Rhodium-catalyzed intermolecular [4+2] cycloaddition of unactivated substrates

Full text of DOI:10.1002/(SICI)1521-3773(19980904)37:16<2248::AID-ANIE2248>3.0.CO;2-1

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�
3
1
calcd ˆ 1.383 gcm , F(000) ˆ 2256, MoKa (l ˆ 0.71069 Š, m(MoKa) ˆ
substituted benzene derivatives can be synthesized in a highly
regioselective manner.
�
1
4
.38 cm : crystal dimensions 0.23 Â 0.29 Â 0.34 mm. For 2505 unique
observed reflections [I > 2s(I)] collected at Tˆ 295 K on a Rigaku
We first examined the reaction of vinylallene 1a with the
unactivated dienophile 1-hexyne in the presence of
[Rh(dppe)(cod)]PF6 (dppe ˆ 1,2-bis(diphenylphosphanyl)-
ethane, cod ˆ (Z,Z)-1,5-cyclooctadiene), a potent catalyst
for the [4‡1] cycloaddition of vinylallene with carbon
monoxide.[ However, [4‡2] cycloaddition failed to occur
AFC6S diffractometer (6 < 2q < 508) the conventional R value is 0.026
(
wR2 ˆ 0.043 for the 4570 unique reflections having I > 0 used in the
refinement). Crystallographic data (excluding structure factors) for
the structures reported in this paper have been deposited with the
Cambridge Crystallographic Data Center as supplementary publica-
tion no. CCDC-101526 . Copies of the data can be obtained free of
charge on application to CCDC, 12 Union Road, Cambridge
CB21EZ, UK (fax: (‡44)1223-336-033; e-mail: deposit@ccdc.cam.
ac.uk).
5a]
[8]
even under forcing conditions, which led us to examine the
electronic perturbation of the catalyst.[ Screening of various
combinations of catalyst precursors and phosphorus ligands
under different reaction conditions revealed that a complex
9]
[
[
11] a) A. F. Wells, Structural Inorganic Chemistry 5th ed., Oxford
University Press, Oxford, 1986, p. 344; b) ibid. p. 534.
12] The synthesis and structure of [Me N Na (thf) ] will be reported in a
8 4 4 2
prepared in situ from [Rh(cod) ]OTf and P[OCH(CF ) ] , one
forthcoming paper. The alternative use of the sodium instead of the
lithium porphyrinogen is dictated by easier separation of NaCl from
the reaction mixture.
2
3 2 3
of the most strongly electron-accepting ligands available,
[10]
efficiently catalyzed the [4‡2] cycloaddition.
1,2-Dime-
thoxyethane (DME) was the solvent of choice. Thus, a
mixture of 1a, 1-hexyne (2 equiv), [Rh(cod) ]OTf
2
(
5 mol%), and P[OCH(CF ) ] (5 mol%) in DME was heated
3 2 3
at 508C for 24 h (Scheme 1). Isomerization (i.e. aromatiza-
tion) ensued after cycloaddition to afford the corresponding
tetrasubstituted benzene in 70% yield as a mixture of
regioisomers (2a and 2b).
Rhodium-Catalyzed Intermolecular [4‡2]
Cycloaddition of Unactivated Substrates**
Masahiro Murakami,* Minoru Ubukata, Kenichiro
Itami, and Yoshihiko Ito*
Cycloaddition reactions have played a prominent role in
[
1]
the construction of complex cyclic compounds. In particular,
4‡2] Diels ± Alder cycloaddition is arguably the most im-
portant synthetic tool for the preparation of six-membered
[
[
2]
rings. Virtually the only requirement for [4‡2] cycloaddition
reactions to be effective is that the two components have
complementary electronic properties. This is typically ach-
ieved by employing an electron-rich 1,3-diene and an elec-
tron-deficient dienophile. In fact, 1,3-dienes and dienophiles
in which the multiple bonds are not activated by electron-
withdrawing or electron-releasing substituents fail to undergo
cycloaddition except under the most severe conditions. The
use of transition metal catalysts has proven to be a valuable
solution to this limitation. Complexation of unactivated
Scheme 1. [4‡2] Cycloaddition of vinylallene 1a with 1-hexyne.
