Rhodium-catalyzed oxidative coupling of aromatic imines with internal alkynes via regioselective C-H bond cleavage

Article abstract of DOI:10.1039/b910198e

The rhodium-catalyzed oxidative coupling of aromatic imines with alkynes effectively proceeds via regioselective C-H bond cleavage to produce indenone imine and isoquinoline derivatives. The Royal Society of Chemistry 2009.

Full text of DOI:10.1039/b910198e

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Rhodium-catalyzed oxidative coupling of aromatic imines with internal
alkynes via regioselective C–H bond cleavagew
Tatsuya Fukutani, Nobuyoshi Umeda, Koji Hirano, Tetsuya Satoh* and Masahiro Miura*
Received (in Cambridge, UK) 22nd May 2009, Accepted 7th July 2009
First published as an Advance Article on the web 28th July 2009
DOI: 10.1039/b910198e
The rhodium-catalyzed oxidative coupling of aromatic imines
with alkynes effectively proceeds via regioselective C–H bond
cleavage to produce indenone imine and isoquinoline derivatives.
performed to form indenone imine and isoquinoline
derivatives, respectively.10,11 These compounds are useful as
synthetic intermediates for various fine chemicals including
medicines and organic materials.12
In an initial attempt, benzylideneaniline (1a) (0.5 mmol) was
treated with diphenylacetylene (2a) (0.5 mmol) under conditions
similar to those employed for the coupling of benzoic acids
with 2a.6c,d Thus, in the presence of [Cp*RhCl2]2 (0.005 mmol)
and Cu(OAc)2ꢀH2O (1 mmol) in o-xylene (3 mL) at 80 1C
under N2, N-(2,3-diphenyl-1H-inden-1-ylidene)benzenamine
(3a) was formed in only 4% yield after 10 h (entry 1 in
Table 1; Cp* = pentamethylcyclopentadienyl). In DMF, the
product yield dramatically increased to 61% (entry 2), and the
use of an excess amount of 1a (1 mmol) improved the product
yield slightly (entry 3). A comparable result was obtained at
100 1C, while the yield of 3a was slightly decreased at 60 1C
(entries 4 and 5). Finally, the yield was enhanced up to 85% by
increasing the amount of [Cp*RhCl2]2 to 1 mol% (entry 6).
The present reaction was, however, sluggish under air with a
catalytic amount of the copper species (entry 7).
Transition metal-catalyzed organic reactions via C–H bond
cleavage have attracted much attention from an atom-
economic point of view, and various catalytic processes involving
different modes to activate the ubiquitously available bond
have been developed.1 Among the most promising activation
strategies is utilization of the proximate effect by coordination
of a functional group in a given substrate to the metal center of
a catalyst, which brings about regioselective ortho C–H bond
activation and functionalization. Particularly, reactions using
alkynes as a coupling partner are useful as methods for the
synthesis of ortho-vinylated aromatic compounds, which are
important precursors of various condensed aromatic and
heteroaromatic derivatives (Scheme 1, path a). As precedent
examples, the ortho-vinylation reactions of ketones,2
naphthols,3 imines4 and azobenzenes5 have been developed.
Meanwhile, oxidative coupling via C–H bond cleavage
appears to be an advanced method to produce such benzannulated
compounds in one step, simply and directly (Scheme 1, path b).
We have succeeded in conducting the oxidative coupling of
benzoic acids6 and salicylaldehydes7 with alkynes efficiently
under rhodium catalysis to afford isocoumarin and chromone
derivatives, respectively. More recently, Fagnou et al. reported
the synthesis of indoles from anilides by using a related
catalyst system.8 During our further study of rhodium-
catalyzed oxidative coupling,9 it has been revealed that the
oxidative coupling of aromatic imines such as benzylidene-
anilines and benzophenone imine with alkynes can also be
Table 2 summarizes the results for the reactions of various
benzylideneanilines 1a–g with internal alkynes 2a–e. Chloro-,
methyl- and methoxy-substituted benzylideneanilines 1b–f reacted
with 2a smoothly to produce the corresponding indenone imines
3b–f in 71–99% yields (entries 1–5). N-(2-Naphthylmethylene)-
aniline (1g) underwent the coupling with 2a to selectively give 3g in
97% yield (entry 6). However, an N-alkylimine, benzylidene-tert-
butylamine, was recovered almost quantitatively under similar
conditions. The reactions of 1a with diarylacetylenes 2b–d or
Table 1 The reaction of N-benzylideneaniline (1a) with diphenyl-
acetylene (2a)a
Yield of
Entry 1a/mmol [Cp*RhCl2]2/mmol Temp/1C Time/h 3a (%)b
1c
2
3
4
0.5
0.5
1
1
1
0.005
0.005
0.005
0.005
0.005
0.01
80
80
80
60
100
80
80
10
10
10
10
2
4
61
67
56
Scheme 1 Synthesis of condensed (hetero)aromatic compounds via
regioselective C–H bond cleavage.
