DOI: 10.1002/chem.201402218
Communication
& Synthetic Methods
Synthesis of Cyclobutenes and Allenes by Cobalt-Catalyzed Cross-Dimerization of Simple Alkenes with 1,3-Enynes Akira Nishimura,[a] Eri Tamai,[a] Masato Ohashi,[a] and Sensuke Ogoshi*[a, b] Abstract: Cobalt-catalyzed cross-dimerization of simple alkenes with 1,3-enynes is reported. A [2 + 2] cycloaddition reaction occurred, with alkenes bearing no allylic hydrogen, by reductive elimination of a h3-butadienyl cobaltacycle. On the other hand, aliphatic alkenes underwent 1,4hydroallylation by means of exo-cyclic b-H elimination. These reactions can provide cyclobutenes and allenes that were previously difficult to access, from simple substrates in a highly chemo- and regioselective manner.
Scheme 1. Cobalt-catalyzed cross-dimerization of alkenes with alkynes.
strained cyclopentene has an interim reactivity between simple alkenes and norbornenes, affording both cyclobutene and 1,4-diene.[8] However, the chemoselectivity mainly depends on the structural nature of the alkenes. Therefore, it is a challenge to develop a transformation that can provide previously inaccessible products beyond conventional reactivity. Herein, we report the cobalt-catalyzed cross-dimerization of simple alkenes with 1,3-enynes to afford cyclobutenes or tetrasubstituted allenes. 1,3-enynes display totally different chemoselectivity compared to that of internal alkynes. We have previously developed a nickel-catalyzed [2 + 2] cycloaddition of alkenes with 1,3-enynes (Scheme 2).[9] On the
Oxidative cyclization of two p components at a transitionmetal center to form a metallacycle is a fundamental reaction in the field of organometallic chemistry. This process is accepted as the key step for a variety of synthetic methods, such as cycloaddition, linear oligomerization, reductive coupling, and multicomponent reactions.[1–3] Catalytic variants of these transformations are frequently achieved with late transition metals, of which cobalt is attractive because it can efficiently catalyze the dimerization of electronically unbiased unsaturated hydrocarbons.[4, 5] The groups of Hilt and Cheng have demonstrated the cross-dimerization of simple alkenes with internal alkynes, in the presence of a cobalt(I)/1,3-bis(diphenylphosphino)propane (dppp) catalyst, to furnish linear dienes (Scheme 1).[6] These cross-dimerization reactions are proposed to proceed via a cobaltacyclopentene intermediate, which undergoes b-H elimination, followed by reductive elimination. The difference in chemoselectivity between the formation of 1,3-dienes by means of endo-cyclic b-H elimination and 1,4-dienes, by means of exo-cyclic b-H elimination occurs in the absence and in the presence of allylic hydrogen atoms on the alkene substrates. On the other hand, [2 + 2] cycloaddition occurs in the reaction of highly strained bicyclic alkenes, such as norbornene, with alkynes by means of direct reductive elimination from the corresponding cobaltacycle.[7] Hilt et al. also reported that less-
Scheme 2. Nickel-catalyzed [2 + 2] cycloaddition of electron-deficient alkenes with 1,3-enynes. EWG = electron-withdrawing group
basis of a stoichiometric study, the key step of this [2 + 2] cycloaddition was the formation of an h3-butadienyl nickelacycle, which might prevent undesired pathways, such as b-H elimination and the insertion of another p substrate. On comparison with electron-deficient alkenes, unactivated simple alkenes are less reactive in the nickel-catalyzed reaction, and the resultant product was a mixture of isomers. Thus, we next focused on the cobalt catalyst, which has both good reactivity and selectivity in the cross-dimerization of unactivated alkenes with alkynes. We assumed that, as with nickel catalysis, if the oxidative cyclization of alkenes with 1,3-enynes at the cobalt center can occur to form a h3-butadienyl intermediate, then b-H elimination could be avoided, and cyclobutenes could be provided by means of reductive elimination. In fact, two examples can
[a] A. Nishimura, E. Tamai, Dr. M. Ohashi, Prof. Dr. S. Ogoshi Department of Applied Chemistry Faculty of Engineering, Osaka University Suita, Osaka 565-0871 (Japan) Fax: (+ 81) 6-6879-7394 E-mail: [email protected] [b] Prof. Dr. S. Ogoshi JST, Advanced Catalytic Transformation Program for Carbon Utilization (ACT-C) Suita, Osaka 565-0871 (Japan) Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201402218. Chem. Eur. J. 2014, 20, 1 – 6
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Communication be found in the literature, showing that 1,3-enynes facilitate [2 + 2] cycloaddition with alkenes under cobalt catalysis.[7a, 8] To elucidate our working hypothesis, we first examined the reactions of two different types of alkenes with a 1,3-enyne. Based on the reaction conditions developed by the groups of Hilt and Cheng,[6] a CoBr2/dppp/Zn/ZnI2 (ratio 1:1:4:4) catalyst system was used. As expected, styrene (1) reacted with 2methyl-1-hexen-3-yne (2) in the presence of the cobalt catalyst to give desired cyclobutene 3 in 80 % yield [Eq. (1)].
