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Synlett 2016; 27(03): 432-436
DOI: 10.1055/s-0035-1560587
letter
© Georg Thieme Verlag Stuttgart · New York

Bisallylation of Zirconacyclopentenes and Ring-Closing Metathesis: A Route to Eight-Membered-Ring Compounds

Nikola Topolovčan
Department of Organic Chemistry, Faculty of Science, Charles University in Prague, Hlavova 8, 128 43 Praha 2, Czech Republic   Email: martin.kotora@natur.cuni.cz
,
Illia Panov
Department of Organic Chemistry, Faculty of Science, Charles University in Prague, Hlavova 8, 128 43 Praha 2, Czech Republic   Email: martin.kotora@natur.cuni.cz
,
Martin Kotora*
Department of Organic Chemistry, Faculty of Science, Charles University in Prague, Hlavova 8, 128 43 Praha 2, Czech Republic   Email: martin.kotora@natur.cuni.cz
› Author Affiliations
Further Information

Publication History

Received: 16 September 2015

Accepted after revision: 04 October 2015

Publication Date:
09 November 2015 (online)

 
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Dedicated to Professor Ei-ichi Negishi on the occasion of his 80th birthday

Abstract

The cyclization of various enynes with the Negishi reagent provides the corresponding bicyclic zirconacyclopentenes, which after exposure to allyl chloride in the presence of a catalytic amount of copper(I) chloride, undergo bisallylation to furnish 1,9-decadienes in good yields (42–89%). The dienes are subjected to ring-closing metathesis to afford bicyclic compounds with [6.3.0]bicycloundecane (8,5-fused ring system) or [6.4.0]bicyclododecane (8,6-fused ring system) frameworks in good to excellent yields (52–92%). Selective monoallylation of a selected zirconacyclopentene followed by carboxyethylation with ethyl chloroformate gives rise to the corresponding ester, which after metalation and reaction with allyl bromide, furnishes a 1,9-decadiene. Ring-closing metathesis then yields the expected eight-membered cyclic product in 92% yield. This procedure constitutes a new pathway to bicyclic carbocyclic systems starting from 1,ω-enynes.


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Key words

zirconium - allylation - metathesis - enynes - cyclization

Enynes are useful synthetic building blocks that can react with different low-valent transition-metal compounds to give rise to the corresponding metallacyclopentenes. These metallacyclopentenes can be used in various transformations to afford products with higher molecular complexity.[1] One such class of metallacycles, the zirconacyclopentenes, are easily prepared from enynes and the Negishi reagent.[2] These metallacycles have been employed over several decades as synthetically useful intermediates. A distinct feature of their reactivity is their ability to undergo carbonylation with carbon monoxide (CO) to the give the corresponding cyclopentenones.[3] This approach has been used in the synthesis of various natural products such as pentalenic acid,[4] carbacyclin,[5] iridomyrmecine,[6] and tecomanine.[7]

Attention has been devoted to selective reactions at the sp3 C–Zr or sp2 C–Zr bonds in zirconacyclopentenes, allowing regioselective functionalization. Early studies of the reactivity of zirconacyclopentenes showed that either the sp3 C–Zr or sp2 C–Zr bond can preferentially react with various electrophiles when judicious choice of the reaction conditions are met. In fact, the results indicated that electrophiles such as iodine, aldehydes, alkyl halides, and trimethylstannyl halides reacted preferentially with the sp3 C–Zr bond.[8] These results were later utilized in reactions of zirconacyclopentenes with aldehydes. These examples encompass reactions of aldehydes, either with extrusion of ethylene yielding allylic alcohols,[9] or by insertion into the sp3 C–Zr bond to give rise to pent-4-en-1-ols and derivatives.[10] It has been recently shown that aldehyde insertion can be combined with intramolecular arylation to provide compounds possessing the condensed 5(6),7,6-ring framework.[11] Further expansion of these processes was followed by development of copper(I)-catalyzed C–C bond formation. In this case, transmetalation with copper(I) chloride (CuCl) proceeded preferentially at the sp2 C–Zr bond. Typical examples include reactions of zirconacyclopentenes with various unsaturated compounds with extrusion of an ethylene moiety followed by copper(I) chloride catalyzed allylation of the sp2 C–Zr bond,[12] copper(I) chloride catalyzed allylation of the sp2 C–Zr bond in the zirconacyclopentenes (which clearly showed that CuCl preferentially transmetalates the sp2 C–Zr bond in the presence of the sp3 C–Zr bond),[13] selective copper(I) chloride catalyzed acylation of the sp2 C–Zr bond,[14] copper(I) chloride catalyzed conjugate addition of the sp2 C–Zr bond to unsaturated ketones,[15] and selective unsymmetrical copper(I) chloride catalyzed bisalkynylation of zirconacyclopentenes using haloalkynes.[16]

