Catalytic one-pot synthesis of [5.5.5.6]fenestrane systems via a dicobalt octacarbonyl-catalyzed tandem cycloaddition of dienediynes

Abstract

Catalytic one-pot synthesis of fenestrane derivatives from dienediynes was developed: fenestranes were synthesized in high yields by a dicobalt octacarbonyl-catalyzed tandem cycloaddition of dienediynes.

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One of the challenging uses of organometallic chemistry is to find reactions and strategies that allow for the facile conversion of simple compounds into complex materials, medicines, or molecules of theoretical interest.¹ Recently we have demonstrated² that the dicobalt octacarbonyl-catalyzed carbonylative cycloaddition of diene or triyne with/without diene or alkyne can produce up to four new 5-membered rings in one step. This success encouraged us to analyze the retrosynthesis of fenestranes,³ which has been studied in relation to the question of whether a tetrahedral carbon can be flattened.

Most of the previous syntheses of fenestranes are based on the Pauson-Khand reaction,⁴ photocycloaddition,⁵ Pd-catalyzed carbonylative cyclization,⁶ aldolization⁷ or cyclodehydration⁸ as the key step(s). They gave only small quantities of the desired tetracycles and suffered from a low selectivity and tedious separating problems. Now we report a catalytic synthesis of fenestrane derivatives using dicobalt octacarbonyl-catalyzed tandem cycloaddition of dienediynes under CO pressure.

Keese’s group reported a one-pot synthesis of [5.5.5.5]fenestranes from enediyne via the Pauson-Khand reaction.^4b However, the reported yields were low.

Thus, at first we thought that enediyne (1) or triynes (2) might be appropriate precursors for the construction of a fenestrane structure through two sequential [2 + 2 + 1] cycloaddition reactions. The inner triple bond of triynes might permit the construction of a quaternary center from two sequential carbon–carbon bond formation steps. Contrary to our expectation, a fenestrane structure was not formed. Instead, in the case of enediynes, polymeric materials were obtained and, in the case of triynes, an unnatural tetracyclic structure was obtained as the sole product.⁹

After many experimental trials, we chose dienediyne as a precursor to fenestrane.

For the cyclization, dienediyne derivatives 1a, 1b, and 1c (Scheme 1) were prepared from the α-hydroxy diynes 2a, 2b and 2c. Compound 2b was prepared according to the procedures in the literature.¹⁰ The same procedure as used for the synthesis of 2b has been applied to the synthesis of 2a and 2c. The reaction of α-hydroxy diynes with sodium hydride followed by hexa-2,4-dienyl bromide led to the isolation of 1a, 1b, and 1c in high yields which were fully characterized.¹¹‡

Scheme 1

Treatment of dienediyne 1a (0.68 mmol) with dicobalt octacarbonyl (5 mol%) in dichloromethane at 130 °C under 30 atm of CO for 18 h yielded a fenestrane derivative 3a in 84% yield [eqn. (1)].§

The structure of 3a was established by ¹H and ¹³C NMR spectroscopic investigations (COSY, long range COSY, DEPT, HECTOR, long range HECTOR, phase sensitive NOESY, and 2D-INADEQUATE), and mass spectrometry.¶ The correlation peaks obtained from the COSY spectrum allow us to identify the consecutive connections of methyl-14 protons to methyine-9 proton, 9 to 10, 10 to 11, 11 to 12 and 12 to 13. The other connections were derived from the combinative information observed from the DEPT, 2D C–H correlation, and 2D long range C–H correlation spectra. No other products were observed. The reaction involves the formation of five carbon–carbon bonds.

Although this multibond formation reaction seems to be complex, it may be simple: the dicobalt octacarbonyl-catalyzed carbonylative [2 + 2 + 1] cycloaddition of diyne with carbon monoxide followed by a subsequent intramolecular [4 + 2] cycloaddition provides 3a. Another feasible reaction pathway is that the diene unit reacts first with the closer triple bond and the thus formed cyclohexa-1,4-diene undergoes a Pauson-Khand reaction with the remote triple bond.¹² The central triple bond acts as a double functionality that could be used in both cyclizations. In the same way as in the synthesis of 3a, the dicobalt octacarbonyl-catalyzed tandem cyclization of diendiynes 1b and 1c afforded 3b and 3c in 74% and 51% yields, respectively.

In conclusion, we have developed a new catalytic route to fenestrane derivatives via dicobalt octacarbonyl-catalyzed cycloaddition of dienediynes. The following significant points are noteworthy. All the reactions described here are catalytic with high conversion rates and experimentally a simple reaction, a one-pot reaction.

This work was supported by grant No. 2000-2-12200-001-1 from the Basic Research Program of the Korea Science and Engineering Foundation (KOSEF), KOSEF (1999-1-122-001-5), and KOSEF through the Center for Molecular Catalysis. SUS and DHK thank the Ministry of Education for the Brain Korea 21 Fellowship.