A variety of substrates were allowed to react under the
standard reaction conditions to produce the corresponding
aromatic compounds (Table 1).[
11]
It is noteworthy that
[
3]
synthetically useful results were obtained with substrates
lacking directive heteroatom functionalities. For example,
ethyne was found to be a reactive dienophile. Furthermore,
when a terminal alkyne and a vinylallene lacking substituents
at the vinylic terminus were used, 1,3,5-trisubstituted benzene
substrates to such catalysts promotes both inter- and intra-
[
4]
molecular [4‡2] cycloadditions. Recently, we developed
new [4‡1] and [4‡2] cycloaddition reactions of unactivated
vinylallenes based on our study of their bonding interactions
[
5±7]
with transition metals.
Here we report a rhodium-cata-
derivatives (2d, 2 f ± j) were produced in a highly regioselec-
lyzed intermolecular [4‡2] cycloaddition reaction between a
vinylallene and an ordinary alkyne which proceeds under mild
conditions without the need for electron-withdrawing or
electron-releasing substituents. With this method, 1,3,5-tri-
tive manner.[
12]
Hydroxyl and chloro functionalities are
compatible with the present reaction conditions (2h, 2i). In
the case of 1,7-octadiyne, a tethered bis-benzene derivative
(
2j) was obtained in 82% yield, without formation of the
[13]
[2‡2‡2] cycloadduct.
An internal alkyne could also be
[
*] Prof. M. Murakami, Prof. Y. Ito, M. Ubukata, K. Itami
Department of Synthetic Chemistry and Biological Chemistry
Kyoto University
employed in the reaction. Vinylallenes in which the allenic
terminus is monosubstituted (1d) and nonsubstituted (1e)
gave lower yields of the corresponding cycloadducts (2l, 2m).
These results can be explained in terms of the preference for
Yoshida, Kyoto 606 ± 8501 (Japan)
Fax: (‡81)75-753-5668
**] Support from Monbusho is gratefully acknowledged. K.I. thanks the
Japan Society for the Promotion of Science for a predoctoral
fellowship.
2
4
2
h over h coordination. With 1d and 1e, h coordination at the
allenic p bond distal to the vinyl group would be favored over
h coordination owing to steric reasons.
[
4
[5a, 14]
2
248
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Angew. Chem. Int. Ed. 1998, 37, No. 16

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Table 1. [4‡2] Cycloaddition of vinylallenes with alkynes.
Vinylallene
Alkyne
Amount of
alkyne
T[8C]
t[h]
Product
Yield[%][a]
6
1
a
10 Pa
20
16
93
2
1
equiv
20
3
87
06 Pa
20
20
16
2
81
84
1
c
1.5 equiv
1
1
c
c
2equiv
2 equiv
70
70
40
72
48
55[b]
1
1
c
c
2 equiv
2equiv
20
20
4
4
94
93
1
1
c
c
0
.3equiv
70
60
23
13
82[b, c]
1.3equiv
65[d]
5
5
equiv
equiv
20
20
48
96
24
15
[
a] Yield of isolated product based on 1. [b] 2 equiv of P[OCH(CF
3
)
2
]
3
based on Rh. [c] Yield of isolated product based on 1,7-octadiyne. [d] 5 equiv of
P[OCH(CF based on Rh.
3 2 3
) ]
Under the present conditions, even ethene, one of the most
sluggish dienophiles, underwent cycloaddition with 1c to give
cyclohexene 3 at temperatures as low as 208C, albeit in low
yield (33%, Scheme 2).
A plausible mechanism for the production of 2 is shown in
Scheme 3. A five-membered rhodacycle is initially formed
from the vinylallene substrate.[5a, b] After coordination of the
alkyne to the rhodium center, C ± C bond formation takes
place to afford a seven-membered rhodacycle. The regio-
chemical outcome observed with terminal alkynes can be
regarded as a consequence of the selective formation of 4 by
insertion of an alkyne into the Rh ± Csp
3
bond. Competing
Angew. Chem. Int. Ed. 1998, 37, No. 16
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1433-7851/98/3716-2249 $ 17.50+.50/0 2249

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s, 1H), 6.87 (s, 1H); 13C{ H} NMR (75 MHz, CDCl
1
): d ˆ 14.0, 14.7, 20.8,
(
2
3
2.9, 24.1, 33.0, 33.6, 34.0, 125.0, 125.5, 131.7, 136.6, 140.9, 145.7. Elemental
analysis calcd for C15
H
24 (204.36): C 88.16, H 11.84; found: C 87.91, H 11.72.
