Organometallics 2009, 28, 669–671
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Ruthenium-Catalyzed Cyclodimerization of Allenynes Nozomi Saito,* Yuki Tanaka, and Yoshihiro Sato* Faculty of Pharmaceutical Sciences, Hokkaido UniVersity, Sapporo 060-0812, Japan ReceiVed December 13, 2008 Summary: The cyclodimerization of R,ω-allenynes using Cp* RuCl(cod) catalyst is described. This reaction proceeds Via an alkylidene ruthenacyclopentene intermediate, which is generated by the oxidatiVe cycloaddition of alkyne and the internal double bond of the allene, to giVe a unique pentacyclic compound haVing two fiVe-membered rings and three four-membered rings in high yields. Since the first report several decades ago of a carbon-carbon bond forming reaction via a ruthenacyclopentene generated by oxidative cycloaddition of alkene and alkyne to a low-valent ruthenium complex,1 many attempts have been made to develop an intermolecular coupling of alkyne and alkene based on the ruthenacyclopentene formation.2 The intramolecular cyclization of enynes via ruthenacyclopentene is also a powerful and promising methodology for the efficient synthesis of cyclic molecules, and several excellent enyne cyclizations have been developed, including skeletal rearrangement,3a-c cycloisomerization,3d,e the Pauson-Khand type reaction,3f,g and [5 + 2] cyclization.3h Recently, we demonstrated enyne cyclizations using a Cp*RuCl(cod) catalyst: alkenylative cyclization under ethylene gas,4a cyclization accompanied by cyclopropane formation,4b and [2 + 2 + 2] cycloaddition of dienyne.4c In contrast to extensive studies of the reactions of alkynes and alkenes, the reaction of alkyne and allene via ruthenacyclopentene remains a frontier in ruthenium catalysis.5 To date, * To whom correspondence should be addressed. E-mail: biyo@ pharm.hokudai.ac.jp. (1) Mitsudo, T.; Kokuryo, K.; Takegami, Y. J. Chem. Soc., Chem. Commun. 1976, 722. (2) For reviews, see: (a) Naota, T.; Takaya, H.; Murahashi, S. Chem. ReV. 1998, 98, 2599. (b) Trost, B. M.; Toste, F. D.; Pinkerton, A. B. Chem. ReV. 2001, 101, 2067. (c) Trost, B. M.; Frederiksen, M. U.; Rudd, M. T. Angew. Chem., Int. Ed. 2005, 44, 6630. (d) Ruthenium in Organic Synthesis; Murahashi, S., Ed.; Wiley-VCH: New York, 2002. (e) Ruthenium Catalysts and Fine Chemistry; Bruneau, C., Dixneuf, P. H., Eds.; Springer-Verlag: Berlin, Heidelberg, 2004; Top. Organomet. Chem. Vol. 11. (3) For representative examples, see: (a) Chatani, N.; Morimoto, T.; Muto, T.; Murai, S. J. Am. Chem. Soc. 1994, 116, 6049. (b) Trost, B. M.; Doherty, G. A. J. Am. Chem. Soc. 2000, 122, 3801 For similar reactions catalyzed by Ru-NHC catalysts, see: (c) Ackermann, L.; Bruneau, C.; Dixneuf, P. H. Synlett 2001, 397. (d) Trost, B. M.; Toste, F. D. J. Am. Chem. Soc. 1999, 121, 9728. (e) Trost, B. M.; Toste, F. D. J. Am. Chem. Soc. 2000, 122, 714. (f) Morimoto, T.; Chatani, N.; Fukumoto, Y.; Murai, S. J. Org. Chem. 1997, 62, 3762. (g) Kondo, T.; Suzuki, N.; Okada, T.; Mitsudo, T. J. Am. Chem. Soc. 1997, 119, 6187. (h) Trost, B. M.; Toste, F. D.; Shen, H. J. Am. Chem. Soc. 2000, 122, 2379. (4) (a) Mori, M.; Saito, N.; Tanaka, D.; Takimoto, M.; Sato, Y. J. Am. Chem. Soc. 2003, 125, 5606. (b) Tanaka, D.; Sato, Y.; Mori, M. Organometallics 2006, 25, 799. (c) Tanaka, D.; Sato, Y.; Mori, M. J. Am. Chem. Soc. 2007, 129, 7730. (5) (a) Oh, C. H.; Gupta, A. K.; Park, D. I.; Kim, N. Chem. Commun. 2005, 5670. (b) Bai, T.; Xue, P.; Zhang, Li.; Ma, S.; Jia, G. Chem. Commun. 2008, 2929. For Ru-catalyzed intermolecular reactions of allene and other multiple bonds, see: (c) Yamaguchi, M.; Kido, Y.; Omata, K.; Hirama, M. Synlett 1995, 1181. (d) Trost, B. M.; Pinkerton, A. B. J. Am. Chem. Soc. 1999, 121, 4068. For Ru-catalyzed intramolecular reactions of allenynes, see: (e) Vovard-Le Bray, C.; De´rien, S.; Dixneuf, P. H.; Murakami, M. Synlett 2008, 193.