As far as allylation of zirconacycles to form carbocyclic compounds is concerned, dual inter–intramolecular allylation of zirconacyclopentadienes with suitably substituted allylic halides has been used for the synthesis of vinylcyclohexadienes and cycloheptadienes.[17] The two-fold intermolecular allylation of zirconacyclopentadienes to provide the corresponding 1,9-decadienes, with subsequent cyclization into the corresponding 8,5-fused-ring compounds using the Negishi reagent has also been reported.[18] Interestingly, the bisallylation of zirconacyclopentenes and zirconacyclopentanes has not been reported to date, despite the fact that such compounds might be interesting intermediates for the synthesis of eight-membered-ring compounds upon ring-closing metathesis.

With respect to our interest in using organozirconium chemistry as a key tool for C–C bond formation in syntheses of natural products,[19] we envisaged that double allylation of bicyclic zirconacyclopentenes would provide access to the corresponding 1,9-decadienes, which after ring-closing metathesis (RCM), would yield bicyclic compounds possessing the condensed 5(6),8-ring framework (Scheme [1]). Since bisallylations of several zirconacycles as well as the feasibility of cyclizations of various 1,9-decadienes into eight-membered-ring compounds have been demonstrated previously,[20] we expected that the proposed reaction sequence would be feasible.

Zoom Image
Scheme 1 Retrosynthetic analysis for the formation of a [6.3.0]bicycloundecane framework

It should be mentioned that compounds possessing the eight-membered-ring framework can be found in a number of natural compounds, and their syntheses have attracted considerable attention.[21] Some prominent representatives are asteriscanolide (isolated from the plant, Asteriscus aquaticus),[22] asteriscane (a constituent of the Hainan aeolid nudibranch, Phyllodesmium magnum),[23] and capillosanane A (a constituent of the soft coral, Sinularia capillosa) (Figure [1]).[24] Other examples include taxol, gomisin-G, and spartidienedione.[25]

Zoom Image
Figure 1 Examples of natural products containing an eight-membered-ring framework

At the outset, a series of differently substituted 1,6- and 1,7-enynes 1 was prepared using standard protocols (see the Supporting Information). Their cyclization to give the corresponding zirconacyclopentenes 2 was achieved using the Negishi reagent.[3] Next, four equivalents of allyl chloride were added along with a catalytic amount of copper(I) chloride (20 mol%), and the reaction mixture was stirred at 25 °C for 12 hours. In almost all the cases, the bisallylation proceeded quantitatively and, after work-up and isolation, furnished the corresponding 1,9-decadienes 4 in good yields (42–89%) (Scheme [2]). Since it has been previously demonstrated that preferential transmetalation proceeds at the sp2 C–Zr bond, there is no doubt that this reaction proceeds through the formation of a monoallylated organozirconium intermediate 3, which then undergoes a second transmetalation and allylation to give the final product. It is worth noting that the cyclization of benzyl (Bn) or tert-butyldimethylsilyl (TBS) protected enynes 1i and 1j proceeded stereoselectively to provide two diastereoisomeric zirconacyclopentenes (the oxidative dimerization of the corresponding enynes proceeded with the same stereoselectivity as those of the Ti-mediated reactions[26]), which after reaction with allyl chloride provided the corresponding diastereoisomeric 1,9-decadienes in good yields and with >98% stereoselectivity.