Received: March 12, 1998 [Z11581IE]
German version: Angew. Chem. 1998, 110, 2362 ± 2364
Keywords: alkynes ´ cycloadditions ´ P ligands ´ rhodium ´
6
vinylallenes
Scheme 2. [4‡2] Cycloaddition of vinylallene 1c with ethene (2  10 Pa).
[1] W. Carruthers, Cycloaddition Reactions in Organic Synthesis, Perga-
mon, Oxford, 1990, pp. 1 ± 208.
[2] W. Oppolzer in Comprehensive Organic Synthesis, Vol. 5 (Eds.: B. M.
Trost, I. Fleming, L. A. Paquette), Pergamon, Oxford, 1991, pp. 315 ±
3
99.
[3] a) A. Carbonaro, A. Greco, G. DallꢁAsta, J. Org. Chem. 1968, 33, 3948;
b) H. Siegel, H. Hopf, A. Germer, P. Binger, Chem. Ber. 1978, 111,
3
112; c) H. tom Dieck, R. Diercks, Angew. Chem. 1983, 95, 801;
Angew. Chem. Int. Ed. Engl. 1983, 22, 778; d) I. Matsuda, M. Shibata,
S. Sato, Y. Izumi, Tetrahedron Lett. 1987, 28, 3361; e) S. Saito, M. M.
Salter, V. Gevorgyan, N. Tsuboya, K. Tando, Y. Yamamoto, J. Am.
Chem. Soc. 1996, 118, 3970; f) V. Gevorgyan, A. Takeda, Y.
Yamamoto, ibid. 1997, 119, 11313.
[4] a) P. A. Wender, T. E. Jenkins, J. Am. Chem. Soc. 1989, 111, 6432;
b) R. S. Jolly, G. Luedtke, D. Sheehan, T. Livinghouse, ibid. 1990, 112,
4
965; c) T. Mandai, S. Suzuki, A. Ikawa, T. Murakami, M. Kawada, J.
Scheme 3. Proposed mechanism of the rhodium-catalyzed [4‡2] cyclo-
Tsuji, Tetrahedron Lett. 1991, 32, 7687; d) L. McKinstry, T. Living-
house, Tetrahedron 1994, 50, 6145; e) P. A. Wender, T. E. Jenkins, S.
Suzuki, J. Am. Chem. Soc. 1995, 117, 1843; f) P. A. Wender, T. E.
Smith, J. Org. Chem. 1995, 60, 2962; g) D. J. R. OꢁMahony, D. B.
Belanger, T. Livinghouse, Synlett 1998, 443.
5] a) M. Murakami, K. Itami, Y. Ito, Angew. Chem. 1995, 107, 2943;
Angew. Chem. Int. Ed. Engl. 1995, 34, 2691; b) J. Am. Chem. Soc. 1996,
118, 11672; c) ibid. 1997, 119, 2950; d) ibid. 1997, 119, 7163.
6] For other examples of cycloaddition of vinylallenes, see a) M. S.
Sigman, B. E. Eaton, J. Am. Chem. Soc. 1996, 118, 11783; b) T.
Mandai, J. Tsuji, Y. Tsujiguchi, ibid. 1993, 115, 5865; c) C. Darcel, C.
Bruneau, P. H. Dixneuf, Synlett 1996, 218; d) see also ref. [3b, 4c].
[7] For other examples of vinylallene complexes, see C. E. Kerr, B. E.
Eaton, J. A. Kaduk, Organometallics 1995, 14, 269, and references
therein.
addition; a) reductive elimination, b) aromatization.
formation of a seven-membered rhodacycle with the alter-
native alkyne orientation (5) would be disfavored because of
repulsive steric interactions between the alkyne substituent R2
and the ligands on the metal. This interpretation also accounts
for the nonregioselective cyclization of 1a; the preference for
an intermediate analogous to 4 would be balanced due to an
additional steric interaction between the alkyne substituent
[
[
2
[15]
R and the methyl group at the vinylic terminus of 1a.