5
65
85 (76)
28
Department of Applied Chemistry, Faculty of Engineering,
Osaka University, Suita, Osaka 565-0871, Japan.
E-mail: satoh@chem.eng.osaka-u.ac.jp, miura@chem.eng.osaka-u.ac.jp
Fax: +81 66879 7362; Tel: +81 66879 7361
w Electronic supplementary information (ESI) available: Experimental
procedures, spectral data and selected crystal data for 3a.
CCDC 733862. For crystallographic data in CIF or other electronic
format, see DOI: 10.1039/b910198e
6
1
1
6
6
7d
0.01
a
Reaction conditions: 2a (0.5 mmol), Cu(OAc)2ꢀH2O (1 mmol), DMF
b
(3 mL) under N2. GC yield based on the amount of 2a used. Value in
c
d
parentheses indicates yield after purification. In o-xylene. Using
Cu(OAc)2ꢀH2O (0.1 mmol) under air.
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Table 2 The reaction of N-(arylmethylene)anilines 1 with alkynes 2a
Entry
1
2
Time/h
Product, yield (%)b
1
2
3
4
5
1b: R1 = Cl; R2 = H
1c: R1 = Me; R2 = H
1d: R1 = H; R2 = Cl
1e: R1 = H; R2 = OMe
1f: R1 = Cl; R2 = Cl
2a
10
6
6
8
10
3b: R1 = Cl; R2 = H, 82 (78)
3c: R1 = Me; R2 = H, 83 (83)
3d: R1 = H; R2 = Cl, 99 (99)
3e: R1 = H; R2 = OMe, 71 (54)
3f: R1 = Cl; R2 = Cl, 86 (86)
6
1g
2a
4
3g, 97 (91)
7
8
9
1a
2b: X = Cl
2c: X = Me
2d: X = OMe
4
4
4
3h: X = Cl, 65 (65)
3i: X = Me, 68 (65)
3j: X = OMe, 46 (45)
10
1a
2e
12
3k, 40 (32)
a
b
Reaction conditions: 1 (1 mmol), 2 (0.5 mmol), [(Cp*RhCl2)2] (0.01 mmol), Cu(OAc)2ꢀH2O (1 mmol), DMF (3 mL) at 80 1C under N2. GC yield
based on the amount of 2 used. Value in parentheses indicates yield after isolation.
4-octyne (2e) also proceeded to afford 3h–3k, respectively
(entries 7–10). In contrast to such internal alkynes, 1-phenyl-
acetylene did not couple with 1a at all, and an alkyne dimer,
diphenylbutadiyne, was formed quantitatively.
A plausible mechanism for the reaction of benzylideneaniline
(1a) with alkynes 2 is illustrated in Scheme 2, in which neutral
ligands are omitted for clarity. In the first step, coordination of
the nitrogen atom of 1a to an RhIIIX3 species appears to be a key
step for the regioselective C–H bond cleavage to afford A. Then,
alkyne insertion to form B, intramolecular insertion of the imino
Scheme 2 A plausible mechanism for the reaction of 1a with 2.
moiety to form C, and b-hydrogen elimination may successively
occur to give product 3.13 The RhIX species, formed by release of
HX, may be oxidized by a copper(II) salt to regenerate RhIIIX3.