Zoom Image
Scheme 2 Bisallylation of zirconacyclopentenes 2 with allyl chloride

It should also be mentioned that selective bisallylation using two different allyl halides was also attempted. However, despite the fact that the selective monoallylation of 2a could be achieved at –10 °C, as was confirmed by hydrolysis of the formed monoallylated organometallic species 3a to give 5a (see the Supporting Information), subsequent addition of crotyl halide did not give the desired product. Instead, an intractable mixture of compounds was formed. 1H NMR spectroscopic analysis of the reaction mixture revealed only the presence of the allylated product 4a, which is the product of the reaction of the sp3 C–Zr bond with unreacted allyl halide.

Since it has been demonstrated that ring-closing metathesis of dienes can be used for the synthesis of cyclooctanoids,[20] we proposed that this process might also be applied to 1,9-decadienes 4, prepared by double allylation of the corresponding zirconacyclopentenes (Scheme [3]). At the outset, ring-closing metathesis of 4a was tested with several commonly used ruthenium catalysts (5 mol%), including the Grubbs first-generation catalyst (G I),[27] the Grubbs second-generation catalyst (G II),[28] the Hoveyda–Grubbs first-generation catalyst (H–G I),[29] and the Hoveyda–Grubbs second-generation catalyst (H–G II)[30] (Scheme [3]); the cyclization proceeded in the presence of all of these catalysts to give the corresponding 5,8-fused ring compound 6a in yields of 99%, 99%, 82%, and 64% (determined by 1H NMR spectroscopy), respectively. Although the first two catalysts displayed the same activity, for practical reasons,[31] the cyclizations to give products 6b–j were carried out with catalyst G II. Ring-closing metathesis proceeded uneventfully in most cases to furnish the desired compounds possessing an eight-membered ring in good yields ranging from 52–92%.

Zoom Image
Scheme 3 Ring-closing metathesis of 1,9-decadienes 4 to give cyclooctadienes 6; Grubbs 2nd generation (G II) catalyst unless otherwise mentioned. 1H NMR yields are in parentheses. a Obtained as complex mixture; the yield was not determined. b nr = no reaction.

Although it was evident that the ring-closing metathesis of 4f had proceeded, the expected product was formed as part of a complex mixture from which it was not possible to isolate as an analytically pure material. The 1H NMR spectrum of the reaction mixture indicated that the desired compound had formed in 15% yield, accompanied by a number of intractable products. Surprisingly, the ring-closing metathesis of 4h did not proceed with any of the above-mentioned ruthenium catalysts and only unreacted starting material was isolated from the reaction mixture.

Since we had observed that the monoallylation of zirconacyclopentene 2a with allyl chloride to give 3a was possible, we decided to explore a different pathway for the selective introduction of different functionalities, namely allyl and ester groups. Although previous studies showed that selective monoallylation required only a catalytic amount of copper(I) chloride, we found that improved results could be obtained by using a stoichiometric amount of the catalyst. Hence, the reaction of 2a with allyl chloride and copper(I) chloride (at –10 °C for 12 h) gave, almost quantitatively, organozirconium compound 3a. Next, ethyl chloroformate was added and the mixture was left to stir at 25 °C for 12 hours. After work-up, compound 7 was obtained in a reasonable 41% yield (Scheme [4]). Metalation of this product with lithium diisopropylamide (LDA) followed by alkylation with allyl bromide gave rise to substituted 1,9-decadiene 8 in 75% yield as an inseparable 4:1 diastereoisomeric mixture. The ensuing ring-closing metathesis under the previously used conditions furnished bicyclic compound 9 as a 4:1 diastereoisomeric mixture in a very satisfying yield of 92%.