Finally, reductive elimination followed by isomerization
completes the formation of the substituted arenes.
[
8] The palladium(0) complex [Pd(PPh
3 4
) ] which successfully promoted
In summary, intermolecular [4‡2] cycloaddition reactions
of vinylallenes with alkynes, without the necessity of activa-
ting heteroatoms, is successfully mediated by use of an
electronically tuned rhodium catalyst. Although the precise
reason of the beneficial effect of employing an electron-
accepting ligand is unclear, the present work indicates that
optimization of a ligand set by electronic tuning will offer
great potential for the regulated incorporation of unreactive
substances, including readily available carbon feedstocks such
as ethene and ethyne, into carbon skeletons.
the intermolecular [4‡2] cycloaddition between vinylallene and 1,3-
[5d]
diene was ineffective for the reaction of 1a with 1-hexyne.
[9] a) P. W. N. M. van Leeuwen, C. F. Roobeek, Tetrahedron, 1981, 37,
973; b) P. W. N. M. van Leeuwen, C. F. Roobeek, J. Organomet.
1
Chem. 1983, 258, 343.
[
10] For the acceleration of cycloaddition reactions by the use of electron-
accepting phosphite ligands, see references [4b, d ± g]. In the present
cycloaddition, electron-accepting P[OCH(CF ) ] might facilitate
3
2 3
reductive elimination of 4 in Scheme 3.
3 2 3
11] The use of two or more equivalents of P[OCH(CF ) ] (based on
[
rhodium) gave better yields of 2 in some cases, especially when
heating was required.
[
[
[
12] The stereochemistries were determined by 1H NMR NOE studies.
13] R. Grigg, R. Scott, P. Stevenson, Tetrahedron Lett. 1982, 23, 2691.
14] M. Murakami, K. Itami, M. Ubukata, I. Tsuji, Y. Ito, J. Org. Chem.
1998, 63, 4.
Experimental Section
2
a
and 2b:
A
mixture of [Rh(cod)
2
]OTf (9.6 mg, 20.5 mmol),
P[OCH(CF
3
)
2
]
3
(10.9 mg, 20.5 mmol), 1a (50.0 mg, 409 mmol), and 1-
[15] The nonregioselective reaction with 1a is hardly explained by
hexyne (67.2 mg, 818 mmol) in DME (2 mL) was stirred at 508C for 24 h.
assuming insertion of an alkyne into the Rh ± Csp2 bond.
After the mixture was cooled, the solvent was removed under vacuum. The
residue was subjected to gel permeation chromatography to afford a
1
mixture of 2a and 2b (58.2 mg, 70%). 2a: H NMR (300 MHz, CDCl
0
3
): d ˆ
.94 (t, J ˆ 7.3 Hz, 3H), 1.22 (d, J ˆ 6.8 Hz, 6H), 1.35 ± 1.45 (m, 2H), 1.48 ±
1
.58 (m, 2H), 2.20 (s, 3H), 2.23 (s, 3H), 2.57 (t, J ˆ 7.9 Hz, 2H), 3.11 (septet,
1
3
1
J ˆ 6.8 Hz, 1H), 6.90 (s, 1H), 7.01 (s, 1H); C{ H} NMR (75 MHz, CDCl
3
):
d ˆ 14.0, 19.2, 19.5, 22.9, 24.2, 28.2, 32.2, 34.3, 126.5, 130.8, 133.4, 134.0,
1
1
1
37.0, 143.8. 2b: H NMR (300 MHz, CDCl
3
): d ˆ 0.95 (t, J ˆ 7.3 Hz, 3H),
.23 (d, J ˆ 6.8 Hz, 6H), 1.35 ± 1.45 (m, 2H), 1.48 ± 1.58 (m, 2H), 2.16 (s,
3
H), 2.27 (s, 3H), 2.60 (t, J ˆ 7.7 Hz, 2H), 2.81 (septet, J ˆ 6.8 Hz, 1H), 6.86
2
250
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