CC reductive elimination. Then, C undergoes reductive elimination to give allene 5. According to the preliminary results and mechanistic hypothesis, alkenes with no allylic hydrogen atoms have the potential to undergo [2 + 2] cycloaddition with 1,3-enynes. Several optimizations of reaction conditions were investigated based on Equation (1) (for details, see the Supporting Information).[13] An equimolar, or a slightly excessive, amount of 1 was enough to obtain 3 in a sufficient yield. A screening of ligands revealed that only dppp was suitable for catalytic conversion into the product. The reaction with dppe, rac-BINAP, or BIHEP gave cyclobutene 3 in approximately 10 % yield.[14] The use of other mono- or bidentate ligands was unsuccessful. Regarding cobalt(II) salts, CoBr2, CoI2, and Co(OAc)2 were applicable to this [2 + 2] cycloaddition, whereas CoCl2 was less effective. After further optimizations, we selected the reaction conditions as follows: CoBr2/dppp/Zn/ZnI2 (1:1:1:2) as the catalyst, 2 mol % catalyst loading, and CH2Cl2 as the solvent. Next, the [2 + 2] cycloaddition of styrene derivatives with enyne 2 was examined (Scheme 4). Under the optimized conditions, cyclobutene 3 was obtained in 79 % isolated yield. The reaction of para-methylstyrene and para-methoxystyrene gave 6 and 7 in 83 and 80 % yield, respectively. Halogen atoms (F, Cl, and Br) at the para-position were compatible with this [2 + 2] cycloaddition, and provided the corresponding cyclobutenes 8–10 in high yields. These halogen substituents, Br and Cl substituents in particular, can be further functionalized by crosscoupling reactions. Among the meta-substituted styrenes employed, the reaction of meta-methylstyrene was comparable to the corresponding para-substituted example, giving 11 in 83 % yield. On the other hand, electron-withdrawing groups, such as CF3 and F groups, decreased the reactivity to afford 12 and 13 in 23 and 43 % yields, respectively. ortho-Tolyl-substituted 14 was obtained in only 8 % yield, probably owing to steric hindrance. However, neither ortho-methoxy- nor ortho-chlorosubstituents diminished the reactivity and provided compounds 15 (91 %) and 16 (51 %), respectively. In these cases, the reactions might be facilitated by chelation to the cobalt center through an oxygen- or chlorine atom. para-Cyanostyrene and 2-vinylpyridne did not react at all, probably owing to the deactivation of the catalyst by the strong coordination of the nitrogen atom. Although the yields were more modest, vinylboronate and vinylsilane reacted to provide cyclobutenes 17 and 18, which can be utilized for further transformations, such as cross-coupling, allylic substitution, and oxidation. The scope of 1,3-enynes was also investigated. The reaction of enynes bearing longer alkyl chains, and chloro- or silyloxy substituents afforded the corresponding cyclobutenes 19, 20, and 21 in moderate to high yields. With 5 mol % catalyst loading, 1,5-dien-3-yne also reacted to give 1,2-diisopropenylcyclobutene 22 in 49 % yield. 1,3-Enynes bearing a naked vinyl group were also applied to this reaction, affording 23 (50 %) and 24 (34 %) in the presence of 5 mol % catalyst loading. However, a competing homodimerization of enynes was also observed.[15] Although the yield of the product was not improved, the slow addition of the enyne through a syringe drive suppressed the formation of the enyne dimer in the case of 23. As
In contrast to the nickel-catalyzed reaction, the cobalt-catalyzed [2 + 2] cycloaddition proceeded even at room temperature and 3 was obtained as a single regioisomer. On the other hand, the reaction of 1-decene (4) with 2 gave no cyclobutene under the same conditions; instead, tetrasubstituted allene 5 was obtained as the major product in 76 % yield, accompanied by a small amount of unidentified isomers [Eq. (2)].[10] Although the cobalt-catalyzed cross-dimerization of alkenes with alkynes gives (E,E)-dienes,[6] the configuration of the alkenyl moiety of 5 was Z. The difference in the reactivity of alkenes 1 and 4, under cobalt catalysis, can be rationalized as described in Scheme 3. In both cases, the reaction is initiated by the oxidative cyclization of an alkene with a 1,3-enyne at the cobalt(I) center, forming a h3-butadienyl cobaltacycle (A!B).[11, 12] In the reaction of styrene (1, R = Ph), endo-cyclic b-H elimination could possibly be suppressed by the h3-butadienyl coordination, and reductive elimination could occur to give cyclobutene 3. In the case of 1-decene (4, R = C8H17), however, exo-cyclic b-H elimination from B takes place to form CoH species C in preference to
Scheme 3. Proposed mechanism.
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Scheme 5. Electrocyclic ring opening and Diels–Alder reaction of cyclobutene 7. PMP = para-methoxyphenyl.
by the first Diels–Alder reaction, the second Diels–Alder reaction did not take place during this reaction. When 7 was heated at 60 8C in the presence of dienophile 26, a direct Diels–Alder adduct, 28, was obtained as the sole product in 77 % yield.[18] Both of the Diels–Alder reactions occurred with endo selectivity to form 27 and 28 as single diastereomers. These methodologies enable the synthesis of complex molecules from simple substrates, such as alkenes, 1,3-enynes, and dienophiles, by short and simple synthetic manipulations. Finally, we investigated the synthesis of allenes. As shown in Equation (2), aliphatic alkenes reacted with 1,3-enynes by means of a 1,4-hydroallylation reaction to afford tetrasubstituted allenes.[19] 1,4-Hydrovinylation of 1,3-dienes with alkenes has already been well established by Hilt’s group.[5a–e] The scope of the substrates is summarized in Scheme 6. A 10 mol % loading of the CoBr2/dppp/Zn/ZnI2 (1:1:2:4) catalyst system and two equivalents of alkenes were used. Under the optimized conditions, allene 5 was obtained in 88 % yield. Other aliphatic alkenes, containing phenyl, phthalimido, and acetoxy groups, were compatible with this reaction to give the corresponding allenes 29–32 in moderate to high yields. When 2-methyl-1,5-hexadiene was used as a substrate, only the lesssubstituted alkenyl moiety reacted to give 33 and 34. In each allene synthesis, the Z product was obtained in approximately 90 % purity, but also contained unidentified isomers.[10] On the other hand, alkenes with functional groups at the allylic position were found to undergo 1,2-hydroallylation. For example, allylbenzene and allyloxytrimethylsilane reacted with 2 to give 1,3,6-trienes 35 (46 %) and 36 (55 %), respectively. In addition, the configuration of the separated alkenyl groups in 35 and 36 were exclusively E. In this 1,2-hydroallylation, the five-membered cobaltacycle, rather than the h3-butadienyl isomer, might be involved as an intermediate because the dimerization of alkenes with simple alkynes also gives 1,4-dienes with E configuration.[6a] Although the origin of these different modes of hydroallylation is still unclear, both allenes and 1,3,6-trienes are useful for further transformations. In conclusion, we have demonstrated a cobalt-catalyzed cross-dimerization of 1,3-enyne with simple alkenes. A [2 + 2] cycloaddition occurred, utilizing alkenes with no allylic hydrogen atoms, whereas aliphatic alkenes underwent hydroallyla-
Scheme 4. Cobalt-catalyzed [2 + 2] cycloaddition of alkenes with 1,3-enynes. pin = pinacolate, PMP = para-methoxyphenyl, TBS = tert-butyldimethylsilyl.