Zoom Image
Scheme 4 Synthesis of 1,9-decadiene 8 and its ring-closing metathesis to give 9

In conclusion, bisallylations of various zirconacyclopentenes, obtained by reductive cyclizations of enynes with the Negishi reagent [Cp2Zr(n-Bu)2], gave rise to the corresponding 1,9-decadienes.[32] These underwent ring-closing metathesis in the presence of a catalytic amount of the Grubbs second generation catalyst (G II) to form bicyclic compounds possessing [8.5.0]bicycloundecadiene or [8.6.0]bicyclododecadiene frameworks.[33] We believe that this methodology might represent a useful synthetic tool for the synthesis of more complex natural compounds belonging to the astericanolide family.


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Acknowledgment

This work was supported by the Czech Science Foundation (project No. 13-15915S) and the Charles University Grant Agency (project No. 1132/2015). The authors thank Lach-Ner s.r.o. for generous gifts of chemicals as a part of the award given to M.K.

Supporting Information

    Supporting information for this article is available online at http://dx.doi.org.accesdistant.sorbonne-universite.fr/10.1055/s-0035-1560587.
  • Supporting Information

Primary Data

    Primary data for this article are available online at http://www.thieme-connect­.com/products/ejournals/journal/10.1055/s-00000083 and can be cited using the following DOI: 10.4125/pd0073th.
  • Primary Data

  • References and Notes

  • 1 Aubert C, Buisine O, Malacria M. Chem. Rev. 2002; 102: 813
    Search in Google Scholar
  • 4 Agnel G, Negishi E. J. Am. Chem. Soc. 1991; 113: 7424
    CrossrefSearch in Google Scholar
  • 5 Negishi E, Pour M, Cederbaum FE, Kotora M. Tetrahedron 1998; 54: 7057
    CrossrefSearch in Google Scholar
  • 6 Agnel G, Owczarczyk Z, Negishi E. Tetrahedron Lett. 1992; 33: 1543
    CrossrefSearch in Google Scholar
  • 7 Kemp MI, Whitby RJ, Coote SJ. Synthesis 1998; 552
    Thieme Connect
    • 8a Takahashi T, Aoyagi K, Hara R, Suzuki N. J. Chem. Soc., Chem. Commun. 1993; 1042
    • 8b Takahashi T, Aoyagi K, Kondakov DY. J. Chem. Soc., Chem. Commun. 1994; 747
    • 8c Aoyagi K, Hara R, Kondakov DY, Kasai K, Suzuki N, Takahashi T. Inorg. Chim. Acta 1994; 220: 319
      CrossrefSearch in Google Scholar
  • 11 Topolovčan N, Panov I, Kotora M. Eur. J. Org. Chem. 2015; 2868
  • 12 Takahashi T, Kotora M, Kasai K, Suzuki N. Tetrahedron Lett. 1994; 35: 5685
    CrossrefSearch in Google Scholar
  • 13 Kasai K, Kotora M, Suzuki N, Takahashi T. J. Chem. Soc., Chem. Commun. 1995; 109
  • 14 Takahashi T, Xi Z, Kotora M, Xi C. Tetrahedron Lett. 1996; 37: 7521
    CrossrefSearch in Google Scholar
  • 15 Lipshutz BH, Seki M. Tetrahedron 2005; 51: 4407
    Search in Google Scholar
  • 16 Liu Y, Xi C, Hara R, Nakajima K, Yamazaki A, Kotora M, Takahashi T. J. Org. Chem. 2000; 65: 6951
    CrossrefSearch in Google Scholar
  • 17 Kotora M, Umeda C, Ishida T, Takahashi T. Tetrahedron Lett. 1997; 38: 8355
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      • For a review, see:
    • 20a Prunet J. Eur. J. Org. Chem. 2011; 3634-3647

