9534
J. Org. Chem. 1996, 61, 9534-9537
Zeolite-Mediated Cyclization of an Epoxide-Containing Polyene† Stephanie E. Sen,* Yan zhi Zhang, and Steven L. Roach Department of Chemistry, Indiana University-Purdue University at Indianapolis (IUPUI), 402 North Blackford Street, Indianapolis, Indiana 46202 Received April 22, 1996 (Revised Manuscript Received October 16, 1996X)
The utility of zeolites as promoters for the cyclization of an epoxide-containing polyene has been investigated. Reaction of polyene 1 with oven-dried 4 Å molecular sieves (type A zeolite) proceeds efficiently to generate bicyclic alcohol 2 in a 90% isolated yield. The reaction is sensitive to a variety of factors, including solvent type, water content, and zeolite acidity. Reactivity is apparently due to the zeolite lattice, since alumina and silica either are unreactive or generate a complex mixture of epoxide ring-opened products. Compared to the aluminum-based Lewis acid Me2AlCl, the zeolitepromoted cyclization of 1 was a more facile reaction, providing excellent product recovery after filtration. These results indicate that zeolites represent a new class of promoters in biomimetic polyene cyclizations. Introduction
Scheme 1
Biomimetic polyene cyclization represents an important method for the preparation of polycycles with controlled stereochemistry. While substantial progress has been made with the introduction of acetal and allylic alcohol functionalities as initiating groups in these cyclization reactions,1 few successful applications of the epoxide functionality, the normal initiator for many naturally-occurring cyclases, have been demonstrated.2 Unfortunately, known methodology for the cyclization of epoxide-containing polyenes using aluminum- and titanium-based Lewis acids3 can result in low yields and the production of both partially cyclized and rearranged byproducts. Because of the importance of epoxides in biological cyclizations4 and their synthetic utility in generating lanostane-type A ring systems, the development of new promoters for the biomimetic cyclization of epoxide-containing polyenes continues to be an active area of research. The utility of zeolites as selective adsorbents and as cracking catalysts in the petroleum industry has been known for many years.5,6 However, zeolites have also been examined as catalysts for other synthetic transformations.7 Examples of zeolite-promoted reactions include Friedel-Crafts alkylation and acylation,8,9 aldol condensations,10 photochemical and acid-catalyzed cyclizations,11,12 and ring-opening reactions.13 Modification of
the zeolite either by the introduction of reactive metal centers or by reagent “doping” has expanded the range of reactions now available with this porous material.14 Because of the known properties of zeolites as superacids and as cavity-selective catalysts, we became interested in determining the utility of these materials in generating polycycles by polyene cyclization methodology. Herein, we report our initial results involving the zeoliteinduced bicyclization of polyene 1, which possesses an epoxide initiator and a silicon (propargylic silane) terminator (Scheme 1). Cyclizations of this polyene using (i-PrO)TiCl3 and Me2AlCl were also examined so that a comparison between traditional Lewis acid promoters and zeolite methodology could be made. Reaction of polyene 1 with oven-dried 4 Å molecular sieves in refluxing CHCl3 for 40 min results in conversion of starting material to bicyclic product 2. As described below, the reaction requires the proper balance between solvent type, water content, and zeolite acidity. Results and Discussion