described, this [2 + 2] cycloaddition allowed the preparation of cyclobutenes from both unactivated alkenes and 1,3-enynes. To the best of our knowledge, this is the first example of a transition-metal-catalyzed [2 + 2] cycloaddition of simple styrene derivatives, vinylsilane, and vinylborane with alkynes.[16] The resultant 1-alkenylcyclobutene is a good precursor for the cross-conjugated triene, [3]dendralene,[17] by means of the electrocyclic ring opening of the cyclobutene moiety. Heating cyclobutene 7 in toluene at 100 8C for 24 h afforded triene 25 almost quantitatively (Scheme 5). The reaction proceeded with outward rotation of the PMP group, resulting in an E configuration of the benzylidene moiety. Triene 25 reacted with Nmethylmaleimide (26) to furnish bicyclic product 27 in 88 % yield. This Diels–Alder reaction took place exclusively at the less-hindered diene site. Although 27 also has a diene moiety Chem. Eur. J. 2014, 20, 1 – 6
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Communication [2] For reviews on transformations of 1,n-enynes, see: a) C. Aubert, O. Buisine, M. Malacria, Chem. Rev. 2002, 102, 813; b) V. Michelet, P. Y. Toullec, J.-P. GenÞt, Angew. Chem. 2008, 120, 4338; Angew. Chem. Int. Ed. 2008, 47, 4268. [3] For reviews on nickel- and cobalt-catalyzed reactions, see: a) J. Montgomery, Angew. Chem. 2004, 116, 3980; Angew. Chem. Int. Ed. 2004, 43, 3890; b) M. Jeganmohan, C.-H. Cheng, Chem. Eur. J. 2008, 14, 10876; c) W. Hess, J. Treutwein, G. Hilt, Synthesis 2008, 3537. [4] For cobalt-catalyzed cyclodimerization, see: a) J. E. Lyons, H. K. Myers, A. Schneider, Ann. N. Y. Acad. Sci. 1980, 333, 273; b) G. Hilt, F.-X. du Mesnil, Tetrahedron Lett. 2000, 41, 6757; c) G. Hilt, S. Lers, K. Polborn, Isr. J. Chem. 2001, 41, 317; G. Hilt, T. Korn, Tetrahedron Lett. 2001, 42, 2783; d) M. Achard, A. Tenaglia, G. Buono, Org. Lett. 2005, 7, 2353; e) G. Hilt, J. Janikowski, W. Hess, Angew. Chem. 2006, 118, 5328; Angew. Chem. Int. Ed. 2006, 45, 5204; f) M. Achard, M. Mosrin, A. Tenaglia, G. Buono, J. Org. Chem. 2006, 71, 2907; g) G. Hilt, W. Hess, K. Harms, Synthesis 2008, 75; h) H. Clavier, K. Le Jeune, I. De Riggi, A. Tenaglia, G. Buono, Org. Lett. 2011, 13, 308. [5] For cobalt-catalyzed acyclic dimerization, see: a) G. Hilt, F.-X. du Mesnil, S. Lers, Angew. Chem. 2001, 113, 408; Angew. Chem. Int. Ed. 2001, 40, 387; b) G. Hilt, S. Lers, Synthesis 2002, 609; c) M. Arndt, M. Dindarogˇlu, H.-G. Schmalz, G. Hilt, Org. Lett. 2011, 13, 6236; d) L. Kersten, G. Hilt, Adv. Synth. Catal. 2012, 354, 863; e) M. Arndt, M. Dindarogˇlu, H.-G. Schmalz, G. Hilt, Synthesis 2012, 3534; f) C.-C. Wang, P.-S. Lin, C.-H. Cheng, Tetrahedron Lett. 2004, 45, 6203; g) M. A. Bohn, A. Schmidt, G. Hilt, M. Dindarogˇlu, H.-G. Schmalz, Angew. Chem. 2011, 123, 9863; Angew. Chem. Int. Ed. 2011, 50, 9689; h) A. Schmidt, G. Hilt, Org. Lett. 2013, 15, 2708. [6] a) G. Hilt, J. Treutwein, Angew. Chem. 2007, 119, 8653; Angew. Chem. Int. Ed. 2007, 46, 8500; b) S. Mannathan, C.-H. Cheng, Chem. Commun. 2010, 46, 1923. [7] a) U. M. Dzhemilev, R. I. Khusnutdinov, Z. S. Muslimov, G. A. Tolstikov, Bull. Acad. Sci. USSR Div. Chem. Sci. (Engl. Transl.) 1987, 36, 977; b) K. C. Chao, D. K. Rayabarapu, C.-C. Wang, C.-H. Cheng, J. Org. Chem. 2001, 66, 8804; c) J. Treutwein, G. Hilt, Angew. Chem. 2008, 120, 6916; Angew. Chem. Int. Ed. 2008, 47, 6811; intramolecular [2 + 2] cycloaddition of 1,6enyne catalyzed by [CpCo(CO)2] has also been reported, see: d) O. Buisine, C. Aubert, M. Malacria, Chem. Eur. J. 2001, 7, 3517. [8] G. Hilt, A. Paul, J. Treutwein, Org. Lett. 2010, 12, 1536. [9] A. Nishimura, M. Ohashi, S. Ogoshi, J. Am. Chem. Soc. 2012, 134, 15692. [10] The possible isomers of 5 are listed below.