Scheme 1. Two Possible Ruthenacyclopentenes from Allenyne
Scheme 2. Ruthenium-Catalyzed Cyclization of Allenyne 1a
only intramolecular [2 + 2] cycloaddition5a and intermolecular coupling using cyclonona-1,2-diene have been reported.5b Both reactions proceed via the ruthenacyclopentene I, in which the terminal carbon of allene is attached to the ruthenium metal (Scheme 1). There have been no examples of the formation of a type II ruthenacycle, in which the center carbon of allene is attached to the ruthenium metal center.6 Here, we report a unique ruthenium-catalyzed cyclodimerization of R,ω-allenynes, providing the first example of cyclization via the type II ruthenacyclopentene intermediate. First, allenyne 1a was reacted under ethylene gas (1 atm) in the presence of Cp*RuCl(cod) (5 mol %) in toluene under reflux conditions according to our previously reported procedure for the alkenylative cyclization of enynes,4a affording a trace amount of the cyclic compound 2 with a triene part (Scheme 2). This result indicated that the reaction proceeded via the formation of ruthenacycle 3a and insertion of ethylene, followed by β-elimination from 4. Encouraged by this result, to improve the yield of the cyclized product, we investigated the effect of substituents on allene and alkyne (Table 1). In the reaction of allenyne 1b, which has a (6) For representative examples of cyclization via type I or II metallacycles formed from allenynes and transition metals except for ruthenium, see: (a) Negishi, E.; Holmes, S. J.; Tour, J. M.; Miller, J. A.; Cederbaum, F. E.; Swanson, D. R.; Takahashi, T. J. Am. Chem. Soc. 1989, 111, 3336. (b) Aubert, C.; Llerena, D.; Malacria, M. Tetrahedron Lett. 1994, 35, 2341. (c) Llerena, D.; Aubert, C.; Malacria, M. Tetrahedron Lett. 1996, 37, 7027. (d) Urabe, H.; Takeda, T.; Hideura, D.; Sato, F. J. Am. Chem. Soc. 1997, 119, 11295. (e) Ahmar, M.; Locatelli, C.; Colombier, D.; Cazes, B. Tetrahedron Lett. 1997, 38, 5281. (f) Brummond, K. M.; Wan, H. Tetrahedron Lett. 1998, 39, 931. (g) Pagenkopf, B. L.; Belanger, D. B.; O’Mahony, D. J. R.; Livinghouse, T. Synthesis 2000, 1009. (h) Kobayashi, T.; Koga, Y.; Narasaka, K. J. Organomet. Chem. 2001, 624, 73. (i) Brummond, K. M.; Chen, H.; Sill, P.; You, L. J. Am. Chem. Soc. 2002, 124, 15186. (j) Shen, Q.; Hammond, G. B. J. Am. Chem. Soc. 2002, 124, 6534. (k) Brummond, K. M.; Mitasev, B. Org. Lett. 2004, 6, 2245. (l) Mukai, C.; Inagaki, F.; Yoshida, T.; Yoshitani, K.; Hara, Y.; Kitagaki, S. J. Org. Chem. 2005, 70, 7159. (m) Jiang, X.; Ma, S. J. Am. Chem. Soc. 2007, 129, 11600.
