48
Organometallics 2009, 28, 48–50
Ruthenium-Catalyzed Oxypropargylation of Alkenes Yoshihiro Yamauchi, Yoshihiro Miyake, and Yoshiaki Nishibayashi* Institute of Engineering InnoVation, School of Engineering, The UniVersity of Tokyo, Yayoi, Bunkyo-ku, Tokyo 113-8656, Japan ReceiVed NoVember 17, 2008 Summary: The ruthenium-catalyzed oxypropargylation of alkenes with propargylic alcohols and simple alcohols has been found Via ruthenium-allenylidene complexes as key intermediates. As a synthetic application, an intramolecular cyclization using this method has been deVeloped to giVe the corresponding anti-1-alkoxy-3-ethynylindanes in high to excellent yields with a high diastereoselectiVity. Functionalization of alkenes is one of the most attractive subjects in organic synthesis. A variety of reactions such as epoxidation, dihydroxylation, aminohydroxylation, hydroboration, hydrosilylation, cyclopropanation, and carbonylation, including their asymmetric versions, have been known for the introduction of new functional groups into alkene substrates.1 We have recently disclosed the ruthenium-catalyzed carboncarbon bond forming process between propargylic alcohols and alkenes which proceeded via an allenylidene2-ene type process (Scheme 1, path a).3 Here, if the selective capture of in situ produced reactive carbocation intermediates by other nucleophiles is possible, this may lead to a new method for heterofunctionalization of alkenes (Scheme 1, path b). In fact, we have now found that the ruthenium-catalyzed oxypropargylation of alkenes with propargylic alcohols and simple alcohols gave the corresponding functionalized compounds in high to excellent yields with a complete selectivity. Preliminary results are described here. Treatment of 1-phenyl-2-propyn-1-ol (1a) with 5 equiv of ethyl vinyl ether (2a) in the presence of 2.5 mol % of [Cp*RuCl(µ2-SMe)]24 (Cp* ) η5-C5Me5; 3a) in ethanol at 0 °C for 12 h gave 5,5-diethoxy-3-phenyl-1-pentyne (4a) in 93% isolated yield (Scheme 2). Use of a complex bearing a sterically more demanding moiety, [Cp*RuCl(µ2-SiPr)]24 (3b), had no effect on the yield of 4a. The reaction with 3 equiv of 2a proceeded smoothly, 4a being obtained in 91% isolated yield together with a small amount of propargylic ether (5a). Separately, we confirmed that no reaction occurred at all when * To whom correspondence should be addressed. E-mail: ynishiba@ sogo.t.u-tokyo.ac.jp. (1) For a review, see: Catalytic Heterofunctionalization; Togni, A., Gru¨tzmacher, H., Eds.; Wiley-VCH: Weinheim, Germany, 2001. (2) For recent reviews, see: (a) Bruneau, C.; Dixneuf, P. H. Angew. Chem., Int. Ed. 2006, 45, 2176. (b) Metal Vinylidenes and Allenylidenes in Catalysis; Bruneau, C., Dixneuf, P. H., Eds.; Wiley-VCH: Weinheim, Germany, 2008. (3) (a) Nishibayashi, Y.; Inada, Y.; Hidai, M.; Uemura, S. J. Am. Chem. Soc. 2003, 125, 6060. (b) Nishibayashi, Y.; Yoshikawa, M.; Inada, Y.; Hidai, M.; Uemura, S. J. Am. Chem. Soc. 2004, 126, 16066. (c) Daini, M.; Yoshikawa, M.; Inada, Y.; Uemura, S.; Sakata, K.; Kanao, K.; Miyake, Y.; Nishibayashi, Y. Organometallics 2008, 27, 2046. (d) Fukamizu, K.; Miyake, Y.; Nishibayashi, Y. J. Am. Chem. Soc. 2008, 130, 10498. (4) For the preparation of a variety of chalcogenolate-bridged diruthenium complexes, including X-ray analysis and their catalytic activity toward the propargylic substitution reactions, see: (a) Nishibayashi, Y.; Imajima, H.; Onodera, G.; Hidai, M.; Uemura, S. Organometallics 2004, 23, 26. (b) Nishibayashi, Y.; Imajima, H.; Onodera, G.; Inada, Y.; Hidai, M.; Uemura, S. Organometallics 2004, 23, 5100.