Scheme 6. Cobalt-catalyzed hydroallylation of 1,3-enynes with aliphatic alkenes. PhthN = phthalimido, TBS = tert-butyldimethylsilyl, TMS = trimethylsilyl.
tion. These reactions are highly chemo- and regioselective and can provide synthetically useful cyclobutenes and allenes that were previously difficult to access. We also showed that 1-alkenylcyclobutene is a good substrate for conversion into [3]dendralene and Diels–Alder cycloadducts. Mechanistic studies in our laboratory are currently being focused on clarifying the origin of the reactivities of alkenes in this reaction.
Acknowledgements [11] Utilizing a cobalt(I) precatalyst, CoCl(PPh3)3, cyclobutene 3 was also obtained in 16 % yield without a reducing agent. This observation suggested the involvement of cobalt(I) species in the catalytic cycle. For details, see the Supporting Information. [12] a) P. Mçrschel, J. Janikowski, G. Hilt, G. Frenking, J. Am. Chem. Soc. 2008, 130, 8952; b) L. Fiebig, J. Kuttner, G. Hilt, M. C. Schwarzer, G. Frenking, H.-G. Schmalz, M. Schfer, J. Org. Chem. 2013, 78, 10485. [13] B. Ma, J. K. Snyder, Organometallics 2002, 21, 4688. [14] dppe = 1,3-bis(diphenylphosphino)ethane; rac-BINAP = rac-2,2’-bis(diphenylphosphino)-1,1’-binaphthyl; BIHEP = 2,2’-bis(diphenylphospino)1,1’-biphenyl. [15] F. Pnner, G. Hilt, Chem. Commun. 2012, 48, 3617. [16] Gold-catalyzed [2 + 2] cycloaddition of unactivated highly substituted alkenes with terminal alkynes has been reported, see: V. Lpez-Carrillo, A. M. Echavarren, J. Am. Chem. Soc. 2010, 132, 9292. [17] For a review on dendralenes, see: H. Hopf, M. S. Sherburn, Angew. Chem. 2012, 124, 2346; Angew. Chem. Int. Ed. 2012, 51, 2298. [18] At 100 8C, the ring opening of 7 competed to give a mixture of 27 and 28. For details, see the Supporting Information.
This work was supported by a Grant-in-Aid for Scientists (A) (No. 25708018) and a Grant-in-Aid for Scientific Research on Innovative Area “Molecular Activation Directed toward Straightforward Synthesis” (No. 23105546) from MEXT, and the Asahi Glass Foundation. A.N. expresses his special thanks for the research fellowships for young scientists from the Japan Society for the Promotion of Science (JSPS). Keywords: 1,3-enyenes cyclobutene
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[1] For reviews on cycloaddition, see: a) M. Lautens, W. Klute, W. Tam, Chem. Rev. 1996, 96, 49; b) P. R. Chopade, J. Louie, Adv. Synth. Catal. 2006, 348, 2307; c) P. A. Inglesby, P. A. Evans, Chem. Soc. Rev. 2010, 39, 2791; d) G. Domnguez, J. Prez-Castells, Chem. Soc. Rev. 2011, 40, 3430; e) N. Weding, M. Hapke, Chem. Soc. Rev. 2011, 40, 4525.
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Communication Org. Lett. 2008, 10, 2505; e) T. Nishimura, H. Makino, M. Nagaosa, T. Hayashi, J. Am. Chem. Soc. 2010, 132, 12865.
[19] For examples of transition-metal-catalyzed 1,4-addition of 1,3-enyne, see: a) T. Kusumoto, K. Ando, T. Hiyama, Bull. Chem. Soc. Jpn. 1992, 65, 1280; b) V. Gevorgyan, C. Kadowaki, M. M. Salter, I. Kadota, S. Saito, Y. Yamamoto, Tetrahedron 1997, 53, 9097; c) J. W. Han, N. Tokunaga, T. Hayashi, J. Am. Chem. Soc. 2001, 123, 12915; d) C. Lken, C. Moberg,
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Received: February 17, 2014 Published online on && &&, 0000
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COMMUNICATION & Synthetic Methods A. Nishimura, E. Tamai, M. Ohashi, S. Ogoshi* && – && Synthesis of Cyclobutenes and Allenes by Cobalt-Catalyzed CrossDimerization of Simple Alkenes with 1,3-Enynes
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One catalyst, two possibilities: In the presence of a cobalt/1,3-bis(diphenylphosphino)propane (dppp) catalyst, the [2 + 2] cycloaddition of 1,3-enynes and alkenes with no allylic hydrogen atoms (e.g. styrene) occurred, whereas aliphatic alkenes underwent 1,4-hydroallylation
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into 1,3-enynes (see scheme). From simple substrates, these reactions can provide cyclobutenes and allenes that were previously difficult to access in a highly chemo- and regioselective manner.
