Iridium complex-catalyzed cross-coupling reaction of terminal alkynes with internal alkynes via C-H activation of terminal alkynes

Article abstract of DOI:10.1002/adsc.200404359

The cross-dimerization of an electron-rich terminal alkyne with an electron-deficient internal alkyne was promoted by an iridium complex to produce a 1:1 adduct in high regio- and stereoselectivities. This reaction was extended to various combinations of

Full text of DOI:10.1002/adsc.200404359

FULL PAPERS
Iridium Complex-Catalyzed Cross-Coupling Reaction of Terminal
ꢀ
Alkynes with Internal Alkynes via C H Activation of Terminal
Alkynes
Tomotaka Hirabayashi, Satoshi Sakaguchi, Yasutaka Ishii*
Department of Applied Chemistry, Faculty of Engineering, Kansai University, Suita, Osaka 564-8680, Japan
Fax: (þ81)-6-6339-4026, e-mail: ishii@ipcku.kansai-u.ac.jp
Received: November 25, 2004; Accepted: March 8, 2005
Supporting Information for this article is available on the WWW under http://asc.wiley-vch.de/home/.
Abstract: The cross-dimerization of an electron-rich the 1:2 cross-cyclotrimerization reaction took place
terminal alkyne with an electron-deficient internal al- to form substituted benzene derivatives. A plausible
kyne was promoted by an iridium complex to produce reaction path was suggested based on a labeling ex-
a 1:1 adduct in high regio- and stereoselectivities. periment. This reaction provides a method for the
This reaction was extended to various combinations production of complicated enynes which are difficult
of terminal alkynes with internal alkynes such as al- to be prepared by conventional methods.
kynyl esters and alkynyl aldehydes. The selectivity
ꢀ
of the reaction was found to markedly depend on Keywords: alkynes; C H activation; catalysis; cross-
the ligands used. When dppe was used as a ligand, coupling; dimerization; iridium complex
Introduction
lyst,[9] we have now found that terminal alkynes add se-
lectively to activated internal alkynes in the presence of
ꢀ
The C C bond-forming reaction is one of the most im- a catalytic amount of [IrCl(cod)]2 combined with biden-
portant reactions in organic synthesis. In particular, tate ligands such as (rac)-BINAP, 1,4-bis(diphenylphos-
the dimerization of alkynes is a very useful method for phino)butane (dppb) and 1,1’-bis(diphenylphosphino)-
forming compounds such as enynes from simple al- ferrocene (dppf).
kynes.[1] Transition metal-catalyzed coupling reactions
of alkynes constitute an effective method for forming
synthetically useful compounds.[2] However, the catalyt- Results and Discussion
ic intermolecular dimerization of alkynes has not yet
been developed,[3] since the homo- and cross-dimeriza- In the first place, we examined the cross-addition of 1-
tions of two different alkynes take place simultaneously octyne (1a) with methyl phenylpropiolate (2a) using
to result in a complex mixture of products like homo- [IrCl(cod)]2 (cod¼cycloocta-1,5-diene) combined with
dimers,[4] trimers, [5] and oligomers in addition to the de- various phosphines [Eq. (1) and Table 1].
sired cross-dimers. Trost et al. have reported the selec-
tive cross-addition of terminal alkynes (donor alkynes)
to activated internal alkynes (acceptor alkynes) by the
use of palladium acetate in the presence of an elec-
tron-rich, sterically encumbered ligand like tris(2,6-di-
methoxyphenyl)phosphine.[6] Quite recently, Yi and
co-worker have reported a similar cross-dimerization
of unactivated internal alkynes using a ruthenium-vinyl-
idene complex as the catalyst.[7] Furthermore, there
have been several studies on the synthesis of enyne com-
pounds from halogenated alkenes and alkynes catalyzed
ð1Þ
by a Cu complex and from alkynes and a stoichiometric A typical reaction was carried out as follows. To a solu-
amount of a Ti complex.[8]
tion containing [IrCl(cod)]2 (0.035 mmol) and dppb
In the course of our studies to develop a new coupling (0.07 mmol) in toluene was added a 1:1 mixture of 1a
reaction of alkynes using an iridium complex as a cata- (0.5 mmol) and 2a (0.5 mmol). The reaction was carried
872
ꢀ 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
DOI: 10.1002/adsc.200404359
Adv. Synth. Catal. 2005, 347, 872–876

Ir-Catalyzed Cross-Coupling of Terminal Alkynes with Internal Alkynes
FULL PAPERS
Table 1. The cross-dimerization of 1a with 2a catalyzed by [IrCl(cod)]2 under various conditions.[a]
Entry
Ir Complex
Ligand
Conversion [%][b]
Yield [%][c]
1
2
3
4
5
6
7
8
9
[IrCl(cod)]2
[IrCl(cod)]2
[IrCl(cod)]2
[IrCl(cod)]2
[IrCl(cod)]2
[IrCl(cod)]2
[IrCl(cod)]2
[Ir(cod)2]þBF4
IrCl3
dppb
none
PPh3
PCy3
P(OBu-n)3
dppf
(rac)-BINAP
(rac)-BINAP
(rac)-BINAP
69
8
48
89
3
>99
>99
4
35
9
n.d.