Scheme 1
Scheme 2
other catalysts such as the monoruthenium complex [CpRuCl(PPh3)2] and p-toluenesulfonic acid were used in place of 3. In addition, no reaction took place at all when propargylic alcohols bearing an internal alkyne moiety were used as substrates. Typical results of reactions of other propargylic alcohols with 2a under the same reaction conditions are shown in Table 1. The presence of a substituent such as a fluoro, chloro, methoxy, or methyl group at the para position of the benzene ring of 1 did not have much effect on the yield of 4 (Table 1, runs 1-5). Reactions of propargylic alcohols bearing a methyl group at the meta and ortho positions of the benzene ring of 1 with 2a proceeded smoothly to give the corresponding oxypropargylated products in excellent yields (Table 1, runs 6 and 7). Use of a 2-furyl, 1-naphthyl, or vinylic group in place of the phenyl group gave a similar yield of 4 (Table 1, runs 8-10). Separately, we confirmed that compounds 4 were readily transformed into the corresponding 4-pentynals in quantitative yields.5 On the other hand, the reaction of 1-cyclohexyl-2-propyn-1-ol with 2a afforded only the corresponding propargylic ether (5b) in 99% yield. In addition to ethanol, other alcohols such as nPrOH and i PrOH are revealed to be available as nucleophiles (Table 1, runs 11 and 12). The reaction with n-butyl vinyl ether (2b) gave the corresponding product in 92% yield as a mixture of two diastereoisomers (Table 1, run 13). Reactions of 1a with substituted vinylic ethers such as 1-ethoxy-1-propene (2c), (5) See the Supporting Information for experimental details.
10.1021/om801092a CCC: $40.75 2009 American Chemical Society Publication on Web 11/26/2008
Communications
Organometallics, Vol. 28, No. 1, 2009 49
Table 1. Ruthenium-Catalyzed Oxypropargylation of Vinyl Ethers (2)a
run
R1 (1)
R2 (2)
R3OH
1 2 3 4 5 6 7 8 9 10 11 12 13
Ph (1a) p-FC6H4 (1b) p-C1C6H4 (1c) p-MeOC6H4 (1d) p-MeC6H4 (1e) m-MeC6H4 (1f) o-MeC6H4 (1g) 2-furyl (1h) 1-naphthyl (1i) Ph2CdCH (1j) Ph (1a) Ph (1a) Ph (1a)
Et (2a) Et (2a) Et (2a) Et (2a) Et (2a) Et (2a) Et (2a) Et (2a) Et (2a) Et (2a) Et (2a) Et (2a) n Bu (2b)
EtOH EtOH EtOH EtOH EtOH EtOH EtOH EtOH EtOH EtOH n PrOH i PrOH EtOH
Scheme 5
yield ratio of of 4 (%)b diastereoisomers 93 (4a) 88 (4b) 93 (4c) 92 (4d) 94 (4e) 98 (4f) 98 (4g) 86 (4h) 97 (4i) 95 (4j) 95 (4k) 90 (4l) 92 (4m)
Scheme 6 50:50 53:47 50:50
a All reactions of 1 (0.20 mmol) with 2 (1.00 mmol) were carried out in the presence of 3a (0.005 mmol) at 0 °C for 12 h in R3OH (2 mL). b Isolated yield.
Scheme 3 Scheme 7
Scheme 4
1-ethoxy-2-methyl-1-propene (2d), and 3,4-dihydro-2H-pyran (2e) proceeded smoothly to give the corresponding products (4n-p6) in excellent yields (Scheme 3). Interestingly, 4p was easily converted into the corresponding 1,4-enyne (4p′) in 42% yield. On the other hand, no oxypropargylation occurred when other alkenes such as styrene were used in place of 2. In order to obtain some information on the reaction pathway, the following stoichiometric and catalytic reactions were investigated. Treatment of the allenylidene complex 6,7 which was separately prepared from the reaction of 3a with 1a, with excess amounts of 2a and 1e in ethanol gave 4a in 53% yield together with 4e in 99% yield (Scheme 4). On the other hand, the reaction of 1a with 2a in the presence of 5 mol % of 6 proceeded smoothly to give 4a in 89% yield. These results indicate that allenylidene complexes are surely key intermediates for this oxypropargylation. On the basis of these findings, a proposed reaction pathway is shown in Scheme 5. At present, we consider that the attack of a vinyl ether on the electron-deficient γ-carbon of I occurs (6) The molecular structure of a diastereoisomer of 4p was confirmed by X-ray analysis. See the Supporting Information for experimental details. (7) Nishibayashi, Y.; Milton, M. D.; Inada, Y.; Yoshikawa, M.; Wakiji, I.; Hidai, M.; Uemura, S. Chem. Eur. J. 2005, 11, 1433.