Notes and references

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3. Reviews on fenestrane chemistry: (a) D. Kuck, in Advances in Theoretically Interesting Molecules, ed. R. P. Thummel, JAI Press, Greenwich, CT, 1998, vol. 4, p. 81; ; (b) M. Thommen and R. Keese, Synlett, 1997, 231; (c) W. Luef and R. Keese, in Advances in Strain in Organic Chemistry, ed. B. Halton, JAI Press, Greenwich, CT, 1993, vol. 3, p. 229;; (d) W. C. Agosta, in The Chemistry of Alkanes and Cycloalkanes, ed. S. Patai and Z. Rappoport, Wiley, New York, 1992, p. 927;; (e) A. K. Gupta, X. Fu, J. P. Snyder and J. M. Cook, Tetrahedron, 1991, 47, 3665; (f) K. Krohn, in Organic Synthesis Highlights, ed. J. Mulzer, H.-J. Altenbach, M. Braun, K. Krohn and H.-U. Reissig, VCH, Weinheim, 1991, p. 121;; (g) B. R. Venepalli and W. C. Agosta, Chem. Rev., 1987, 87, 399; (h) R. Keese, in Organic Synthesis; Modern Trends, ed. O. Chizhov, Blackwell, Oxford, 1987, p. 43..
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11. See the Supporting Information.†.
12. A referee suggested this reaction pathway. The authors thank the referee for this suggestion..

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Footnotes

† Electronic supplementary information (ESI) available: characterization of synthesized compounds. See http://www.rsc.org/suppdata/cc/b1/b108034b/

‡ Compound 2a (0.20 g, 0.69 mmol) was dissolved in 15 ml of THF. The solution was cooled to 0 °C. To the solution was added NaH (40 mg, 50 wt% in oil). After the solution was stirred for 1 h, hexa-2,4-dienyl bromide (0.17 g, 1.05 mmol) was added to the solution. The resulting solution was stirred for 12 h and was quenched with diethyl ether and sat. NH₄Cl solution. The ether layer was separated, dried over anhydrous MgSO₄, concentrated and the residue separated on a silica gel eluting with hexane and diethyl ether (v/v, 10:1). Yield: 0.23 g (89%). 1a: ¹H NMR (CDCl₃, 300 MHz): δ 7.39 (m, 4 H), 7.28 (m, 6 H), 6.27 (dd, 15.0, 10.0 Hz, 1 H), 6.00 (dd, 15.0, 10.0 Hz, 1 H), 5.70 (m, 2 H), 4.37 (dd, 13.0, 5.4 Hz, 1 H), 4.26 (s, 1 H), 4.08 (dd, 13.0, 7.2 Hz, 1 H), 2.65 (d, 17.0 Hz, 1 H), 2.47 (d, 17.0 Hz, 1 H), 1.71 (d, 6.2 Hz, 3 H), 1.20 (s, 3 H), 1.19 (s, 3 H) ppm; ¹³C NMR (CDCl₃, 75 MHz): δ133.6, 131.7, 131.6, 130.9, 129.8, 128.2, 128.1, 127.5, 126.7, 124.1, 122.9, 87.9, 86.9, 82.6, 75.4, 69.7, 39.1, 29.4, 23.7, 22.8, 18.0 ppm; exact mass calc. 368.2140, obsd. 368.2137.

§ Compound 1a (0.25 g, 0.68 mmol), 15 ml of CH₂Cl₂, and Co₂(CO)₈ (12 mg, 0.035 mmol) were put in a high pressure reactor (100 ml). After the solution was bubbled with nitrogen for 1 min, the reactor was pressurized with 30 atm of CO. The reactor was heated at 130 °C for 18 h. After the reactor was cooled to rt, excess gas was released and the reaction mixture was transferred into a one-neck flask (50 ml). Removal of the solvent followed by chromatography on a silica gel column eluting with hexane and diethyl ether (v/v, 5∶1) gave 3a in 84% yield (0.23 g, 0.58 mmol).

¶ ¹H NMR (CDCl₃, 300 MHz): δ 7.60–7.24(m, 10 H), 6.04 (m, 1 H), 5.73 (m, 1 H), 4.16 (dd, 8.7, 5.5 Hz, 1 H), 3.84 (dd, 8.7, 5.5 Hz, 1 H), 3.70 (s, 1 H), 2.90 (m, 1 H), 2.72 (m, 1 H), 2.68 (d, 15.0 Hz, 1 H), 2.43 (d, 15.0 Hz, 1 H), 1.22 (d, 7.3 Hz, 3 H), 1.04 (s, 3 H), 0.00 (s, 3 H) ppm; ¹³C NMR (CDCl₃, 75 MHz): δ 209.2, 180.7, 139.2, 137.9, 134.8, 131.3, 129.8, 128.9, 128.3, 127.7, 126.6, 89.6, 75.3, 70.3, 65.9, 48.0, 43.9, 42.7, 36.8, 25.9, 23.3, 18.9 ppm; IR νCO 1693 cm⁻¹; exact mass calc. 396.2089, obsd. 396.2088.

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