†
This paper is dedicated to the memory of William S. Johnson. Abstract published in Advance ACS Abstracts, November 15, 1996. (1) Johnson, W. S. Tetrahedron 1991, 47, xi. (2) (a) Taylor, S. K. Org. Prep. Proc. Int. 1992, 24, 245. (b) Corey, E. J.; Lee, J. J. Am. Chem. Soc. 1993, 115, 8873. (c) Corey, E. J.; Lin, S. J. Am. Chem. Soc. 1996, 118, 8765. (3) (a) Fish, P. V.; Johnson, W. S. J. Org. Chem. 1994, 59, 2324. (b) Mori, K.; Aki, S.; Kido, M. Liebigs Ann. Chem. 1994, 319. (c) Corey, E. J.; Sodeoka, M. Tetrahedron Lett. 1991, 32, 7005. (d) Yee, N. K. N.; Coates, R. M. J. Org. Chem. 1992, 57, 4598. (e) Aziz M.; Rouessac, F. Tetrahedron 1988, 44, 101. (f) Armstrong, R. J.; Weiler, L. Can. J. Chem. 1983, 61, 214. (4) Abe, I.; Rohmer, M.; Prestwich G. D. Chem. Rev. 1993, 93, 2189. (5) Ho¨lderich, W.; Hesse, M.; Na¨umann, F. Angew. Chem., Int. Ed. Engl. 1988, 27, 226. (6) For a recent article on regioselective hydrocarbon isomerization, see: Martens, J. A.; Souverijns, W.; Verrelst, W.; Parton, R.; Froment, G. F.; Jacobs, P. A. Angew. Chem., Int. Ed. Engl. 1995, 34, 2528. (7) Dartt, C. B.; Davis, M. E. Catal. Today 1994, 19, 151. (8) (a) Sugi, Y.; Toba, M. Catal. Today 1994, 19, 187. (b) Gunnewegh, E. A.; Hoefnagel, A. J.; van Bekkum, H. J. Mol. Catal. 1995, 100, 87. (9) (a) Chiche, B.; Finiels, A.; Gauthier, C.; Geneste, P. J. Org. Chem. 1986, 51, 2128. (b) Singh, A. P.; Bhattacharya, D.; Sharma, S. J. Mol. Catal. 1995, 102, 139. (c) Gunnewegh, E. A.; Gopie, S. S.; van Bekkum, H. J. Mol. Catal. 1996, 106, 151. X
S0022-3263(96)00745-1 CCC: $12.00
Polyene 1 was synthesized in seven steps (37% overall yield) from 3-chloropropionaldehyde diethyl acetal using the procedures developed by Johnson and co-workers for the construction of larger polyene skeletons (Scheme 2).15 The final step of the reaction sequence, formation of the (10) (a) Xu, T.; Munson, E. J.; Haw, J. F. J. Am. Chem. Soc. 1994, 116, 1962. (b) Climent, M. J.; Corma, A.; Iborra, S.; Primo, J. J. Catal. 1995, 151, 60. (11) Ramamurthy, V.; Sanderson, D. R. Tetrahedron Lett. 1992, 33, 2757. (12) (a) Sreekumar, R.; Narayana Murthy, Y. V. S.; Narayana Pillai, C. J. Chem. Soc., Chem. Commun. 1992, 1624. (b) Stamm, T.; Kouwenhoven, H. W.; Seebach, D.; Prins, R. J. Catal. 1995, 155, 268. (13) (a) Takeuchi, H.; Kitajima, K.; Yamamoto, Y.; Mizuno, K. J. Chem. Soc., Perkin Trans. 2 1993, 199. (b) Onaka, M.; Sugita, K.; Izumi, Y. J. Org. Chem. 1989, 54, 1116. (14) (a) Martin-Luengo, M. A.; Yates, M. J. Mater. Sci. 1995, 30, 4483. (b) Kumar, P.; Kumar, R.; Pandey, B. SynLett 1995, 289. (c) Sheldon, R. A. J. Mol. Catal. 1996, 107, 75. (15) Johnson, W. S.; Yarnell, T. M.; Myers, R. F.; Morton, D. R.; Boots, S. G. J. Org. Chem. 1980, 45, 1254.
