Communication pubs.acs.org/Organometallics
Ru(0)-Catalyzed C3-Selective Cross-Dimerization of 2,5-Dihydrofuran with Conjugated Dienes Masafumi Hirano,* Yuki Hiroi, Tasuku Murakami, Hirofumi Ogawa, Sayori Kiyota, Nobuyuki Komine, and Sanshiro Komiya† Department of Applied Chemistry, Graduate School of Engineering, Tokyo University of Agriculture and Technology, 2-24-16 Nakacho, Koganei, Tokyo 184-8588, Japan S Supporting Information *
ABSTRACT: Cross-dimerization of 2,5-dihydrofuran with conjugated dienes enables a straightforward and efficient synthesis of C3-substituted 2,3-dihydrofurans. The reaction has been achieved by Ru(η 6 naphthalene)(η4-1,5-COD) (1) (3−10 mol %) in acetone at room temperature. This protocol is also effective for branched and linear internal conjugated dienes. The stereochemistry of the products suggests that the reaction involves the oxidative coupling step between cisoid-1,3dienes and 2,5-dihydrofuran at a Ru(0) center.
R
elimination, and reductive elimination give the cross-dimer with recovery of the Ru(0) catalyst.10,11 During the course of a study aimed at exploring the Ru(0)-catalyzed cross-dimerizations, we recently found the C3-selective coupling reaction of 2,5dihydrofuran with methyl methacrylate.12 In this paper, we report the C3-selective cross-dimerizations of 2,5-dihydrofuran with a series of conjugated dienes catalyzed by a Ru(0) complex. In initial studies, we explored cross-dimerization of 2,5dihydrofuran (2) with 2,3-dimethylbutadiene (3a) in a 1:1 ratio in benzene catalyzed by Ru(η6-naphthalene)(η4-1,5-COD) (1; 10 mol %) at 50 °C for 6 h (Table 1). The reaction in benzene was not effective and gave a regioisomeric mixture of the crossdimers 4a and 5a, with a cautious total yield (15%) (entry 1). When the amount of 2 was increased, the yield of 4a increased but the yield of the regioisomeric product 5a also increased (entry 3). Under THF or neat conditions, both 4a and 5a were obtained in modest yields (entries 4 and 5). We found the reaction in acetone to give 4a in high yield with inhibition of 5a (entry 6), and 4a was exclusively obtained in 88% yield at 30 °C (entry 7). DMSO and acetylacetone completely stopped the reaction (entries 8 and 9), and the low-polarity solvents seemed to encourage the formation of 5a (entries 10−12). Among the ketones tested, acetone was the best solvent for this reaction (entries 7, 13, and 14). In the reactions including acetone, the major side reaction was isomerization of 2 to 2,3-dihydrofuran, which was found to be inactive to the cross-dimerization by an independent reaction.13 The isomerization mechanism of 2 to 2,3-dihydrofuran is not clear at present. However, because 2 modestly isomerized to 2,3-dihydrofuran in 12% yield under
egioselective introduction of a substituent at the C3 position in monocyclic five-membered heterocycles has attracted longstanding interest, but it is far less common than the C2 substitution reactions.1,2 Dihydrofurans are attractive synthetic targets, since they are subunits of a wide range of biologically active compounds.3−5 However, existing approaches for the C3-substituted 2,3-dihydrofurans are extremely limited. Reliable protocols involve internal cyclization of 4-hydroxybutanal followed by dehydration (Scheme 1a)6 and rearrangements of 2-allenyloxy7 and 2-vinyloxy8 groups in 2,5dihydrofuran (Scheme 1b,c), but their scope is somewhat limited. Scheme 1. Approaches to 3-Substituted 2,3-Dihydrofurans
We have documented cross-dimerizations of conjugated compounds with substituted alkenes catalyzed by Ru(η6naphthalene)(η4-1,5-COD) (1),9 where the naphthalene ligand (6π) is selectively displaced by a conjugated compound (4π) and an alkene (2π) to satisfy the 18e rule, and a subsequent oxidative coupling reaction to form a ruthenacycle, β-hydride © XXXX American Chemical Society
Special Issue: Organometallics in Asia Received: December 2, 2015
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DOI: 10.1021/acs.organomet.5b00987 Organometallics XXXX, XXX, XXX−XXX
Communication
Organometallics Table 1. Solvent Effect on the Reaction of 2,5-Dihydrofuran with 2,3-Dimethylbutadiene by 1a
entry
solvent
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15b
benzene benzene benzene THF neat acetone acetone DMSO acetylacetone CH2Cl2 hexane Et2O 2-butanone cyclohexanone acetone
m for 2 n for 3a 1 1 5 5 5 5 5 5 5 5 5 5 5 5 5
1 5 1 1 1 1 1 1 1 1 1 1 1 1 1
temp (°C)
yield of 4a (%)
yield of 5a (%)
50 50 50 50 50 50 30 30 30 30 30 30 30 30 r.t.