Under similar conditions, benzophenone imine (4) was found to
very efficiently undergo the oxidative coupling with alkynes 2
(Table 3). Thus, treatment of 4 (0.5 mmol) with 2a (0.5 mmol) in
the presence of [Cp*RhCl2]2 (0.005 mmol) and Cu(OAc)2ꢀH2O
(1 mmol) in DMF (3 mL) at 80 1C under N2 for 2 h gave 1,3,4-
triphenylisoquinoline (5a) in 98% yield (entry 1). Similarly,
3,4-diaryl- and 3,4-dipropyl-2-phenylisoquinolines 5b–e were
obtained in good yields by the reactions of 4 with 2b–e
(entries 2–5). 1-Phenylpropyne (2f) also reacted with 4 to give
4-methyl-1,3-diphenylisoquinoline (5f), along with a small amount
of an unidentified isomer (5f : isomer = 89 : 11) (entry 6).
Compound 5f was separable from the isomer and isolated in
85% yield. In contrast to free-nitrogen imine 4, benzophenone
phenylimine (6) did not undergo oxidative coupling with 2a under
similar conditions. In this case, only ortho-vinylation (Scheme 1,
path a) took place to form a non-oxidative coupling product 7
(Scheme 3).
As depicted briefly in Scheme 4, isoquinoline 5 may be
formed via five-membered (D) and seven-membered (E)
rhodacycle intermediates. Meanwhile, the reaction of
N-substituted imine 6 seems to proceed via intermediates A0
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Table 3 The reaction of benzophenone imine (4) with alkynes 2a
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M. Miura, J. Synth. Org. Chem., Jpn., 2006, 64, 1199; (p) B. L. Conley,
W. J. Tenn III, K. J. H. Young, S. K. Ganesh, S. K. Meier,
V. R. Ziatdinov, O. Mironov, J. Oxgaard, J. Gonzales,
W. A. Goddard III and R. A. Periana, J. Mol. Catal. A: Chem.,
2006, 251, 8; (q) M. Miura and T. Satoh, in Handbook
of C–H Transformations, ed. G. Dyker, Wiley-VCH, Weinheim, 2005,
vol. 1, p. 223; (r) M. Miura and T. Satoh, Top. Organomet. Chem.,
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2004, 2, 2551; (t) F. Kakiuchi and N. Chatani, Adv. Synth. Catal., 2003,
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211; (w) F. Kakiuchi and S. Murai, Acc. Chem. Res., 2002, 35, 826;
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47; (z) G. Dyker, Angew. Chem., Int. Ed., 1999, 38, 1698.
Product,
yield (%)b
Entry
2
R1
R2
1
2
3
4
5
6
2a
2b
2c
2d
2e
2f
Ph
Ph
5a, 98 (90)
5b, 86 (86)
5c, 99 (92)
5d, 95 (95)
5e, 85 (85)
5f, 99c (85)
4-ClC6H4
4-MeC6H4
4-MeOC6H4
Pr
4-ClC6H4
4-MeC6H4
4-MeOC6H4
Pr
Me
Ph
a
Reaction conditions: 2 (0.5 mmol), 4 (0.5 mmol), [Cp*RhCl2]2
(0.005 mmol), Cu(OAc)2ꢀH2O (1 mmol), DMF (3 mL) at 80 1C for
b
2 h under N2. GC yield based on the amount of 2 used. Value in
c
parentheses indicates yield after purification. Contaminated with an
isomer (5f : isomer = 89 : 11).
2 (a) F. Kakiuchi, T. Uetsuhara, Y. Tanaka, N. Chatani and S. Murai,
J. Mol. Catal. A: Chem., 2002, 182, 511; (b) F. Kakiuchi,
Y. Yamamoto, N. Chatani and S. Murai, Chem. Lett., 1995, 681.
3 (a) T. Satoh, Y. Nishinaka, M. Miura, H. Morisaka, M. Nomura,
H. Matsui and C. Yamaguchi, Bull. Chem.Soc. Jpn., 2001, 74,
1727; (b) T. Satoh, Y. Nishinaka, M. Miura and M. Nomura,
Chem. Lett., 1999, 615.
Scheme 3 The reaction of benzophenone phenylimine (6) with 2a.
4 (a) T. Katagiri, T. Mukai, T. Satoh, K. Hirano and M. Miura, Chem.
Lett., 2009, 38, 118; (b) D. A. Colby, R. G. Bergman and J. A. Ellman,
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and C.-H. Cheng, Org. Lett., 2008, 10, 325; (d) S.-G. Lim, J. H. Lee,
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5 U. Durr and H. Kisch, Synlett, 1997, 1335.