2
n.d.
n.d.
12
n.d.
<1
n.d.
<1
62
83
n.d.
2
n.d.
ꢀ
No reaction
[a]
Alkyne 1a (0.5 mmol) was reacted with 2a (0.5 mmol) in the presence of [IrCl(cod)]2 (0.035 mmol) and ligand (0.07 mmol)
in toluene (1 mL) at 808C for 3 h.
The conversion was based on 2a.
The yield was based on 2a used.
[b]
[c]
Table 2. The cross-dimerization of two different monoynes
out at 808C for 3 h, giving a regioisomeric mixture of
cross-addition products, 3aa (35%) and 4aa (9%) (Entry
1). In the absence of a ligand, most of 2a was recovered
(Entry 2). Monodentate phosphines, PPh3 and PCy3, and
phosphite P(OBu-n)3, resulted in 3aa in poor yields (En-
tries 3 to 5), while the reaction using a bidentate phos-
phine like dppf gave 3aa in fair yield (62%) (Entry 6).
When (rac)-BINAP was employed as a ligand, 3aa was
produced in the highest yield (83%) (Entry 7). This is
the first successful 1:1 cross-addition of alkynes cata-
lyzed by iridium complexes. The cationic iridium com-
catalyzed by [IrCl(cod)]2.[a]
plex [Ir(cod)2]þBF4 and IrCl3 were inert in this reac-
ꢀ
tion (Entries 8 and 9).
On the basis of these results, the cross-dimerization of
various terminal alkynes (1b–f) with internal alkynes
was examined [Eq. (2) and Table 2].
ð2Þ
[a]
Alkyne 1 (0.5 mmol) was reacted with 2 (0.5 mmol) in the
presence of [IrCl(cod)]2 (0.035 mmol) and (rac)-BINAP
(0.07 mmol) in toluene (1 mL) at 808C for 3 h.
[b] The yield was based on 2 used, and the number in parenth-
esis shows the E/Z ratio.
Trimethylsilylacetylene (1b), phenylacetylene (1c), tert-
butyl 1-methyl-2-propynyl ether (1d) and 1-ethynyl-1-
cyclohexanol (1e) reacted with 2a under these condi-
tions to give the corresponding cross-addition products,
3ba, 3ca, 3da and 3ea, respectively, in fair to good yields
(Entries 1 to 4). The reaction of methyl propiolate (1f) as
the electron-deficient terminal alkyne with 2a did not
form a cross-adduct, but rather afforded small amounts
of the cyclotrimerization products of 1f, trimethyl 1,2,4-
[c]
Dppf was used instead of (rac)-BINAP.
Dppb was used instead of (rac)-BINAP.
3-(3-tert-Butoxybut-1-ynyl)-oct-3-enal (5dd) was obtained
[d]
[e]
in 22% yield.
[f]
See text.
and 1,3,5-benzenecarboxylates (7) (Entry 5). When 1a try 6). The reaction of 1c with 2b and 1d with 2c provided
was allowed to react with 2b under the standard condi- the corresponding cross-adducts 3cb (57%) and 3dc
tions, the desired product (3ab) consisting of a 1:1 mix- (62%), respectively (Entries 7 and 8). Alyknyl ether 1d
ture of E- and Z-isomers was obtained in 56% yield (En- reacted with alkynyl aldehyde (2d), giving 3dd (32%)
Adv. Synth. Catal. 2005, 347, 872–876
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Tomotaka Hirabayashi et al.
FULL PAPERS
along with 3-(3-tert-butoxybut-1-ynyl)-oct-3-enal (5dd) phenylacetylene-d1 (1c-d1) with 2a. The 1H NMR spec-
(22%) (Entry 9). The reaction of 1a with diphenylacety- trum of the resulting product showed that the reaction
lene (2e) formed a 1:1 cross-adduct 3ae in low yield cleanly proceeded with almost complete selectivity to
(16%) (Entry 10). However, dimethyl acetylenedicar- form mono-deuterio cross-adduct 3ca-d1 [Eq. (4), Fig-
boxylate (2f) reacted with 1a to give the [2þ2þ2] cyclo- ure 1].
trimerization product (6af) of 1a:2f¼1:2 in 38% yield,
but not the desired product 3af (Entry 11). Recently,
Takeuchi and co-workers have reported the iridium-cat-
alyzed the [2þ2þ2] cyclotrimerizations of 1c and 2f.[10]
We found that the cross-cyclotrimerization is also pro-
moted by [IrCl(cod)]2 by the use of dppe as a ligand in
the presence of a small amount of Na2CO3 under mild
conditions [Eq. (3)].