10.1021/om801181a CCC: $40.75 2009 American Chemical Society Publication on Web 01/05/2009
670 Organometallics, Vol. 28, No. 3, 2009
Communications Table 2. Cyclodimerization of Various Allenynesa
Table 1. Effect of Substituent on Multiple Bonds
run
substrate
conditionsa
yield (%)
1 2 3 4b 5
1b (R ) Me, R ) H) 1c (R1 ) H, R2 ) tBu) 1d (R1 ) Me, R2 ) tBu) 1d 1d
reflux, 2.5 h 50 °C, 28 h room temp, 6 h room temp, 20 h 50 °C, 1 h
13 (5b) 32 (5c) 93 (5d)
1
2
95 (5d)
a
Other conditions: atmosphere (1 atm): ethylene (runs 1-3), argon (runs 4 and 5). b Allenyne 1d was recovered in 90% yield.
methyl group on the alkyne, the unexpected compound 5b was obtained in 13% yield as a single isomer under the aforementioned conditions (run 1) instead of the desired alkenylative cyclization product. High-resolution mass spectroscopy of the compound indicated that the compound was a dimer of 1b. The reaction of allenyne 1c, which has a tert-butyl group on the allene part, also gave only the corresponding dimer 5c in 32% yield (run 2). Surprisingly, the dimerization of allenyne 1d, which has substituents on both the allene and alkyne moieties, proceeded smoothly at room temperature to afford the dimer 5d in 93% yield (run 3). Detailed analyses of various spectral data, including 2D-NMR (COSY, NOESY, HMQC, and HMBC), allowed us to characterize the dimer structures of 5b-d as having a unique pentacyclic core, including two five-membered rings and three four-membered rings.7 Ethylene molecules were not incorporated into the dimers in this reaction. Therefore, we performed the reaction of 1d with Cp*RuCl(cod) under argon atmosphere (1 atm; runs 4 and 5). Although the cyclodimerization of 1d did not proceed at room temperature under an argon atmosphere (run 4), the reaction at 50 °C gave 5d in 95% yield in the absence of ethylene (run 5). These results suggested that the presence of ethylene facilitates ligand dissociation from the ruthenium catalyst and formation of the active species. The scope of the ruthenium-catalyzed cyclodimerization under the same conditions is summarized in Table 2. Allenynes 1e,f also afforded the pentacyclic compounds 5e,f, respectively, in excellent yields (runs 1 and 2). The reactions of 1g-i, which have an aromatic group on the alkyne part, gave 5g-i in good to high yields (runs 3-5). Dimerization of 1j with a siloxylmethyl group on the alkyne moiety provided 5j in 91% yield (run 6). The reaction of allenynes with a cyclic acetal part, 1k,l, also afforded 5k,l, respectively, in high yields (runs 7 and 8). It is noteworthy that 1m,l, containing a heteroatom in the chain, were also applicable to the cyclodimerization, giving the heterocycles 5m,n, respectively (runs 9 and 10). A possible reaction course of the cyclodimerization is shown in Scheme 3. Dissociation of cod from Cp*RuCl(cod) occurs initially to give the Cp*RuCl complex. Allenyne 1 coordinates to the ruthenium center to give the intermediate 6, in which the R2 group on the allene is oriented to avoid steric repulsion by (7) The structures of all dimeric products were strongly supported by both high-resolution mass spectroscopy and various 2D NMR spectroscopic methods (COSY, NOESY, HMQC, and HMBC). The stereochemistries of the products were assigned by analogy with the spectral data of 5g, whose stereochemistry was unambiguously determined by X-ray crystallographic analysis. Crystallographic data for 5g have been deposited at the Cambridge Crystallographic Data Center (CCDC).
a Reaction conditions: Cp*RuCl(cod) (5 mol %), toluene, 50 °C, under Ar (1 atm).
