Full text of DOI:10.1016/S0040-4039(00)01378-2

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 7905–7909
Reaction of (cycloalkenyl)alkylzirconium compounds with
alkynes: novel procedure for the formation of bicyclic
compounds
Martin Kotora,a Guohua Gao,a Zhiping Li,b Zhenfeng Xib and Tamotsu Takahashia,*
aCatalysis Research Center and Graduate School of Pharmaceutical Sciences, Hokkaido University, and CREST,
Science and Technology Corporation (JST), Sapporo 060-0811, Japan
bPeking Univ.-Hokkaido Univ. Joint Lab., Department of Chemistry, Peking University, Beijing 100871, China
Received 10 April 2000; revised 7 August 2000; accepted 10 August 2000
Abstract
Reaction of (cycloalkenyl)alkyl zirconium compounds with alkynes in the presence of MAO afforded
bicyclic tetrahydroindene derivatives with a methyl group at the ring junction. © 2000 Elsevier Science
Ltd. All rights reserved.
Keywords: zirconium; alkyne; MAO; cyclization.
The reactions of zirconium cationic species with unsaturated bonds have received considerable
attention in recent years, and both alkyl- and alkenylzirconium cationic species were shown to
react with alkenes and alkynes as well as with a carbonyl group under different conditions.1 For
example, cationic alkylzirconium compounds are very efficient catalysts for alkene polymeriza-
tion,1 cationic zirconium complexes generated by the reaction of alkyl- or alkenylchloro-
zirconocenes with AgClO4 or similar salts reacted with aldehydes to give saturated secondary
and secondary allylic alcohols,2 cationic zirconium complexes formed by the reaction of
Cp2ZrCl2 and MAO3 or Cp*2ZrMe2 and B(C6F5)3 with excess of Me3Al4 cyclize 1,5-, 1,6-,
1,7-dienes to the corresponding five-, six, and seven-membered ring compounds. Recently, it has
also been shown that alkyl- and allylchlorozirconium complexes reacted in the presence of a
catalytic amount of [(C6H5)3C]+[B(C6F5)4]− or MAO with carbonꢀcarbon triple bonds to give
functionalized alkenes.5
During our research of cyclization reactions by means of zirconocene derivatives we realized
that it would be of interest to develop a reaction sequence capable of constructing a bicyclic
framework in one step from easily accessible starting material. While studying cyclization
reactions of 2-chloro-1,v-dienes, prepared by double allylation of alkynes,6 with the Negishi
* Corresponding author. Fax: +81-11-706-3274; e-mail: tamotsu@cat.hokudai.ac.jp
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01378-2

7906
reagent to give 1-methylene-2-methylcycloalkanes, as it was initially reported by us7 and later by
others,8 we came to the conclusion that the intermediate organozirconium compound 1 could be
utilized in subsequent CꢀC bond formation reactions with alkenes and alkynes followed by
intramolecular cyclization with the participation of the exo double bond to give 5–6 or 6–6 fused
bicyclic compounds (Eq. 1).
(1)
Herein, we would like to present a novel method for the formation of bicyclic compounds
based on the reaction of (cycloalkenyl)alkylzirconium compounds 1 with terminal alkynes.
Typically, organozirconium compound 1, prepared by the reaction of the Negishi reagent with
2-chloro-1,4,7-trienes,7 reacted with alkynes in the presence of MAO at room temperature,
followed by hydrolysis to afford 5–6-fused bicyclic compounds 2 (Eq. 2).9 It is noteworthy that
the reaction gave only exo-trig cyclization products. Moreover, this cyclization renders it
possible to construct a quaternary carbon at the ring junction, where construction is generally
considered to be a difficult task. Some representative examples of the bicycle formation are given
in Table 1.
(2)
Generally, in all instances the addition proceeded at the substituted carbon of the triple bond,
followed by exo-trig cyclization. Initially, the cyclization of chlorodiene was carried out in THF,
which was then removed under reduced pressure and substituted for 1,2-dichloroethane prior to
the addition of MAO and phenyl acetylene. In this case, the bicycle 2a was obtained as a 3:1
mixture of isomers in reasonable yield (61%). However, the change of the solvent during the
course of the reaction was not considered practical and we found that the overall reaction
sequence can be conveniently carried out in toluene. Thus, the reaction of 1 with phenyl-
acetylene (entry 1) in toluene afforded 2a in higher yield (71%) in comparison with the previous
case, also as a 3:1 mixture of isomers. The stereochemistry of the isomers 2a was determined by
comparison with the authentic sample of the cis isomer of 2a which was prepared using a known
procedure.10 The methyl groups at the bridge-head of the cis isomers showed characteristic
chemicals shifts 28.6–29.0 ppm in their 13C NMR spectra. The methyl signals of the trans
isomers appeared at 26.7–26.9 ppm in their 13C NMR spectra.
The use of 4-methoxyphenylacetylene (entry 2) furnished the bicycle 2b in reasonable yield
(65%) as a 1.6:1 mixture of isomers. The reaction with 3-phenylpropyne (entry 3) gave the
bicycle 2c in good yield (72%) as a 1:1 mixture of isomers.
Alkyl substituted acetylenes such as 4-phenylbutyne (entry 4) and 1-octyne (entry 5) reacted
as well and afforded the bicycles 2d and 2e in moderate yields of 56% (3:1 ratio of isomers) and