2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!
Communication
& Synthetic Methods
Synthesis of Cyclobutenes and Allenes by Cobalt-Catalyzed Cross-Dimerization of Simple Alkenes with 1,3-Enynes Akira Nishimura,[a] Eri Tamai,[a] Masato Ohashi,[a] and Sensuke Ogoshi*[a, b] Abstract: Cobalt-catalyzed cross-dimerization of simple alkenes with 1,3-enynes is reported. A [2 + 2] cycloaddition reaction occurred, with alkenes bearing no allylic hydrogen, by reductive elimination of a h3-butadienyl cobaltacycle. On the other hand, aliphatic alkenes underwent 1,4hydroallylation by means of exo-cyclic b-H elimination. These reactions can provide cyclobutenes and allenes that were previously difficult to access, from simple substrates in a highly chemo- and regioselective manner.
Scheme 1. Cobalt-catalyzed cross-dimerization of alkenes with alkynes.
strained cyclopentene has an interim reactivity between simple alkenes and norbornenes, affording both cyclobutene and 1,4-diene.[8] However, the chemoselectivity mainly depends on the structural nature of the alkenes. Therefore, it is a challenge to develop a transformation that can provide previously inaccessible products beyond conventional reactivity. Herein, we report the cobalt-catalyzed cross-dimerization of simple alkenes with 1,3-enynes to afford cyclobutenes or tetrasubstituted allenes. 1,3-enynes display totally different chemoselectivity compared to that of internal alkynes. We have previously developed a nickel-catalyzed [2 + 2] cycloaddition of alkenes with 1,3-enynes (Scheme 2).[9] On the
Oxidative cyclization of two p components at a transitionmetal center to form a metallacycle is a fundamental reaction in the field of organometallic chemistry. This process is accepted as the key step for a variety of synthetic methods, such as cycloaddition, linear oligomerization, reductive coupling, and multicomponent reactions.[1–3] Catalytic variants of these transformations are frequently achieved with late transition metals, of which cobalt is attractive because it can efficiently catalyze the dimerization of electronically unbiased unsaturated hydrocarbons.[4, 5] The groups of Hilt and Cheng have demonstrated the cross-dimerization of simple alkenes with internal alkynes, in the presence of a cobalt(I)/1,3-bis(diphenylphosphino)propane (dppp) catalyst, to furnish linear dienes (Scheme 1).[6] These cross-dimerization reactions are proposed to proceed via a cobaltacyclopentene intermediate, which undergoes b-H elimination, followed by reductive elimination. The difference in chemoselectivity between the formation of 1,3-dienes by means of endo-cyclic b-H elimination and 1,4-dienes, by means of exo-cyclic b-H elimination occurs in the absence and in the presence of allylic hydrogen atoms on the alkene substrates. On the other hand, [2 + 2] cycloaddition occurs in the reaction of highly strained bicyclic alkenes, such as norbornene, with alkynes by means of direct reductive elimination from the corresponding cobaltacycle.[7] Hilt et al. also reported that less-
Scheme 2. Nickel-catalyzed [2 + 2] cycloaddition of electron-deficient alkenes with 1,3-enynes. EWG = electron-withdrawing group
basis of a stoichiometric study, the key step of this [2 + 2] cycloaddition was the formation of an h3-butadienyl nickelacycle, which might prevent undesired pathways, such as b-H elimination and the insertion of another p substrate. On comparison with electron-deficient alkenes, unactivated simple alkenes are less reactive in the nickel-catalyzed reaction, and the resultant product was a mixture of isomers. Thus, we next focused on the cobalt catalyst, which has both good reactivity and selectivity in the cross-dimerization of unactivated alkenes with alkynes. We assumed that, as with nickel catalysis, if the oxidative cyclization of alkenes with 1,3-enynes at the cobalt center can occur to form a h3-butadienyl intermediate, then b-H elimination could be avoided, and cyclobutenes could be provided by means of reductive elimination. In fact, two examples can
[a] A. Nishimura, E. Tamai, Dr. M. Ohashi, Prof. Dr. S. Ogoshi Department of Applied Chemistry Faculty of Engineering, Osaka University Suita, Osaka 565-0871 (Japan) Fax: (+ 81) 6-6879-7394 E-mail: [email protected] [b] Prof. Dr. S. Ogoshi JST, Advanced Catalytic Transformation Program for Carbon Utilization (ACT-C) Suita, Osaka 565-0871 (Japan) Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201402218. Chem. Eur. J. 2014, 20, 1 – 6
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Communication be found in the literature, showing that 1,3-enynes facilitate [2 + 2] cycloaddition with alkenes under cobalt catalysis.[7a, 8] To elucidate our working hypothesis, we first examined the reactions of two different types of alkenes with a 1,3-enyne. Based on the reaction conditions developed by the groups of Hilt and Cheng,[6] a CoBr2/dppp/Zn/ZnI2 (ratio 1:1:4:4) catalyst system was used. As expected, styrene (1) reacted with 2methyl-1-hexen-3-yne (2) in the presence of the cobalt catalyst to give desired cyclobutene 3 in 80 % yield [Eq. (1)].