12 20 48 41 51 83 88 0 0 32 36 34 73 12 0
3 7 16 14 8 1 0 0 0 27 35 27 0 0 0
Table 2. Cross-Dimerizations of 2,5-Dihydrofuran with Conjugated Dienesa
a Conditions: 1, 10 mol %; 2, 1−5 mmol; 3a, 1−5 mmol; solvent, 2 mL. Yields were estimated by 1H NMR and GLC using biphenyl as an internal standard. bp-Benzoquinone (10 mol %) was added; reaction time 19 h.
similar conditions without addition of 3a, some hydridoruthenium species generated in the catalytic system may be responsible for this isomerization. The undesired isomerization of 2 to 2,3-dihydrofuran was also found in the ring-closing metathesis of diallyl ether, and 1,4-benzoquinone was reported to suppress the isomerization.14 However, addition of 1,4benzoquinone completely deactivated the present catalyst (entry 15). The optimized conditions are the reaction using 2 and 3a in 5:1 ratio, catalyzed by 10 mol % of 1 in acetone at room temperature for 6 h. The cross-dimer 4a was purified by silica gel column chromatography using hexane/ethyl acetate and was characterized by GC, GC-MS, 1H NMR, COSY, 13C{1H} NMR, and HRMS to be 1-(2,3-dihydrofuranyl)-2,3-dimethyl-2butene. Adopting the above as a standard set of conditions, we investigated the scope of the new C3-selective crossdimerizations of 2,5-dihydrofuran with a series of conjugated dienes (Table 2). With 1,3-butadiene (3b), the reaction proceeded smoothly to give (Z)-4b (entry 2).15 Isoprene (3c) reacted similarly with 2 to give 4c in 81% yield, where a new C−C bond was exclusively formed between the C3position in dihydrofuran and the 4-position in isoprene (entry 3). Treatment of 2 with a terminally substituted diene, (E)-1,3pentadiene (3d), gave a regioisomeric mixture of (Z)-4d (47%) and (Z)-5d (41%) (entry 4). With the more bulky terminally -substituted diene (E)-1-phenyl-1,3-butadiene (3e), however, a regioselective cross-dimerization was achieved to give (E)-4e in 73% yield (entry 5). An internal linear conjugated diene such as 2,4-hexadiene (3f) also afforded the cross-dimers (entry 6). When (1E,3E)-1,4-diphenyl-1,3-butadiene (3g) was employed
a Typical conditions: 1, 10 mol %; 2, 5 mmol; 3, 1 mmol; room temperature; time, 6 h; solvent, acetone (2 mL). Yields were estimated by 1H NMR using biphenyl as an internal standard, except as noted below. All products except 4b were purified by silica gel column chromatography. bConditions: time, 20 h; 2, 2 equiv. cConditions: time, 3 h; mesitylene was used as an internal standard. dConditions: 1, 3 mol %. eConditions: 1, 5 mol %; time, 0.5 h. fTriphenylmethane was used for an internal standard. gIsolated yield. hConditions: 1, 5 mol %; time, 24 h. in.r. = no reaction with respect to diene.
in this reaction, a conjugated diene bearing a tetrahydrofuranyl group (1Z,3E)-6g was dominantly obtained (entry 7). The B
DOI: 10.1021/acs.organomet.5b00987 Organometallics XXXX, XXX, XXX−XXX
Communication
Organometallics trisubstituted conjugated diene 3h also gave the corresponding coupling products (entry 8). It is worth noting that all branched coupling products 4d,g,h are obtained as single diastereomers. The generality of the C3-selective cross-dimerization between 2,5-dihydrofuran and conjugated dienes led us to explore an even more challenging substrate such as a natural terpene.16 Treatment of 2 with β-myrcene 3i gave rise to the C3-selective cross-dimer 4i in 88% yield (entry 9). As described above, this reaction has a wide scope with respect to conjugated dienes, including internal dienes. However, the electron-rich Danishefsky−Kitahara diene17 remained unreacted under these conditions (entry 10), and reaction of 2 with an electrondeficient diene, methyl (2E)-2,4-pentadienoate, gave a complex mixture (entry 11). Cyclic dienes such as 1,3-cyclooctadiene and 1,5-cyclooctadiene remained unreacted, probably owing to their weak coordination ability with Ru(0) (entries 12 and 13).18 The observed reactivity and selectivity are consistent with the catalytic cycle shown in Scheme 2 as a representative reaction of 2 with 3a, which is basically the same mechanism starting from the diene complex19 as described above and elsewhere.9,10
Scheme 3. Possible Formation Mechanism for 5a
In summary, the first example of the C3-selective substitution of 2,5-dihydrofuran with conjugated dienes has been achieved. The reaction proceeds well with a wide range of conjugated dienes. Further investigations into the full scope of this reaction using five-membered heterocycles are ongoing and will be reported in due course.
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ASSOCIATED CONTENT
S Supporting Information *
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.organomet.5b00987. Synthetic procedures and characterization data for the products (PDF)
Scheme 2. Proposed Catalytic Cycle
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AUTHOR INFORMATION
Corresponding Author
*E-mail for M.H.:
[email protected]. Present Address †
Gakushuin University, 1-5-1 Mejiro, Toshima, Tokyo 1710031, Japan. Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS This work was financially supported by Japan Science and Technology Agency (JST) ACT-C. Y.H. acknowledges financial support from a Grant-in-Aid for JSPS Fellows, 25-4284.
