Published on Web 10/23/2003
Stereoselective Palladium-Catalyzed Carbocyclization of Allenic Allylic Carboxylates Johan Franze´ n, Joakim Lo¨fstedt, Jennica Falk, and Jan-E. Ba¨ckvall* Contribution from the Department of Organic Chemistry, Arrhenius Laboratory, Stockholm UniVersity, SE-106 91 Stockholm, Sweden Received July 19, 2003; E-mail:
[email protected] Abstract: Palladium(0)-catalyzed reaction of allene-substituted allylic carboxylates 3-8 employing 2-5 mol % of Pd(dba)2 in refluxing toluene leads to the carbocyclization and elimination of carboxylic acid to give bicyclo[4.3.0]nonadiene and bicyclo[5.3.0]decadiene derivatives (12-17). The carbon-carbon bond formation is stereospecific, occurring syn with respect to the leaving group. Addition of maleic anhydride as a ligand to the above-mentioned procedures changed the outcome of the reaction, and under these conditions 3-5 afforded cycloisomerized products 21-23. The experimental results are consistent with a mechanism involving oxidative addition of the allylic carboxylate to Pd(0) to give an electron-deficient (πallyl)palladium intermediate, followed by nucleophilic attack by the allene on the face of the π-allyl opposite to that of the palladium atom. Furthermore, it was found that the Pd(dba)2-catalyzed cyclization of the trans-cycloheptene derivative (trans-8) can be directed to give either the trans-fused (trans-17) or the cisfused (cis-17) ring system by altering the solvent. The former reaction proceeds via a nucleophilic transallene attack on the (π-allyl)palladium intermediate, whereas the latter involves a syn-allene insertion into the allyl-Pd bond of the same intermediate. The products from the carbocylization undergo stereoselective Diels-Alder reactions to give stereodefined polycyclic systems in high yields.
Introduction
Intramolecular nucleophilic addition to (π-allyl)palladium intermediates offers a powerful methodology for the construction of a great variety of cyclic compounds under mild reaction conditions.1,2 Some significant features that these types of reactions display are the high control of regio- and stereoselectivity. In catalytic reactions, the intermediate (π-allyl)palladium complex can be generated from an allylic carboxylate,3,4 a conjugated diene,5,6 or an allene.7,8 Intramolecular attack by heteroatom nucleophiles or a stabilized carbon anion on the π-allyl results in heterocyclic and carbocyclic products.1,9 (1) Trost, B. M. Angew. Chem., Int. Ed. Engl. 1989, 28, 1173. (2) (a) Tsuji, J. Palladium Reagents and Catalysis: InnoVations in Organic Synthesis; Wiley: Chichester, 1995. (b) Tsuji, J. Transition Metal Reagents and Catalysts - InnoVation in Organic Synthesis; Wiley: New York, 2000. (3) (a) Trost, B. M. Acc. Chem. Res. 1980, 13, 385. (b) Godleski, S. A. In ComprehensiVe organic synthesis; Trost, B. M., Flemming, I., Semmelhack, M. F., Eds.; Pergamon: Oxford, 1991; Vol. 4, Chapter 3.3. (4) (a) Takacs, J. M.; Lawson, E. C.; Clement, F. J. Am. Chem. Soc. 1997, 119, 5956. (b) Me´ndez, M.; Cuerva, J. M.; Gomez-Bengoa, E.; Ca´rdenas, D. J.; Echavarren, A. M. Chem.-Eur. J. 2002, 8, 3620. (5) Ba¨ckvall, J. E. In Metal-catalyzed Cross-Coupling Reactions; Stang, P., Diederich, F., Eds.; Wiley-VCH: Weinham, 1998; pp 339-385. (6) (a) Nystro¨m, J. E.; Nordberg, R. E.; Ba¨ckvall, J. E. J. Am. Chem. Soc. 1985, 107, 3676. (b) Ba¨ckvall, J. E.; Andersson, P. G. J. Am. Chem. Soc. 1992, 114, 6374. (7) (a) Zimmer, R.; Dinesh, C. U.; Nandanam, E.; Khan, F. A. Chem. ReV. 2000, 100, 3067. (b) Cazes, B. Pure Appl. Chem. 1990, 62, 1867. (c) Gamez, P.; Arriente, C.; Gore´, J.; Casez, B. Tetrahedron 1998, 54, 14835. (d) Yamamoto, Y.; Radhakrishnan, U. Chem. Soc. ReV. 1999, 28, 199. (e) Trost, B. M.; Gerusz, V. J. J. Am. Chem. Soc. 1995, 117, 5156. (8) (a) Jonasson, C.; Horva´th, A.; Ba¨ckvall, J. E. J. Am. Chem. Soc. 2000, 122, 9600. (b) Jonasson, C.; Karstens, W. F. J.; Hiemstra, H.; Ba¨ckvall, J.-E. Tetrahedron Lett. 2000, 41, 1619. (c) Bates, R. W.; Satcharoen, V. Chem. Soc. ReV. 2002, 31, 12. (9) Heumann, A.; Re´glier, M. Tetrahedron 1995, 51, 975. 14140