CC reductive elimination. Then, C undergoes reductive elimination to give allene 5. According to the preliminary results and mechanistic hypothesis, alkenes with no allylic hydrogen atoms have the potential to undergo [2 + 2] cycloaddition with 1,3-enynes. Several optimizations of reaction conditions were investigated based on Equation (1) (for details, see the Supporting Information).[13] An equimolar, or a slightly excessive, amount of 1 was enough to obtain 3 in a sufficient yield. A screening of ligands revealed that only dppp was suitable for catalytic conversion into the product. The reaction with dppe, rac-BINAP, or BIHEP gave cyclobutene 3 in approximately 10 % yield.[14] The use of other mono- or bidentate ligands was unsuccessful. Regarding cobalt(II) salts, CoBr2, CoI2, and Co(OAc)2 were applicable to this [2 + 2] cycloaddition, whereas CoCl2 was less effective. After further optimizations, we selected the reaction conditions as follows: CoBr2/dppp/Zn/ZnI2 (1:1:1:2) as the catalyst, 2 mol % catalyst loading, and CH2Cl2 as the solvent. Next, the [2 + 2] cycloaddition of styrene derivatives with enyne 2 was examined (Scheme 4). Under the optimized conditions, cyclobutene 3 was obtained in 79 % isolated yield. The reaction of para-methylstyrene and para-methoxystyrene gave 6 and 7 in 83 and 80 % yield, respectively. Halogen atoms (F, Cl, and Br) at the para-position were compatible with this [2 + 2] cycloaddition, and provided the corresponding cyclobutenes 8–10 in high yields. These halogen substituents, Br and Cl substituents in particular, can be further functionalized by crosscoupling reactions. Among the meta-substituted styrenes employed, the reaction of meta-methylstyrene was comparable to the corresponding para-substituted example, giving 11 in 83 % yield. On the other hand, electron-withdrawing groups, such as CF3 and F groups, decreased the reactivity to afford 12 and 13 in 23 and 43 % yields, respectively. ortho-Tolyl-substituted 14 was obtained in only 8 % yield, probably owing to steric hindrance. However, neither ortho-methoxy- nor ortho-chlorosubstituents diminished the reactivity and provided compounds 15 (91 %) and 16 (51 %), respectively. In these cases, the reactions might be facilitated by chelation to the cobalt center through an oxygen- or chlorine atom. para-Cyanostyrene and 2-vinylpyridne did not react at all, probably owing to the deactivation of the catalyst by the strong coordination of the nitrogen atom. Although the yields were more modest, vinylboronate and vinylsilane reacted to provide cyclobutenes 17 and 18, which can be utilized for further transformations, such as cross-coupling, allylic substitution, and oxidation. The scope of 1,3-enynes was also investigated. The reaction of enynes bearing longer alkyl chains, and chloro- or silyloxy substituents afforded the corresponding cyclobutenes 19, 20, and 21 in moderate to high yields. With 5 mol % catalyst loading, 1,5-dien-3-yne also reacted to give 1,2-diisopropenylcyclobutene 22 in 49 % yield. 1,3-Enynes bearing a naked vinyl group were also applied to this reaction, affording 23 (50 %) and 24 (34 %) in the presence of 5 mol % catalyst loading. However, a competing homodimerization of enynes was also observed.[15] Although the yield of the product was not improved, the slow addition of the enyne through a syringe drive suppressed the formation of the enyne dimer in the case of 23. As
In contrast to the nickel-catalyzed reaction, the cobalt-catalyzed [2 + 2] cycloaddition proceeded even at room temperature and 3 was obtained as a single regioisomer. On the other hand, the reaction of 1-decene (4) with 2 gave no cyclobutene under the same conditions; instead, tetrasubstituted allene 5 was obtained as the major product in 76 % yield, accompanied by a small amount of unidentified isomers [Eq. (2)].[10] Although the cobalt-catalyzed cross-dimerization of alkenes with alkynes gives (E,E)-dienes,[6] the configuration of the alkenyl moiety of 5 was Z. The difference in the reactivity of alkenes 1 and 4, under cobalt catalysis, can be rationalized as described in Scheme 3. In both cases, the reaction is initiated by the oxidative cyclization of an alkene with a 1,3-enyne at the cobalt(I) center, forming a h3-butadienyl cobaltacycle (A!B).[11, 12] In the reaction of styrene (1, R = Ph), endo-cyclic b-H elimination could possibly be suppressed by the h3-butadienyl coordination, and reductive elimination could occur to give cyclobutene 3. In the case of 1-decene (4, R = C8H17), however, exo-cyclic b-H elimination from B takes place to form CoH species C in preference to
Scheme 3. Proposed mechanism.
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Scheme 5. Electrocyclic ring opening and Diels–Alder reaction of cyclobutene 7. PMP = para-methoxyphenyl.
by the first Diels–Alder reaction, the second Diels–Alder reaction did not take place during this reaction. When 7 was heated at 60 8C in the presence of dienophile 26, a direct Diels–Alder adduct, 28, was obtained as the sole product in 77 % yield.[18] Both of the Diels–Alder reactions occurred with endo selectivity to form 27 and 28 as single diastereomers. These methodologies enable the synthesis of complex molecules from simple substrates, such as alkenes, 1,3-enynes, and dienophiles, by short and simple synthetic manipulations. Finally, we investigated the synthesis of allenes. As shown in Equation (2), aliphatic alkenes reacted with 1,3-enynes by means of a 1,4-hydroallylation reaction to afford tetrasubstituted allenes.[19] 1,4-Hydrovinylation of 1,3-dienes with alkenes has already been well established by Hilt’s group.[5a–e] The scope of the substrates is summarized in Scheme 6. A 10 mol % loading of the CoBr2/dppp/Zn/ZnI2 (1:1:2:4) catalyst system and two equivalents of alkenes were used. Under the optimized conditions, allene 5 was obtained in 88 % yield. Other aliphatic alkenes, containing phenyl, phthalimido, and acetoxy groups, were compatible with this reaction to give the corresponding allenes 29–32 in moderate to high yields. When 2-methyl-1,5-hexadiene was used as a substrate, only the lesssubstituted alkenyl moiety reacted to give 33 and 34. In each allene synthesis, the Z product was obtained in approximately 90 % purity, but also contained unidentified isomers.[10] On the other hand, alkenes with functional groups at the allylic position were found to undergo 1,2-hydroallylation. For example, allylbenzene and allyloxytrimethylsilane reacted with 2 to give 1,3,6-trienes 35 (46 %) and 36 (55 %), respectively. In addition, the configuration of the separated alkenyl groups in 35 and 36 were exclusively E. In this 1,2-hydroallylation, the five-membered cobaltacycle, rather than the h3-butadienyl isomer, might be involved as an intermediate because the dimerization of alkenes with simple alkynes also gives 1,4-dienes with E configuration.[6a] Although the origin of these different modes of hydroallylation is still unclear, both allenes and 1,3,6-trienes are useful for further transformations. In conclusion, we have demonstrated a cobalt-catalyzed cross-dimerization of 1,3-enyne with simple alkenes. A [2 + 2] cycloaddition occurred, utilizing alkenes with no allylic hydrogen atoms, whereas aliphatic alkenes underwent hydroallyla-
Scheme 4. Cobalt-catalyzed [2 + 2] cycloaddition of alkenes with 1,3-enynes. pin = pinacolate, PMP = para-methoxyphenyl, TBS = tert-butyldimethylsilyl.