© 1996 American Chemical Society
Zeolite-Mediated Polyene Cyclization Scheme 2. Synthesis of Polyene 1a
J. Org. Chem., Vol. 61, No. 26, 1996 9535 Table 1. Effect of Different Solvents on the Cyclization of Polyene 1a recovered materials (%)b
reaction conditions
a
Conditions: (a) Li acetylide‚EDA, DMSO (79%); (b) n-BuLi, then Me3SiCH2I (99%); (c) PPTS, acetone/H2O (quantitative); (d) CH2dC(CH3)MgBr, THF (85%); (e) CH3C(OEt)3, propionic acid (74%); (f) DIBALH, THF, -94 °C (97%); (g) (CH3)2CHSPh2BF4, t-BuLi, THF, -78 °C (78%).
gem-dimethyl epoxide from aldehyde 3, was troublesome due to the instability of diphenylsulfonium isopropylide. Reactions with the sulfur ylide required the rigorous exclusion of both air and moisture and, because of its thermal instability were typically conducted between -78 and -60 °C. Under these conditions, epoxide 1 was formed in 75-80% isolated yield. Diphenylsulfonium isopropylide was generated from diphenylisopropylsulfonium tetrafluoroborate, prepared by the method of Julia and co-workers, involving triflic acid-induced addition of phenyl sulfide to 2-propanol, followed by anion exchange with tetrafluoroboric acid.16 Although the alternative condensation of phenyl sulfide with 2-iodopropane in the presence of silver tetrafluoroborate17 provided higher reaction yields (45-55% compared to 10-25%), the resulting salt contained unidentified contaminants that led to difficulties in epoxide isolation. To determine optimal conditions for the cyclization of polyene 1, small-scale reactions (2-5 mg) were performed. Several potential factors responsible for zeolite reactivity were explored, and the results of these experiments are summarized below. Solvent Effects. Results from the cyclization of 1 with 4 Å molecular sieves (type A zeolite, Na form) using several different solvents are presented in Table 1. The cyclization of polyene 1 occurred in a variety of nonpolar and halogenated solvents but was significantly inhibited when coordinating solvents were used. Although temperature had an important effect on reaction rate (toluene at rt versus reflux), the use of lower-boiling halogenated solvents increased both the rate and the selectivity of the reaction. Thus, cyclization of polyene 1 using toluene as solvent (at reflux) occurred within 5 h to provide 2 and a mixture of epoxide ring-opened and partially cyclized materials, while reaction of 1 in refluxing CHCl3 required only 40 min for complete consumption of starting material to yield bicycle 2 as the sole reaction product. The inhibitory effects of both THF and CH3CN suggest that these solvents compete with the reactant for coordinating sites on the zeolite,18 thus impeding cyclization chemistry. Water Content. A qualitative examination of differing amounts of water present within the zeolite was undertaken to determine its effect on the cyclization of epoxide-containing polyene 1. A sample of 4 Å molecular (16) Badet, B.; Julia, M. Tetrahedron Lett. 1979, 13, 1101. (17) (a) The Chemistry of the Sulfonium Group; Stirling, C. J. M., Patai, S., Eds.; John Wiley & Sons: New York, 1981. (b) Corey, E. J.; Jautelat, M.; Oppolzer, W. Tetrahedron Lett. 1967, 24, 2325. (18) Corma, A.; Esteve, P.; Martı´nez, A. J. Catal. 1996, 161, 11.
solvent
temp (°C)
time
bicycles 2 (4)
polyene 1
toluene toluene benzene CH3CN THF hexane CCl4 CH2Cl2 CHCl3i
25 110 80 82 66 68 76 40 61
2 days 5h 5h 4h 4.5 h 4.5 h 3.5 h 3.5 h 40 min
0 43 (6) 65 6 0 60 (18) 64 (5) 100 (0) 100 (0)
92c 0d 0e 79f 100 0g 18h 0 0
a Reaction conditions: 2 mg of polyene 1 and 30 mg of ovendried, crushed 4 Å molecular sieves in 5 mL of solvent, at reflux. b GC yield of isolated reaction mixture. c Byproduct composition: 5% 5 and 3% 6. d Byproduct composition: 9% 7, 16% 5, 6% 6, remainder (