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However, a major limitation of carbocyclization reactions is that the nucleophilic carbon partner in most cases is restricted to stabilized nucleophiles. Unactivated carbon-carbon multiple bonds, that is, π-nucleophiles, are attractive carbon “nucleophiles” for (π-allyl)palladium intermediates due to their broad functional group tolerance and easy accessibility.10 After investigation of this concept, we were able to report on the first established example of trans-attack by an allenic double bond on a (π-allyl)palladium complex.11 This concept was further developed to involve transallene attack on a (π-diene)palladium complex.12 Such a transattack by a π-nucleophile on π-coordinated palladium ligand is rare,13 and one of the few previously established examples is (10) Attack by an unactivated carbon-carbon double bond on a (π-allyl)palladium complex has been inferred as a mechanistic possibility in catalytic carbon-carbon bond forming reactions, but so far no stereochemical evidence has been provided. (a) Oppolzer, W. Angew. Chem., Int. Ed. Engl. 1989, 28, 38. (b) Oppolzer, W.; Gaudin, J. M.; Birkinshaw, T. N. Tetrahedron Lett. 1988, 29, 4705. (c) Aubert, C.; Buisine, O.; Malacria, M. Chem. ReV. 2002, 102, 813. (d) Trost, B. M.; Luengo, J. I. J. Am. Chem. Soc. 1988, 110, 8239. (11) Franze´n, J.; Lo¨fstedt, J.; Dorange, I.; Ba¨ckvall, J. E. J. Am. Chem. Soc. 2002, 124, 11246. (12) Dorange, I.; Lo¨fstedt, J.; Na¨rhi, K.; Franze´n, J.; Ba¨ckvall, J. E. Chem.Eur. J. 2003, 9, 3445. (13) (a) In general, the use of unactivated double bonds as nucleophiles in organometallic chemistry is rare but has been proposed in palladiumcatalyzed Cope rearrangment,13b in platinum-catalyzed intramolecular reactions of enynes,13c-e and in platinum-catalyzed dimerization of olefins13f as likely pathways. (b) Overman, L. E.; Jacobsen, E. J. J. Am. Chem. Soc. 1982, 104, 7225. (c) Mendez, M.; Mun˜os, Nevado, C.; Ca´rdenas, D. J.; Echavarren, A. M. J. Am. Chem. Soc. 2001, 123, 10511. (d) Me´ndez, M.; Echavarren, A. M. Eur. J. Org. Chem. 2002, 67, 15. (e) Oi, S.; Tsukamoto, I.; Miyano, S.; Inoue, Y. Organometallics 2001, 20, 3704. (f) Hahn, C.; Cucciolito, M. E.; Vitagliano, A. J. Am. Chem. Soc. 2002, 124, 9038. 10.1021/ja037398u CCC: $25.00 © 2003 American Chemical Society
Carbocyclization of Allenic Allylic Carboxylates
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Scheme 1
Scheme 2
the use of an allylsilane as a nucleophile on (π-allyl)palladium and (π-diene)palladium complexes.14 During the past decade, palladium-catalyzed reactions of allenes have attracted considerable interest.7,8,15,16 We have recently reported on the intramolecular palladium(II)-catalyzed carbocyclizations of allene substituted 1,3-dienes.16 In the present paper, we have studied the synthetic applications, scope, and limitations of the palladium(0)-catalyzed reaction of allenes with allylic carboxylates. We have found that oxidative addition of a palladium(0) catalyst to allylic carboxylates A leads to a (π-allyl)palladium intermediate, which is attacked by the allene on the coordinated allyl group in an intramolecular reaction with carbon-carbon bond formation. The cyclized products B were obtained in good yields (Scheme 1). Under these reaction conditions, the new carbon-carbon bond is stereospecifically formed with syn stereochemistry with respect to the allylic carboxylate. Thus, for the catalytic cyclization of the sevenmembered rings of type A, the cis-substrate gave the cis-fused product, whereas the trans-substrate afforded the trans-fused product. It was also demonstrated that the reaction path can be altered from trans-allene attack to the more commonly observed syn-allene insertion17 by changing the ligand/solvent system. In this way, catalytic cyclization of the trans seven-membered (14) Allylsilanes have been proven to act as nucleophiles on (π-diene)- and (π-allyl)palladium complex: (a) see ref 13d. (b) Castan˜o, A. M.; Persson, B. A.; Ba¨ckvall, J. E. Chem.