described, this [2 + 2] cycloaddition allowed the preparation of cyclobutenes from both unactivated alkenes and 1,3-enynes. To the best of our knowledge, this is the first example of a transition-metal-catalyzed [2 + 2] cycloaddition of simple styrene derivatives, vinylsilane, and vinylborane with alkynes.[16] The resultant 1-alkenylcyclobutene is a good precursor for the cross-conjugated triene, [3]dendralene,[17] by means of the electrocyclic ring opening of the cyclobutene moiety. Heating cyclobutene 7 in toluene at 100 8C for 24 h afforded triene 25 almost quantitatively (Scheme 5). The reaction proceeded with outward rotation of the PMP group, resulting in an E configuration of the benzylidene moiety. Triene 25 reacted with Nmethylmaleimide (26) to furnish bicyclic product 27 in 88 % yield. This Diels–Alder reaction took place exclusively at the less-hindered diene site. Although 27 also has a diene moiety Chem. Eur. J. 2014, 20, 1 – 6
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Communication [2] For reviews on transformations of 1,n-enynes, see: a) C. Aubert, O. Buisine, M. Malacria, Chem. Rev. 2002, 102, 813; b) V. Michelet, P. Y. Toullec, J.-P. GenÞt, Angew. Chem. 2008, 120, 4338; Angew. Chem. Int. Ed. 2008, 47, 4268. [3] For reviews on nickel- and cobalt-catalyzed reactions, see: a) J. Montgomery, Angew. Chem. 2004, 116, 3980; Angew. Chem. Int. Ed. 2004, 43, 3890; b) M. Jeganmohan, C.-H. Cheng, Chem. Eur. J. 2008, 14, 10876; c) W. Hess, J. Treutwein, G. Hilt, Synthesis 2008, 3537. [4] For cobalt-catalyzed cyclodimerization, see: a) J. E. Lyons, H. K. Myers, A. Schneider, Ann. N. Y. Acad. Sci. 1980, 333, 273; b) G. Hilt, F.-X. du Mesnil, Tetrahedron Lett. 2000, 41, 6757; c) G. Hilt, S. Lers, K. Polborn, Isr. J. Chem. 2001, 41, 317; G. Hilt, T. Korn, Tetrahedron Lett. 2001, 42, 2783; d) M. Achard, A. Tenaglia, G. Buono, Org. Lett. 2005, 7, 2353; e) G. Hilt, J. Janikowski, W. Hess, Angew. Chem. 2006, 118, 5328; Angew. Chem. Int. Ed. 2006, 45, 5204; f) M. Achard, M. Mosrin, A. Tenaglia, G. Buono, J. Org. Chem. 2006, 71, 2907; g) G. Hilt, W. Hess, K. Harms, Synthesis 2008, 75; h) H. Clavier, K. Le Jeune, I. De Riggi, A. Tenaglia, G. Buono, Org. Lett. 2011, 13, 308. [5] For cobalt-catalyzed acyclic dimerization, see: a) G. Hilt, F.-X. du Mesnil, S. Lers, Angew. Chem. 2001, 113, 408; Angew. Chem. Int. Ed. 2001, 40, 387; b) G. Hilt, S. Lers, Synthesis 2002, 609; c) M. Arndt, M. Dindarogˇlu, H.-G. Schmalz, G. Hilt, Org. Lett. 2011, 13, 6236; d) L. Kersten, G. Hilt, Adv. Synth. Catal. 2012, 354, 863; e) M. Arndt, M. Dindarogˇlu, H.-G. Schmalz, G. Hilt, Synthesis 2012, 3534; f) C.-C. Wang, P.-S. Lin, C.-H. Cheng, Tetrahedron Lett. 2004, 45, 6203; g) M. A. Bohn, A. Schmidt, G. Hilt, M. Dindarogˇlu, H.-G. Schmalz, Angew. Chem. 2011, 123, 9863; Angew. Chem. Int. Ed. 2011, 50, 9689; h) A. Schmidt, G. Hilt, Org. Lett. 2013, 15, 2708. [6] a) G. Hilt, J. Treutwein, Angew. Chem. 2007, 119, 8653; Angew. Chem. Int. Ed. 2007, 46, 8500; b) S. Mannathan, C.-H. Cheng, Chem. Commun. 2010, 46, 1923. [7] a) U. M. Dzhemilev, R. I. Khusnutdinov, Z. S. Muslimov, G. A. Tolstikov, Bull. Acad. Sci. USSR Div. Chem. Sci. (Engl. Transl.) 1987, 36, 977; b) K. C. Chao, D. K. Rayabarapu, C.-C. Wang, C.-H. Cheng, J. Org. Chem. 2001, 66, 8804; c) J. Treutwein, G. Hilt, Angew. Chem. 2008, 120, 6916; Angew. Chem. Int. Ed. 2008, 47, 6811; intramolecular [2 + 2] cycloaddition of 1,6enyne catalyzed by [CpCo(CO)2] has also been reported, see: d) O. Buisine, C. Aubert, M. Malacria, Chem. Eur. J. 2001, 7, 3517. [8] G. Hilt, A. Paul, J. Treutwein, Org. Lett. 2010, 12, 1536. [9] A. Nishimura, M. Ohashi, S. Ogoshi, J. Am. Chem. Soc. 2012, 134, 15692. [10] The possible isomers of 5 are listed below.