      • For other typical examples, see:
    • 20b Michaut A, Miranda-García S, Menéndez JC, Coquerel Y, Rodriguez J. Eur. J. Org. Chem. 2008; 4988
    • 20c Dowling MS, Vanderwal CD. J. Org. Chem. 2010; 75: 6908
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  • 22 San Feliciano A, Barrero AF, Medarde M, Miguel del Corral JM, Aramburu A, Perales A, Fayos J. Tetrahedron Lett. 1985; 26: 2369
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  • 23 Mao S.-C, Gavagnin M, Mollo E, Guo Y.-W. Biochem. Syst. Ecol. 2011; 39: 408
    CrossrefSearch in Google Scholar
  • 24 Chen D, Chen W, Liu D, van Ofwegen L, Proksch P, Li W. J. Nat. Prod. 2013; 76: 1753
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  • 26 Urabe H, Suzuki K, Sato F. J. Am. Chem. Soc. 1997; 119: 10014
    CrossrefSearch in Google Scholar
  • 28 Scholl M, Ding S, Lee CW, Grubbs RH. Org. Lett. 1999; 1: 953
    Search in Google Scholar
  • 29 Kingsbury JS, Harrity JP. A, Bonitatebus PJ. Jr, Hoveyda AH. J. Am. Chem. Soc. 1999; 121: 791
    Search in Google Scholar
  • 31 As a result of the low polarity of the starting enyne, it was difficult to separate and purify product 4a from traces of the G I catalyst.
  • 32 (E)-{1-[2-(But-3-en-1-yl)cyclopentylidene]but-3-en-1-yl}benzene (4a); Typical Example To a solution of bis(cyclopentadienyl)zirconium dichloride (0.350 g, 1.20 mmol) in dry THF (7 mL) at –78 °C was added dropwise n-BuLi (1.50 mL, 1.6 M in hexanes, 2.40 mmol) over 5 min, and the mixture was stirred for 1 h at the same temperature. Enyne 1a (170 mg, 1.00 mmol) was added and the mixture was allowed to warm gradually to 25 °C. After 3 h, CuCl (0.20 mmol, 0.018 g) and allyl chloride (0.325 mL, 4.00 mmol) were added and the mixture was left to stir at 25 °C for 12 h. The reaction mixture was quenched with 1 M HCl (10 mL) and extracted with EtOAc (3 × 20 mL). The combined organic phase was washed with sat. aq NaHCO3 (20 mL), H2O (2 × 20 mL), and brine (20 mL), and then dried over MgSO4, filtered, and concentrated under reduced pressure. Purification of the residue by column chromatography on silica gel (hexanes) gave the title compound. Yield: 224 mg (89%); colorless liquid; Rf  = 0.36 (hexanes). IR (KBr): 3072, 3052, 3019, 2977, 2950, 2929, 2863, 1643, 1595, 1494, 1440, 994, 908, 776, 701 cm–1. 1H NMR (600 MHz, CDCl3): δ = 7.30–7.28 (m, 2 H), 7.20–7.15 (m, 3 H), 5.92–5.85 (m, 1 H), 5.76–5.70 (m, 1 H), 5.08–4.90 (m, 4 H), 3.21–3.13 (m, 2 H), 2.81–2.77 (m, 1 H), 2.25–2.17 (m, 2 H), 2.12–2.05 (m, 2 H), 1.83–1.77 (m, 1 H), 1.70–1.63 (m, 2 H), 1.59–1.54 (m, 1 H), 1.51–1.41 (m, 2 H). 13C NMR (151 MHz, CDCl3): δ = 145.5, 143.5, 138.9, 136.6, 129.7, 128.5, 127.8, 125.9, 115.1, 114.5, 41.2, 39.0, 34.2, 32.0, 31.6, 31.2, 24.3. HRMS (TOF-MS-CI): m/z [M + H]+ calcd for C19H24: 252.1878; found: 252.1877.
  • 33 (6Z,9E)-9-Phenyl-2,3,3a,4,5,8-hexahydro-1H-cyclopenta[8]annulene (6a); Typical Example Compound 4a (0.39 mmol, 100 mg) was dissolved in CH2Cl2 (30 mL) and Ar gas was bubbled through the solution for 15 min. G II (0.019 mmol, 17 mg) was dissolved in CH2Cl2 (10 mL) and Ar gas was bubbled through the solution for 15 min. The solution of G II catalyst was transferred to the solution of 4a and the resulting mixture was stirred at reflux temperature for 2 h. The solvent was evaporated under reduced pressure under an Ar atm. Without purification, 1H NMR spectroscopic analysis of the residue [mesitylene (0.39 mmol) was used as an internal standard] indicated that compound 6a had formed in 99% yield. Purification of the residue by column chromatography on silica gel (hexanes) yielded the title compound. Yield: 57 mg (64%); yellow liquid; Rf  = 0.42 (hexanes). IR (KBr): 3075, 3055, 3022, 2947, 2929, 1595, 1497, 1449, 1437, 1072, 794, 737, 698 cm–1. 1H NMR (600 MHz, CDCl3): δ = 7.36–7.31 (m, 2 H), 7.25–7.20 (m, 3 H), 5.90–5.85 (m, 1 H), 5.67–5.63 (m, 1 H), 3.53–3.49 (m, 1 H), 3.15–3.12 (m, 1 H), 2.74 (q, J = 6.0 Hz, 1 H), 2.51–2.45 (m, 1 H), 2.43–2.37 (m, 1 H), 2.20–2.11 (m, 2 H), 2.06–2.01 (m, 1 H), 1.80–1.75 (m, 1 H), 1.68–1.63 (m, 1 H), 1.47–1.39 (m, 3 H). 13C NMR (151 MHz, CD2Cl2): δ = 145.0, 143.2, 134.3, 132.1, 130.1, 128.1, 128.0, 125.9, 43.9, 35.8, 35.3, 33.5, 33.3, 27.2, 25.1. HRMS (TOF-MS-CI): m/z [M + H]+ calcd for C17H20: 224.1565; found: 224.1564.