7907
Table 1
Reaction of 1a with alkynes to give bicycles 2 in the presence of MAO
57% (1:1 ratio of isomers), respectively. Quenching of the reaction mixture with DCl afforded
D-2a in 65% (54%) yield (a 3:1 mixture of diastereoisomers) with deuterium incorporation in
>92% (Eq. 2). Internal alkynes such as 4-octyne did not give the desired product.
The reaction of 1a with phenylacetylene was used to check other methods for the generation
of a cationic species as well. The obtained results can be summarized as follows: (i) the change
of MAO to Me3Al did not result in any reaction, (ii) a combination of Me3Al with a catalytic
amount of B(C6F5)3 (5%) furnished 2a albeit in a low yield of 10%, (iii) the use of AgOSO2CF3
to generate the cationic species did not result in the formation of any observable products, and
(iv) in the presence of a catalytic amount of Ph3CB(C6F5)4 (5 mol%) the reaction proceeded
smoothly to give 2a in good yield (64%).
Surprisingly, the reaction of 1 with methyl- or dimethyl(t-butyl)silylpropargyl ethers afforded
the allene derivative 3 instead of the expected bicyclic compound in 50 and 42% yields,
respectively. The insertion obviously proceeded at the unsubstituted carbon of the triple bond,
giving rise to the a-organozirconium-b-alkoxy compound which underwent dealkoxymetalation
to afford the allene 3 after hydrolysis (Eq. 3). Although the cause of the change in the
regioselectivity of the insertion is not clear, coordination or interaction of the oxygen atom of

7908
the propargyl ethers to the zirconium atom during the course of the reaction is reasonably
presumed. A similar phenomenon has been observed in the reactions of propargylic ether with
organocopper compounds.11
(3)
Interestingly, when compound 4, prepared by the reaction of the Negishi reagent with
9-methoxy-4,5-diethylnona-1,4(Z),7(E)-triene,10 was treated with MAO and phenylacetylene
under the identical conditions, no insertion reaction was observed (Eq. 4). Even after heating the
reaction mixture at 50°C for 24 h, insertion of the triple bond into the ZrꢀC bond did not take
place. After hydrolysis, a mixture of 5 and 6 was formed in 76% (cis:trans=10:1) and 22%
yields, respectively. Inhibition of the insertion of an alkyne may be explained by coordination of
the vinyl group, which blocks the vacant site of the Zr atom of the cationic species. This would
effectively prevent an alkyne from approaching the metalꢀcarbon bond.
(4)
It is reasonable to assume that the mechanism of the reaction of 1a with an alkyne proceeds
as follows: (i) formation of 1a by the reaction of Negishi’s reagent with 2-chloro-4,5-diethyl-
1,4,7-triene, (ii) reaction of 1a with MAO to produce the cationic species 7, (iii) coordination of
an alkyne to the Zr atom giving 8, (iv) insertion of an alkyne into the Zrꢀsp3C bond of 8 to give
9, (v) intramolecular insertion of the exo-methylene moiety into the Zrꢀsp2C bond to afford 10,
and finally hydrolysis furnishes 2 (Scheme 1).
Scheme 1.