ð4Þ
These results suggest that the reaction proceeds via the
following reaction pathway (Scheme 1). First, the oxida-
tive addition of terminal alkyne 1c-d1 to an iridium com-
ð3Þ
plex leads to an alkynyl-iridium complex (A). The coor-
In order to obtain mechanistic information about the dination of an internal alkyne (2a) to A followed by in-
present cross-addition, we attempted the reaction of sertion gives a vinyliridium complex (C). The oxidative
Figure 1. 1H NMR spectrum of the product from the reaction of 1c-d1 with 2a.
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Adv. Synth. Catal. 2005, 347, 872–876

Ir-Catalyzed Cross-Coupling of Terminal Alkynes with Internal Alkynes
FULL PAPERS
Procedure for the Cyclotrimerization of 1a and Methyl
Propiolate (2f)
To a solution containing [IrCl(cod)]2 (0.05 mmol), dppe
(0.1 mmol) and Na2CO3 (0.1 mmol) in toluene (2 mL) was add-
ed a 2:1 mixture of 1a (2 mmol) and 2f (1 mmol). The reaction
was carried out at 608C for 15 h. Removal of the solvent under
reduced pressure afforded a cloudy solution, which was puri-
fied by column chromatography on silica gel (n-hexane/ethyl
acetate¼9/1) to give the corresponding product. The products
were characterized by 1H and 13C NMR, IR, and GC-MS, re-
spectively.
Supporting Information
Characterization data for products 3.
Scheme 1. A plausible reaction pathway for the cross-dimeri-
zation of alkynes.
addition of alkyne to C followed by reductive elimina- Acknowledgements
tion produces the enyne 3ca-d1, and the complex A
This work was partially support by a Grant-Aid for Scientific
may be regenerated.
Research (KAKENHI) (S) (No. 13853008) from Japan Society
for the Promotion of Science (JSPS), and DAICEL Chemical
Industries, Ltd.
Conclusion
We have found a catalytic cross-dimerization between
terminal alkynes and internal alkynes, catalyzed by an
iridium complex. This reaction provides a method for
the production of various complicated enyne com-
pounds.
References and Notes
[1] a) B. M. Trost, Angew. Chem. Int. Ed., 1995, 34, 259;
b) B. M. Trost, Science 1991, 254, 1471.
[2] Recent reviews: a) G. W. Parshall, S. D. Ittel, Homogene-
ous Catalysis, 2nd edn., Wiley: New York, 1992; b) H.
Bçnnemann, W. Brijoux, in: Applied Homogeneous Cat-
alysis with Organometallic Compounds, (Eds.: B. Cornils,
W. A. Herrmann), VCH, New York, 1996, Vol. 2, p. 1102;
c) N. E. Schore, in: Comprehensive Organic Synthesis,
(Ed.: B. M. Trost), Pergamon Press: New York, 1990,
Vol. 5.
Experimental Section
General Remarks
1H and 13C NMR were measured at 270 and 67.5 MHz, respec-
tively, in CDCl3 with TMS as the internal standard. Infrared
(IR) spectra were measured as thin films on NaCl plate or
KBr pressed disks. GLC analysis was performed with a flame
ionization detector using a 0.2 mmꢁ25 m capillary column
(OV-17). Mass spectra were determined at an ionizing voltage
of 70 eV. All starting materials, catalysts, and initiators were
purchased from commercial sources and used without further
treatment. The yields of products were estimated from the
peak areas based on the internal standard technique.
[3] D. B. Grotjahn, in: Comprehensive Organometallic
Chemistry II, (Eds.: E. W. Abel, F. G. A. Stone, G. Wil-
kinson), Pergamon Press: New York, 1994, Vol. 12.
[4] For Ru: a) Y. Wakatsuki, H. Yamazaki, N. Kumegawa, T.
Satoh, J. Y. Satoh, J. Am. Chem. Soc. 1991, 113, 9604;
b) C. Bianchini, M. Peruzzini, F. Zanobini, P. Frediani,
A. Albinati, J. Am. Chem. Soc. 1991, 113, 5453; c) Y. Sa-
saki, P. H. Dixneuf, J. Chem. Soc. Chem. Commun. 1986,
790 and references cited therein; for Rh: d) M. Schꢁfer,
N. Mahr, J. Wolf, H. Werner, Angew. Chem. Int. Ed.
1993, 32, 1315; e) W. T. Boese, A. S. Goldman, Organo-
metallics 1991, 10, 782; for Ni: f) M. Ishikawa, J. Ohshita,
Y. Ito, A. Minato, J. Chem. Soc. Chem. Commun. 1988,
804; for Pd: g) F. A. Selimov, O. G. Rutman, U. M. Dzhe-
milev, J. Organomet. Chem. 1988, 346, C58; for Cu: h) M.