  • References and Notes

  • 1 Aubert C, Buisine O, Malacria M. Chem. Rev. 2002; 102: 813
    Search in Google Scholar
  • 4 Agnel G, Negishi E. J. Am. Chem. Soc. 1991; 113: 7424
    CrossrefSearch in Google Scholar
  • 5 Negishi E, Pour M, Cederbaum FE, Kotora M. Tetrahedron 1998; 54: 7057
    CrossrefSearch in Google Scholar
  • 6 Agnel G, Owczarczyk Z, Negishi E. Tetrahedron Lett. 1992; 33: 1543
    CrossrefSearch in Google Scholar
  • 7 Kemp MI, Whitby RJ, Coote SJ. Synthesis 1998; 552
    Thieme Connect
    • 8a Takahashi T, Aoyagi K, Hara R, Suzuki N. J. Chem. Soc., Chem. Commun. 1993; 1042
    • 8b Takahashi T, Aoyagi K, Kondakov DY. J. Chem. Soc., Chem. Commun. 1994; 747
    • 8c Aoyagi K, Hara R, Kondakov DY, Kasai K, Suzuki N, Takahashi T. Inorg. Chim. Acta 1994; 220: 319
      CrossrefSearch in Google Scholar
  • 11 Topolovčan N, Panov I, Kotora M. Eur. J. Org. Chem. 2015; 2868
  • 12 Takahashi T, Kotora M, Kasai K, Suzuki N. Tetrahedron Lett. 1994; 35: 5685
    CrossrefSearch in Google Scholar
  • 13 Kasai K, Kotora M, Suzuki N, Takahashi T. J. Chem. Soc., Chem. Commun. 1995; 109
  • 14 Takahashi T, Xi Z, Kotora M, Xi C. Tetrahedron Lett. 1996; 37: 7521
    CrossrefSearch in Google Scholar
  • 15 Lipshutz BH, Seki M. Tetrahedron 2005; 51: 4407
    Search in Google Scholar
  • 16 Liu Y, Xi C, Hara R, Nakajima K, Yamazaki A, Kotora M, Takahashi T. J. Org. Chem. 2000; 65: 6951
    CrossrefSearch in Google Scholar
  • 17 Kotora M, Umeda C, Ishida T, Takahashi T. Tetrahedron Lett. 1997; 38: 8355
    CrossrefSearch in Google Scholar
  • 18 Takahashi T, Kotora M, Kasai K, Suzuki N, Nakajima K. Organometallics 1994; 13: 4183
    CrossrefSearch in Google Scholar

