnou, K. J. Am. Chem. Soc. 2009, 131, 3291. (c)
Schipper, D. J.; ElꢀSalfiti, M.; Whipp, C. J.; Fagnou, K. Tetrahedron
2009, 65, 4977. (d) Schipper, D.J.; Campeau, L.ꢀC.; Fagnou, K. Tetraheꢀ
dron 2009, 65, 3155. Another approach to selective alkenylation and
direct arylation of pyridine Nꢀoxides, see: (e) Cho, S. H.; Hwang, S. J.;
Chang, S. J. Am. Chem. Soc. 2008, 130, 9254.
(11)
Representative Rh(III)ꢀcatalyzed CꢀH activation reactions: (a)
Ueura, K.; Satoh, T.; Miura, M. Org. Lett. 2007, 9, 1407. (b) Morimoto,
K.; Hirano, K.; Satoh, T.; Miura, M. Org. Lett. 2010, 12, 2068. (c) Stuart,
D. R.; BertrandꢀLaperle, M.; Burgess, K. M. N.; Fagnou, K. J. Am. Chem.
Soc. 2008, 130, 16474. (d) Guimond, N.; Fagnou, K. J. Am. Chem. Soc.
2009, 131, 12050. (e) Hyster, T. L. Rovis, T. J. Am. Chem. Soc. 2010,
132, 10565. (f) Rakshit, S.; Patureau, F. W.; Glorius, F. J. Am. Chem. Soc.
2010, 132, 9585. (g) Patureau, F. W.; Besset, T.; Kuhl, N.; Glorius, F. J.
Am. Chem. Soc. 2011, 133, 2154. (h) Hesp, K. D.; Bergman, R. G.;
Ellman, J. A. J. Am. Chem. Soc. 2011, 133, 11430. (i) Muralirajan, K.;
Parthasarathy, K.; Cheng, C.ꢀH. Angew. Chem., Int. Ed. 2011, 50, 4169.
(j) WencelꢀDelord, J.; Nimphius, C.; Patureau, F. W.; Glorius, F. Angew.
Chem. Int. Ed. 2012, 51, 2247. (k) Li, B.ꢀJ.; Wang, H.ꢀY.; Zhu, QꢀL.; Shi,
Z.ꢀJ. Angew. Chem., Int. Ed. 2012, 51, 3948. (l) Shi, Z.; Schröder, N.;
Glorius, F. Angew. Chem., Int. Ed. 2012, 51, 8092. (m) Hyster, T. L.
Knörr, L. Ward, T. R. Rovis, T. Science 2012, 338, 500. (n) Ye, B.
Cramer, N. Science 2012, 338, 504. (o) Kuhl, N. Hopkinson, M. N. Gloꢀ
rius, F. Angew. Chem., Int. Ed. 2012, 51, 8230. (p) Xu, X.; Liu, Y.; Park,
C.ꢀM. Angew. Chem., Int. Ed. 2012, 51, 9372. (q) Karthikeyan, J.;
Haridharan, R.; Cheng, C.ꢀH. Angew. Chem., Int. Ed. 2012, 51, 12343. (r)
(24)
2002, 67, 6535.
(25)
Lim, Y.ꢀH.; McGee, K. F., Jr.; Sieburth, S. M. J. Org. Chem.
(a) Jones, W. Acc. Chem. Res. 2003, 36, 140. (b) Simmons, E.
Hartwig, J. Angew. Chem., Int. Ed. 2012, 51, 3066.
(26)
tion of aryl group may not be ruled out at the present stage, see: ref 16ꢀ17.
(27) Representative work on tandem CꢀH activationꢀ
electrocyclization process, see: (a) Lim, S.ꢀG.; Lee, J. H.; Moon, C. W.;
Hong, J.ꢀB.; Jun, C.ꢀH. Org. Lett. 2003, 5, 2759. (b) Colby, D. A.; Bergꢀ
man, R. G.; Ellman, J. A. J. Am. Chem. Soc. 2006, 128, 5604. (c) Parꢀ
thasarathy, K.; Jeganmohan, M.; Cheng, C.ꢀH. Org. Lett. 2008, 10, 325.
(d) Yotphan, S.; Bergman, R. G.; Ellman, J. A. J. Am. Chem. Soc. 2008,
130, 2452.
An alternative pathway via intramolecular 1,2ꢀmigratory inserꢀ
ACS Paragon Plus Environment

Page 5 of 5
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
5
ACS Paragon Plus Environment