Scheme 6. Cobalt-catalyzed hydroallylation of 1,3-enynes with aliphatic alkenes. PhthN = phthalimido, TBS = tert-butyldimethylsilyl, TMS = trimethylsilyl.
tion. These reactions are highly chemo- and regioselective and can provide synthetically useful cyclobutenes and allenes that were previously difficult to access. We also showed that 1-alkenylcyclobutene is a good substrate for conversion into [3]dendralene and Diels–Alder cycloadducts. Mechanistic studies in our laboratory are currently being focused on clarifying the origin of the reactivities of alkenes in this reaction.
Acknowledgements [11] Utilizing a cobalt(I) precatalyst, CoCl(PPh3)3, cyclobutene 3 was also obtained in 16 % yield without a reducing agent. This observation suggested the involvement of cobalt(I) species in the catalytic cycle. For details, see the Supporting Information. [12] a) P. Mçrschel, J. Janikowski, G. Hilt, G. Frenking, J. Am. Chem. Soc. 2008, 130, 8952; b) L. Fiebig, J. Kuttner, G. Hilt, M. C. Schwarzer, G. Frenking, H.-G. Schmalz, M. Schfer, J. Org. Chem. 2013, 78, 10485. [13] B. Ma, J. K. Snyder, Organometallics 2002, 21, 4688. [14] dppe = 1,3-bis(diphenylphosphino)ethane; rac-BINAP = rac-2,2’-bis(diphenylphosphino)-1,1’-binaphthyl; BIHEP = 2,2’-bis(diphenylphospino)1,1’-biphenyl. [15] F. Pnner, G. Hilt, Chem. Commun. 2012, 48, 3617. [16] Gold-catalyzed [2 + 2] cycloaddition of unactivated highly substituted alkenes with terminal alkynes has been reported, see: V. Lpez-Carrillo, A. M. Echavarren, J. Am. Chem. Soc. 2010, 132, 9292. [17] For a review on dendralenes, see: H. Hopf, M. S. Sherburn, Angew. Chem. 2012, 124, 2346; Angew. Chem. Int. Ed. 2012, 51, 2298. [18] At 100 8C, the ring opening of 7 competed to give a mixture of 27 and 28. For details, see the Supporting Information.
This work was supported by a Grant-in-Aid for Scientists (A) (No. 25708018) and a Grant-in-Aid for Scientific Research on Innovative Area “Molecular Activation Directed toward Straightforward Synthesis” (No. 23105546) from MEXT, and the Asahi Glass Foundation. A.N. expresses his special thanks for the research fellowships for young scientists from the Japan Society for the Promotion of Science (JSPS). Keywords: 1,3-enyenes cyclobutene
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[1] For reviews on cycloaddition, see: a) M. Lautens, W. Klute, W. Tam, Chem. Rev. 1996, 96, 49; b) P. R. Chopade, J. Louie, Adv. Synth. Catal. 2006, 348, 2307; c) P. A. Inglesby, P. A. Evans, Chem. Soc. Rev. 2010, 39, 2791; d) G. Domnguez, J. Prez-Castells, Chem. Soc. Rev. 2011, 40, 3430; e) N. Weding, M. Hapke, Chem. Soc. Rev. 2011, 40, 4525.
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Communication Org. Lett. 2008, 10, 2505; e) T. Nishimura, H. Makino, M. Nagaosa, T. Hayashi, J. Am. Chem. Soc. 2010, 132, 12865.
[19] For examples of transition-metal-catalyzed 1,4-addition of 1,3-enyne, see: a) T. Kusumoto, K. Ando, T. Hiyama, Bull. Chem. Soc. Jpn. 1992, 65, 1280; b) V. Gevorgyan, C. Kadowaki, M. M. Salter, I. Kadota, S. Saito, Y. Yamamoto, Tetrahedron 1997, 53, 9097; c) J. W. Han, N. Tokunaga, T. Hayashi, J. Am. Chem. Soc. 2001, 123, 12915; d) C. Lken, C. Moberg,
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Received: February 17, 2014 Published online on && &&, 0000
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COMMUNICATION & Synthetic Methods A. Nishimura, E. Tamai, M. Ohashi, S. Ogoshi* && – && Synthesis of Cyclobutenes and Allenes by Cobalt-Catalyzed CrossDimerization of Simple Alkenes with 1,3-Enynes
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One catalyst, two possibilities: In the presence of a cobalt/1,3-bis(diphenylphosphino)propane (dppp) catalyst, the [2 + 2] cycloaddition of 1,3-enynes and alkenes with no allylic hydrogen atoms (e.g. styrene) occurred, whereas aliphatic alkenes underwent 1,4-hydroallylation
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into 1,3-enynes (see scheme). From simple substrates, these reactions can provide cyclobutenes and allenes that were previously difficult to access in a highly chemo- and regioselective manner.
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