to give the corresponding alkynyl complex II, followed by the attack of an alcohol on the cationic -carbon of II to afford the corresponding oxypropargylated product via the rutheniumvinylidene complex III. As described in our previous reports,8 we believe that the synergistic effect9 in the diruthenium complexes is quite important for the promotion of this catalytic reaction. Next, we investigated the intramolecular version of this oxypropargylation. The reaction of a propargylic alcohol bearing an alkene moiety (7) in the presence of 3 mol % of 3a in ethanol at 0 °C for 2 h gave 1-ethoxy-3-ethynyl-1-phenylindane (8a) in 87% isolated (97% GLC) yield as a mixture of two diastereoisomers, the anti isomer being the major species (anti8a:syn-8a ) 92:8) (Scheme 6). The molecular structure of the major isomer (anti-8a) was confirmed by X-ray analysis.5 The complex 3b could be similarly employed, 8a being obtained in 85% isolated yield with a similar diastereoselectivity. Intramolcular cyclization of 7 was carried out in a variety of alcohols in place of ethanol. Typical results are shown in Table 2. In all cases, the corresponding 1-alkoxy-3-ethynylindanes (8) were obtained in high to excellent yields with a high diastereoselectivity (Table 2, runs 2-5). This intramolecular cyclization seems to proceed mainly through such a transition state as shown in Scheme 7. The attack of an alcohol on the reactive intermediate from the opposite (8) For recent examples, see: (a) Yamauchi, Y.; Onodera, G.; Sakata, K.; Yuki, M.; Miyake, Y.; Uemura, S.; Nishibayashi, Y. J. Am. Chem. Soc. 2007, 129, 5175. (b) Matsuzawa, H.; Miyake, Y.; Nishibayashi, Y. Angew. Chem., Int. Ed. 2007, 46, 6488. (c) Yamauchi, Y.; Yuki, M.; Tanabe, Y.; Miyake, Y.; Inada, Y.; Uemura, S.; Nishibayashi, Y. J. Am. Chem. Soc. 2008, 130, 2908. (9) Ammal, S. C.; Yoshikai, N.; Inada, Y.; Nishibayashi, Y.; Nakamura, E. J. Am. Chem. Soc. 2005, 127, 9428.
50
Organometallics, Vol. 28, No. 1, 2009
Communications
Table 2. Ruthenium-Catalyzed Intramolecular Oxypropargylation (7)a
run
ROH
time (h)
yield of 8 (%)b
anti-8:syn-8c
1 2 3 4 5
EtOH MeOH n PrOH i PrOH n BuOH
2 2 3 3 3
87 (8a) 81 (8b) 91 (8c) 78 (8d) 95 (8e)
92:8 96:4 96:4 95:5 92:8
a All reactions of 7 (0.20 mmol) in ROH (2.5 mL) were carried out in the presence of 3a (0.006 mmol) at 0 °C. b Isolated yield. c Determined by 1H NMR.
site of the ruthenium-alkynyl moiety may lead to the formation of anti-8. Namely, the steric bulkiness of the ruthenium-alkynyl moiety may inhibit the formation of syn-8. In summary, we have found the ruthenium-catalyzed oxypropargylation of alkenes with propargylic alcohols and simple alcohols via ruthenium-allenylidene complexes as key inter-
mediates. As a synthetic application, an intramolecular cyclization has been developed to give the corresponding anti-1-alkoxy3-ethynylindanes in high to excellent yields with a high diastereoselectivity. The methodology described in this paper provides a novel synthetic approach to heterofunctionalization of alkenes. Further work is currently in progress to broaden its synthetic applicability to natural products and pharmaceuticals.
Acknowledgment. This work was supported by Grantsin-Aid for Scientific Research for Young Scientists (S) (No. 19675002) and for Scientific Research on Priority Areas (No. 18066003) from the Ministry of Education, Culture, Sports, Science and Technology of Japan. Y.N. thanks the Mazda Science and Technology Foundation and the Iwatani Naoji Foundation. Supporting Information Available: Text, figures, tables, and CIF files giving experimental procedures, spectroscopic data, and X-ray data. This material is available free of charge via the Internet at http://pubs.acs.org. OM801092A