      • For a review, see:
    • 20a Prunet J. Eur. J. Org. Chem. 2011; 3634-3647

      • For other typical examples, see:
    • 20b Michaut A, Miranda-García S, Menéndez JC, Coquerel Y, Rodriguez J. Eur. J. Org. Chem. 2008; 4988
    • 20c Dowling MS, Vanderwal CD. J. Org. Chem. 2010; 75: 6908
      CrossrefSearch in Google Scholar
  • 22 San Feliciano A, Barrero AF, Medarde M, Miguel del Corral JM, Aramburu A, Perales A, Fayos J. Tetrahedron Lett. 1985; 26: 2369
    CrossrefSearch in Google Scholar
  • 23 Mao S.-C, Gavagnin M, Mollo E, Guo Y.-W. Biochem. Syst. Ecol. 2011; 39: 408
    CrossrefSearch in Google Scholar
  • 24 Chen D, Chen W, Liu D, van Ofwegen L, Proksch P, Li W. J. Nat. Prod. 2013; 76: 1753
    CrossrefSearch in Google Scholar
  • 26 Urabe H, Suzuki K, Sato F. J. Am. Chem. Soc. 1997; 119: 10014
    CrossrefSearch in Google Scholar
  • 28 Scholl M, Ding S, Lee CW, Grubbs RH. Org. Lett. 1999; 1: 953
    Search in Google Scholar
  • 29 Kingsbury JS, Harrity JP. A, Bonitatebus PJ. Jr, Hoveyda AH. J. Am. Chem. Soc. 1999; 121: 791
    Search in Google Scholar
  • 31 As a result of the low polarity of the starting enyne, it was difficult to separate and purify product 4a from traces of the G I catalyst.
  • 32 (E)-{1-[2-(But-3-en-1-yl)cyclopentylidene]but-3-en-1-yl}benzene (4a); Typical Example To a solution of bis(cyclopentadienyl)zirconium dichloride (0.350 g, 1.20 mmol) in dry THF (7 mL) at –78 °C was added dropwise n-BuLi (1.50 mL, 1.6 M in hexanes, 2.40 mmol) over 5 min, and the mixture was stirred for 1 h at the same temperature. Enyne 1a (170 mg, 1.00 mmol) was added and the mixture was allowed to warm gradually to 25 °C. After 3 h, CuCl (0.20 mmol, 0.018 g) and allyl chloride (0.325 mL, 4.00 mmol) were added and the mixture was left to stir at 25 °C for 12 h. The reaction mixture was quenched with 1 M HCl (10 mL) and extracted with EtOAc (3 × 20 mL). The combined organic phase was washed with sat. aq NaHCO3 (20 mL), H2O (2 × 20 mL), and brine (20 mL), and then dried over MgSO4, filtered, and concentrated under reduced pressure. Purification of the residue by column chromatography on silica gel (hexanes) gave the title compound. Yield: 224 mg (89%); colorless liquid; Rf  = 0.36 (hexanes). IR (KBr): 3072, 3052, 3019, 2977, 2950, 2929, 2863, 1643, 1595, 1494, 1440, 994, 908, 776, 701 cm–1. 1H NMR (600 MHz, CDCl3): δ = 7.30–7.28 (m, 2 H), 7.20–7.15 (m, 3 H), 5.92–5.85 (m, 1 H), 5.76–5.70 (m, 1 H), 5.08–4.90 (m, 4 H), 3.21–3.13 (m, 2 H), 2.81–2.77 (m, 1 H), 2.25–2.17 (m, 2 H), 2.12–2.05 (m, 2 H), 1.83–1.77 (m, 1 H), 1.70–1.63 (m, 2 H), 1.59–1.54 (m, 1 H), 1.51–1.41 (m, 2 H). 13C NMR (151 MHz, CDCl3): δ = 145.5, 143.5, 138.9, 136.6, 129.7, 128.5, 127.8, 125.9, 115.1, 114.5, 41.2, 39.0, 34.2, 32.0, 31.6, 31.2, 24.3. HRMS (TOF-MS-CI): m/z [M + H]+ calcd for C19H24: 252.1878; found: 252.1877.