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REFERENCES
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There are arguments for the coordination mode of 2 to the transition-metal center. 20,21 Although we failed to get spectroscopic evidence for the intermediates in this catalysis, the most feasible coordination mode is a η2-C,C′-2,5dihydrofuran in the present reaction (intermediate A). Though it is possible to postulate some rotamers of the 2,5dihydrofuran fragment in intermediate A, only a single rotamer must be responsible for the oxidative coupling reaction, because we obtained the single diastereomers in the reactions using 3d,g,h. We also postulated the seven-membered ruthenacycle C from B because the Z isomers of the side-chain group were obtained. Solvent effects on the present cross-dimerization are not clear to date. However, acetone clearly suppresses formation of 5a in the reaction of 2 with 3a (Table 1). A possible formation mechanism for the regioisomer 5e is a pathway through the five-membered ruthenacycle C′ (Scheme 3). Thus, acetone may encourage the π−σ arrangement to give the seven-membered ruthenacycle intermediate C (Scheme 2). C
DOI: 10.1021/acs.organomet.5b00987 Organometallics XXXX, XXX, XXX−XXX
Communication
Organometallics (5) Recently, decarboxylative alkylations, vinylations, and arylations of 2-furylcarboxylic acid have been reported: (a) Chu, L.; Ohta, C.; Zuo, Z.; MacMillan, D. W. C. J. Am. Chem. Soc. 2014, 136, 10886− 10889. (b) Noble, A.; McCarver, S. J.; MacMillan, D. W. C. J. Am. Chem. Soc. 2015, 137, 624−627. (6) Botteghi, C.; Consiglio, G.; Ceccarelli, G.; Stefani, A. J. Org. Chem. 1972, 37, 1835−1837. (7) Dulcère, J.-P.; Crandall, J.; Faure, R.; Santelli, M.; Agati, V.; Mihoubi, M. J. Org. Chem. 1993, 58, 5702−5708. (8) Dulcère, J.-P.; Rodriguez, J. Synthesis 1993, 1993, 399−405. (9) Hirano, M.; Komiya, S. Coord. Chem. Rev. 2015, DOI: 10.1016/ j.ccr.2015.07.008. (10) Hirano, M.; Ueda, T.; Komine, N.; Komiya, S.; Nakamura, S.; Deguchi, H.; Kawauchi, S. J. Organomet. Chem. 2015, 797, 174−184. (11) Although the mechanism is completely different from that of the present reaction, catalytic hydrovinylation of conjugated dienes using ethylene has been reported: (a) RajanBabu, T. V.; Cox, G. A.; Lim, H. J.; Nomura, N.; Sharma, R. K.; Smith, C. R.; Zhang, A. In Comprehensive Organic Synthesis, 2nd ed.; Molander, G. A., Knochel, P., Eds.; Elsevier: Oxford, U.K., 2014; Vol. 5, pp 1582−1620. (b) Timsina, Y. N.; Sharma, R. K.; RajanBabu, T. V. Chem. Sci. 2015, 6, 3994−4008. (12) (a) Hirano, M.; Arai, Y.; Komine, N.; Komiya, S. Organometallics 2010, 29, 5741−5743. (b) Hiroi, Y.; Komine, N.; Komiya, S.; Hirano, M. Org. Lett. 2013, 15, 2486−2489. (13) DFT calculations suggest the HOMO/LUMO energies for 2,5dihydrofuran (−6.26/0.50 eV) and 2,3-dihydrofuran (−5.56/1.15 eV), respectively. One of the reasons for the high reactivity of 2,5dihydrofuran in this reaction is due to the low-lying HOMO and LUMO levels that make a strong interaction with the Ru(0) center in this reaction. See the Supporting Information. (14) Hong, S. H.; Sanders, D. P.; Lee, C. W.; Grubbs, R. H. J. Am. Chem. Soc. 2005, 127, 17160−17161. (15) Slow E/Z isomerization was observed at room temperature. (16) Behr, A.; Johnen, L. ChemSusChem 2009, 2, 1072−1095. (17) Danishefsky, S.; Kitahara, T. J. Am. Chem. Soc. 1974, 96, 7807− 7808. (18) Hirano, M.; Sakate, Y.; Inoue, H.; Arai, Y.; Komine, N.; Komiya, S.; Wang, X.-Q.; Bennett, M. A. J. Organomet. Chem. 2012, 708−709, 46−57. (19) Bennett, M. A.; Wang, X.-Q. J. Organomet. Chem. 1992, 428, C17−C20. (20) Yamamoto, Y.; Kitahara, H.; Ogawa, R.; Itoh, K. J. Org. Chem. 1998, 63, 9610−9611. (21) Elgamiel, R.; Huppert, I.; Lancry, E.; Yerucham, Y.; Schultz, R. H. Organometallics 2000, 19, 2237−2239.
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DOI: 10.1021/acs.organomet.5b00987 Organometallics XXXX, XXX, XXX−XXX