7909
References
1. Guram, A. S.; Jordan, R. J. In Comprehensive Organometallic Chemistry II; Abel, E. W.; Stone, F. G. A.;
Wilkinson, G., Eds.; Elsevier: Oxford, 1995; Vol. 4, p. 589.
2. (a) Maeta, H.; Hashimoto, T.; Hasegawa, T.; Suzuki, K. Tetrahedron Lett. 1992, 33, 5965–5968. (b) Maeta, H.;
Suzuki, K. Tetrahedron Lett. 1992, 33, 5969–5973. (c) Maeta, H.; Suzuki, K. Tetrahedron Lett. 1993, 34, 341–344.
(d) Suzuki, K. Pure Appl. Chem. 1994, 66, 1557–1564. (e) Suzuki, K., Hasegawa, T.; Imai, T.; Maeta, H.; Ohba,
S. Tetrahedron 1995, 51, 4483–4494.
3. Christoffers, J.; Bergman, R. G. J. Am. Chem. Soc. 1996, 118, 4715–4716.
4. Shaughnessy, K. H.; Waymouth, R. M. Organometallics 1998, 17, 5728–5745.
5. (a) Yamanoi, S.; Matsumoto, T.; Suzuki, K. Tetrahedron Lett. 1997, 38, 3031–3034. (b) Yamanoi, S.; Imai, S.;
Matsumoto, T.; Suzuki, K. Tetrahedron Lett. 1998, 39, 9727–9731. (c) Yamanoi, S.; Ohrui, H.; Seki, K.;
Matsumoto, T.; Suzuki, K. Tetrahedron Lett. 1999, 40, 8407–8410.
6. Takahashi, T.; Kotora, M.; Kasai, K.; Suzuki, N. Tetrahedron Lett. 1994, 35, 5685–5688.
7. Takahashi, T.; Kotora, M.; Xi, Z.; Suzuki, N. The 69th Annual Meeting of Chemical Society of Japan, Kyoto,
March, 1995, 2H3 43.
8. Millward, D. B.; Waymouth, R. M. Organometallics 1997, 16, 1153–1158.
9. Typical experimental procedure: To a solution of 1a (1 mmol) in toluene, prepared ‘in situ’ from 1 equiv. of
Negishi reagent and 2-chloro-4,5-diethyl-1,4,7-triene (199 mg, 1 mmol), was added 1 mL of toluene solution of
MAO (9 wt%) and phenylacetylene (102 mg, 1 mmol) at −78°C followed by warming to ambient temperature.
After stirring for 3 h, the reaction mixture was quenched with 3N HCl to furnish the corresponding bicyclic
compounds 2. (3aR*,7aR*)-3a,4,7,7a-Tetrahydro-2-phenyl-3a-methyl-5,6-diethylindene (2a). Isolated yield 56%.
1
A 3:1 mixture of isomers. Cis isomer: H NMR (CDCl3, Me4Si) l 0.90 (t, J=7.5 Hz, 6H), 1.12 (s, 3H), 1.19–1.27
(m 10H), 2.92–2.99 (m, 1H), 5.87 (s, 1H), 7.17–7.44 (m, 5H); 13C NMR (CDCl3, Me4Si) l 13.42, 13.47, 25.89,
25.98, 28.61, 34.12, 40.42, 40.44, 43.76, 49.73, 125.48, 126.73, 127.49, 127.92, 128.17, 131.98, 132.96, 135.76,
136.78, 139.17. Trans isomer: 1H NMR (CDCl3, Me4Si) l 0.90 (t, J=7.5 Hz, 6H), 1.12 (s, 3H), 5.73 (s, 1H), other
peaks are covered by the major isomer; 13C NMR (CDCl3, Me4Si) l 13.27, 16.16, 25.76, 26.17, 26.75, 32.65,
37.38, 39.27, 46.34, 49.05, 125.34, 126.51, 126.82, 127.03, 128.25, 130.92, 131.94, 136.50, 138.20, 141.45. HRMS
cacld for C20H26: 266.2034, found: 266.2034.
10. Takahashi, T.; Kotora, M.; Kasai, K. J. Chem. Soc., Chem. Commun. 1994, 2693–2694.
11. Normant, J. F.; Alexakis, A. Synthesis 1981, 841–870.
.
.