  • 33 (6Z,9E)-9-Phenyl-2,3,3a,4,5,8-hexahydro-1H-cyclopenta[8]annulene (6a); Typical Example Compound 4a (0.39 mmol, 100 mg) was dissolved in CH2Cl2 (30 mL) and Ar gas was bubbled through the solution for 15 min. G II (0.019 mmol, 17 mg) was dissolved in CH2Cl2 (10 mL) and Ar gas was bubbled through the solution for 15 min. The solution of G II catalyst was transferred to the solution of 4a and the resulting mixture was stirred at reflux temperature for 2 h. The solvent was evaporated under reduced pressure under an Ar atm. Without purification, 1H NMR spectroscopic analysis of the residue [mesitylene (0.39 mmol) was used as an internal standard] indicated that compound 6a had formed in 99% yield. Purification of the residue by column chromatography on silica gel (hexanes) yielded the title compound. Yield: 57 mg (64%); yellow liquid; Rf  = 0.42 (hexanes). IR (KBr): 3075, 3055, 3022, 2947, 2929, 1595, 1497, 1449, 1437, 1072, 794, 737, 698 cm–1. 1H NMR (600 MHz, CDCl3): δ = 7.36–7.31 (m, 2 H), 7.25–7.20 (m, 3 H), 5.90–5.85 (m, 1 H), 5.67–5.63 (m, 1 H), 3.53–3.49 (m, 1 H), 3.15–3.12 (m, 1 H), 2.74 (q, J = 6.0 Hz, 1 H), 2.51–2.45 (m, 1 H), 2.43–2.37 (m, 1 H), 2.20–2.11 (m, 2 H), 2.06–2.01 (m, 1 H), 1.80–1.75 (m, 1 H), 1.68–1.63 (m, 1 H), 1.47–1.39 (m, 3 H). 13C NMR (151 MHz, CD2Cl2): δ = 145.0, 143.2, 134.3, 132.1, 130.1, 128.1, 128.0, 125.9, 43.9, 35.8, 35.3, 33.5, 33.3, 27.2, 25.1. HRMS (TOF-MS-CI): m/z [M + H]+ calcd for C17H20: 224.1565; found: 224.1564.

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Scheme 1 Retrosynthetic analysis for the formation of a [6.3.0]bicycloundecane framework
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Figure 1 Examples of natural products containing an eight-membered-ring framework
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Scheme 2 Bisallylation of zirconacyclopentenes 2 with allyl chloride
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Scheme 3 Ring-closing metathesis of 1,9-decadienes 4 to give cyclooctadienes 6; Grubbs 2nd generation (G II) catalyst unless otherwise mentioned. 1H NMR yields are in parentheses. a Obtained as complex mixture; the yield was not determined. b nr = no reaction.
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Scheme 4 Synthesis of 1,9-decadiene 8 and its ring-closing metathesis to give 9