-Eur. J. 1997, 3, 482. (c) Trost, B. M.; Keinan, E. Tetrahedron Lett. 1980, 21, 2595. (15) Ma, S.; Zhan, J.; Lu, L. Chem.-Eur. J. 2003, 9, 2447. (16) Lo¨fstedt, J.; Franze´n, J.; Ba¨ckvall, J. E. J. Org. Chem. 2001, 66, 8015. (17) It has been shown in previous studies that the carbon-carbon multiple bond, for example, olefins,17a-c dienes,17d and allenes,17e,f can inset into (π-allyl)palladium bonds. (a) See ref 10a,b. (b) Ca´rdenas, D. J.; Alcamı´, M.; Cossı´o, F.; Me´ndez, M.; Echavarren, A. M. Chem.-Eur. J. 2003, 9, 96. (c) Go´mez-Bengoa, E.; Cuerva, J. M.; Echavarren, A. M.; Martorell, G. Angew. Chem., Int. Ed. Engl. 1997, 36, 767. (d) Trost, B. M.; Luengo, J. I. J. Am. Chem. Soc. 1988, 110, 8239. (e) Stoichiometric reactions, see: Hughes, R. P.; Powell, J. J. Organomet. Chem. 1969, 20, P17; 1973, 60, 409. (f) Catalytic reactions, see: Doi, T.; Yanagisawa, A.; Nakanishi, S.; Yamamoto, K.; Takahashi, T. J. Org. Chem. 1996, 61, 2602.
ring substrate could be directed to give either the trans- or the cis-fused product by simply altering the solvent. It was also possible to change the course of the reaction to favor the cycloisomerized product C, by adding maleic anhydride to the Pd(dba)2 reaction mixture (Scheme 1). Results and Discussion
The substrates chosen for this study were readily available via the palladium(II)-catalyzed cis-1,4-chloroacyloxylation of the corresponding 1,3-diene to give cis-1 (Scheme 2).18 Subsequent substitution of the chloride with either retention (Pd0) or inversion (heat) afforded cis- and trans-allylic malonates 2, respectively.19 A coupling of the latter products with 1-bromo3,3-dimethylallene20 yielded, in each case, the required substrates cis- and trans-3 in good to moderate yields (for further details, see Supporting Information).21 Intramolecular Palladium(0)-Catalyzed Allylations of Allenes. The palladium(0)-catalyzed reaction of cis-3a resulted in a carbocyclization to produce cis-12. The reaction conditions were varied (Table 1), and it was found that the use of 2 mol % of Pd(dba)2 in refluxing toluene gave the best result. Under these conditions, cis-12 was obtained in 76% isolated yield after 2 h of reaction time (Table 1, entry 7). If the temperature or catalyst load was lowered, the reaction time increased. Refluxing (18) Ba¨ckvall, J. E.; Granberg, K. L.; Hopkins, R. B. Acta Chem. Scand. 1990, 44, 492. (19) Ba¨ckvall, J. E.; Nystro¨m, J. E.; Nordberg, R. E. J. Am. Chem. Soc. 1985, 107, 3676. (20) Sigman, S. S.; Eaton, B. E. J. Am. Chem. Soc. 1996, 118, 11783. (21) To succeed in the coupling reaction of bromoallene with the acetate and benzoate analogues 2, it was essential that the sodium hydride (60% dispersion in mineral oil) was of good quality. Sodium hydride that has been exposed to air moisture can contain substantial amounts of sodium hydroxide, which leads to degradation of the acetate and benzoate analogues 2 most likely via hydrolysis of the ester functions under the reaction condition used (see Scheme 2). However, the pivalic analogues of 2 were not sensitive to the quality of the sodium hydride due to steric hindrance toward hydrolysis from the tert-butyl-group. J. AM. CHEM. SOC.
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Table 1. Cyclization of cis-3a under Different Reaction Conditionsa
entry
solvent
catalyst
amount (mol %)
1 2 3 4 5 6 7 8
THF THF THF CH3CN CH3CN toluene toluene AcOH
Pd(PPh3)4 Pd(dba)2 Pd(dba)2 Pd(dba)2 Pd(dba)2 Pd(dba)2 Pd(dba)2 Pd(dba)2
10 13 2 10 2 10 2 10
conv. (%)
reaction time (h)
isolated yield of cis-12 (%)
reaction temp. (°C)
30 100 15 100 100 100 100 100
16 30 15