¨
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Chem., 2008, 80, 1127; (c) K. Ueura, T. Satoh and M. Miura,
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7 M. Shimizu, H. Tsurugi, T. Satoh and M. Miura, Chem.–Asian J.,
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8 D. R. Stuart, M. Bertrand-Laperle, K. M. N. Burgess and
K. Fagnou, J. Am. Chem. Soc., 2008, 130, 16474.
Scheme 4 A plausible mechanism for the reactions of 4 and 6 with 2.
9 (a) N. Umeda, H. Tsurugi, T. Satoh and M. Miura, Angew. Chem., Int.
Ed., 2008, 47, 4019; (b) T. Uto, M. Shimizu, K. Ueura, T. Tsurugi,
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2438. Related non-oxidative alkyne coupling: (d) T. Katagiri,
H. Tsurugi, T. Satoh and M. Miura, Chem. Commun., 2008, 3405.
10 Synthesis of similar isoquinolines from ortho-halogenated benzylidene
imines: (a) K. R. Roesch and R. C. Larock, J. Org. Chem., 1998, 63,
5306; (b) K. R. Roesch, H. Zhang and R. C. Larock, J. Org. Chem.,
2001, 66, 8042.
and B0, related to A and B in Scheme 2, rather than D and E.
Then, protonolysis of the C–Rh bond in B0 may occur,
in preference to intramolecular insertion of the sterically
hindered imino moiety, to afford 7.
In summary, we have demonstrated that the rhodium-catalyzed
oxidative coupling of aromatic imines with alkynes proceeds
efficiently accompanied by regioselective C–H bond cleavage.
These reactions provide straightforward routes to benzannulated
compounds such as indenone imine or isoquinoline derivatives,
which are useful intermediates for medicines and organic materials.
We thank Dr N. Kanehisa, Osaka University, for X-ray
crystal structure analysis. This work was partly supported by
Grants-in-Aid from the Ministry of Education, Culture,
Sports, Science and Technology, Japan and the Kurata
Memorial Hitachi Science and Technology Foundation.
11 Oxidative coupling of an imine with a rhodium complex to form an
isoquinolium salt: L. Li, W. W. Brennessel and W. D. Jones, J. Am.
Chem. Soc., 2008, 130, 12414.
12 For recent examples, see: (a) J. H. Ahn, M. S. Shin, S. H. Jung,
J. A. Kim, H. M. Kim, S. H. Kim, S. K. Kang, K. R. Kim, S. D. Rhee,
S. D. Park, J. M. Lee, J. H. Lee, H. G. Cheon and S. S. Kim, Bioorg.
Med. Chem. Lett., 2007, 17, 5239; (b) K. Y. Kim, S. S. Kim and
H. G. Cheon, Biochem. Pharmacol., 2006, 72, 530; (c) K. R. Kim,
J. H. Lee, S. J. Kim, S. D. Rhee, W. H. Jung, S.-D. Yang, S. S. Kim,
J. H. Ahn and H. G. Cheon, Biochem. Pharmacol., 2006, 72, 446;
(d) F. Churruca, R. SanMartin, M. Carril, M. K. Urtiaga, X. Solans,
I. Tellitu and E. Domınguez, Org. Lett., 2005, 70, 3178.
´
Notes and references
13 A similar mechanism involving successive insertion of an alkyne
and an imino moiety has been proposed for the Re-catalyzed non-
oxidative coupling of imines with alkynes: (a) Y. Kuninobu,
Y. Tokunaga, A. Kawata and K. Takai, J. Am. Chem. Soc.,
2006, 128, 202; (b) Y. Kuninobu, A. Kawata and K. Takai,
J. Am. Chem. Soc., 2005, 127, 13498.
1 For recent reviews concerning C–H bond functionalization, see:
(a) F. Kakiuchi and T. Kochi, Synthesis, 2008, 3013; (b) J. C. Lewis,
R. G. Bergman and J. A. Ellman, Acc. Chem. Res., 2008, 41, 1013;
(c) A. Mori and A. Sugie, Bull. Chem. Soc. Jpn., 2008, 81, 548;
(d) E. M. Ferreira, H. Zhang and B. M. Stoltz, Tetrahedron, 2008,
ꢁc
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Chem. Commun., 2009, 5141–5143 | 5143