Scheme 3. Possible Reaction Course
the bulky Cp* ligand. Next, oxidative cycloaddition of the alkyne and the internal double bond of the allene afforded the alkylidene ruthenacyclopentene 7, from which the reductive elimination proceeds to give the cyclobutene intermediate 8.8 Again, oxidative cycloaddition of two molecules of 8 to Cp*RuCl occurs to afford the ruthenacycle intermediate 10 and reductive elimination from 10 gives the dimer 5 along with the regeneration of Cp*RuCl.9 (8) For examples of cyclobutene synthesis by ruthenium-catalyzed [2 + 2] cycloaddition, see: (a) Mitsudo, T.; Kokuryo, K.; Shinsugi, T.; Nakagawa, Y.; Watanabe, Y.; Takegami, Y. J. Org. Chem. 1979, 44, 4492. (b) Mitsudo, T.; Naruse, H.; Kondo, T.; Ozaki, Y.; Watanabe, Y. Angew. Chem., Int. Ed. Engl. 1994, 33, 580. (c) Yi, C. S.; Lee, D. W.; Chen, Y. Organometallics 1999, 18, 2043. (d) Yamamoto, Y.; Kitahara, H.; Ogawa, R.; Kawaguchi, H.; Tatsumi, K.; Itoh, K. J. Am. Chem. Soc. 2000, 122, 4310. (e) Jordan, R. W.; Tam, W. Org. Lett. 2000, 2, 3031. (f) Le Paih, J.; De´rien, S.; Bruneau, C.; Demerseman, B.; Toupet, L.; Dixneuf, P. H. Angew. Chem., Int. Ed. 2001, 40, 2912. (g) Alvarez, P.; Gimeno, J.; Lastra, E.; Garcı´a-Granda, S.; Van der Maelen, J. F.; Bassetti, M. Organometallics 2001, 20, 3762. (h) Tenaglia, A.; Giordano, L. Synlett 2003, 2333. (i) Le Paih, J.; De´rien, S.; Demerseman, B.; Bruneau, C.; Dixneuf, P. H.; Toupet, L.; Dazinger, G.; Kirchner, K. Chem. Eur. J. 2005, 11, 1312. See also ref 1.
Communications Scheme 4. Crossover Experiment
To gain further insight into the above reaction course, we conducted a crossover experiment using allenynes 1d,e (Scheme 4). The reaction of a 1d,e mixture (1:1 ratio) with Cp*RuCl(cod) afforded the heterodimer 11 in 46% yield along with homodimers 5d,e, respectively, in 23% yields. This result is consistent with our speculation that the allenyne dimerization proceeded entirely in an intermolecular fashion. (9) For construction of polycyclobutane frameworks via rutheniumcatalyzed [2 + 2] cycloaddition of cyclobutene and DMAD, see: Warrener, R. N.; Abbenante, G.; Kennard, C. H. L. J. Am. Chem. Soc. 1994, 116, 3645. For other examples of ruthenium-catalyzed dimerization of strained alkenes, see: Mitsudo, T.; Suzuki, T.; Zhang, S.-W.; Imai, D.; Fujita, K.; Manabe, T.; Shiotsuki, M.; Watanabe, Y.; Wada, K.; Kondo, T. J. Am. Chem. Soc. 1999, 121, 1839.
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In summary, we have developed a novel ruthenium-catalyzed cyclodimerization of allenynes, giving unique pentacyclic compounds in good to excellent yields. This is the first example of a reaction via a type II ruthenacyclopentene generated by oxidative cycloaddition of alkyne and an internal double bond of allene to the ruthenium complex. This result provides a new protocol for the construction of polycyclic compounds in organic synthesis and new insights into the chemistry of ruthenium catalysis.
Acknowledgment. Part of this work was supported by a Grant-in-Aid for Science Research on Priority Areas (No. 19027005, Synergy of Elements) from the MEXT, Japan, a Grant-in-Aid for Young Scientist (B) (No. 19790002), and a Grant-in-Aid for Scientific Research (B) (No. 19390001) from the JSPS. Supporting Information Available: Text and figures giving details of the synthesis of allenynes, experimental procedures, and spectral data. This material is available free of charge via the Internet at http://pubs.acs.org. OM801181A