Rubina, V. Gevorgyan, J. Am. Chem. Soc. 2001, 123,
11107; for Ir: i) T. Ohmura, S. Yorozuya, Y. Yamamoto,
N. Miyaura, Organometallics 2000, 19, 365; others:
j) A. K. Dash, M. S. Eisen, Org. Lett. 2000, 2, 737; k) T.
Straub, A. Haskel, M. S. Eisen, J. Am. Chem. Soc.
Typical Procedure for the Cross-Coupling of 1-Octyne
(1a) and Methyl Phenylpropiolate (2a)
To a solution containing [IrCl(cod)]2 (0.035 mmol) and dppb
(0.07 mmol) in toluene (1 mL) was added a 1:1 mixture of 1a
(0.5 mmol) and 2a (0.5 mmol). The reaction was carried out
at 808C for 3 h. Removal of the solvent under reduced pressure
afforded a cloudy solution, which was purified by column chro-
matography on silica gel (n-hexane/ethyl acetate¼10/1) to
give the corresponding product. The products were character-
ized by 1H and 13C NMR, IR, and GC-MS, respectively.
Adv. Synth. Catal. 2005, 347, 872–876
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Tomotaka Hirabayashi et al.
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1995, 117, 6364; l) M. Nishiura, Z. Hou, J. Mol. Catal. A:
Chemical, 2004, 213, 101.
Yamazaki, Y. Liu, K. Nakajima, M. Kotora, J. Am.
Chem. Soc. 1998, 120, 1672.
[5] For no catalyst: a) K. P. C. Vollhardt, Angew. Chem. Int.
Ed. Engl. 1984, 23, 539; b) L. D. Field, A. Ward, Aust. J.
Chem. 1999, 52, 1085; for Ni: c) Y. Sato, T. Nishimata,
M. Mori, J. Org. Chem., 1994, 59, 6133; for Rh: d) F. E.
McDonald, H. Y. H. Zhu, C. R. Holmquist, J. Am.
Chem. Soc. 1995, 117, 6605; e) R. Witulski, T. Stengel,
Angew. Chem. Int. Ed. Engl. 1999, 38, 2426; for Pd:
f) Y. Yamamoto, A. Nagata, Y. Arikawa, K. Tatsumi,
K. Itoh, Organometallics, 2000, 19, 2403; for Ru: g) J.-
U. Peters, S. Blechert, Chem. Commun. 1997, 1983;
h) Y. Yamamoto, R. Ogawa, K. Itoh, Chem. Commun.
2000, 549; for Ir: i) R. Takeuchi, Synlett 2002, 12, 1954;
j) C. Bianchini, K. G. Caulton, C. Chardon, O. Eisen-
stein, K. Folting, T. J. Johnson, A. Meli, M. Peruzzini,
D. J. Rauscher, W. E. Streib, F. Vizza, J. Am. Chem.
Soc. 1991, 113, 5127; for Zr: k) T. Takahashi, Z. Xi, A.
[6] a) B. M. Trost, C-J. Li, Synthesis 1994, 1267; b) B. M.
Trost, M. C. McIntosh, J. Am. Chem. Soc. 1995, 117,
7255; c) B. M. Trost, M. T. Sorum, C. Chan, A. E. Harms,
G. Rhter J. Am. Chem. Soc. 1997, 119, 698; d) B. M.
Trost, A. J. Frontier, J. Am. Chem. Soc. 2000, 122, 11727.
[7] C. S. Yi, N. Liu, Organometallics 1998, 17, 3158.
[8] a) T. Mandai, Y. Tsujiguchi, S. Matsuoka, J. Tsuji, Tetra-
hedron Lett. 1993, 34, 7615; b) U. Lcking, A. Pfaltz, Syn-
lett 2000, 1261; c) C. Delas, H. Urabe, F. Sato, Chem.
Commun. 2002, 272; d) C. G. Bates, P. Saejueng, D. Ven-
kataraman, Org. Lett. 2004, 6, 1441.
[9] a) Y. Ishii, S. Sakaguchi, Bull. Chem. Soc. Jpn. 2004, 77,
909; b) S. Sakaguchi, T. Kubo, Y. Ishii, Angew. Chem.
Int. Ed. 2001, 40, 2534.
[10] R. Takeuchi, Y. Nakaya, Org. Lett. 2003, 5, 3659.
876
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