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Control of the Regioselectivity in Catalytic Transformations Involving Amphiphilic Bis-allylpalladium Intermediates: Mechanism and Synthetic Applications Niclas Solin, Sanjay Narayan, and Ka´lma´n J. Szabo´*,† Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University, S-106 91 Stockholm, Sweden
[email protected] Received September 15, 2000
Various dialkyl-substituted allyl chloride derivatives (2d-i) undergo regioselective palladiumcatalyzed coupling reactions with allylstannanes (1a,b) and benzylidenemalonitrile (4), providing functionalized 1,7-octadienes in good yield. The catalytic reaction proceeds through an unsymmetrical amphiphilic bis-allylpalladium intermediate. An introductory electrophilic attack on the terminal position of the unsubstituted allyl moiety is followed by a nucleophilic attack on the alkylsubstituted allyl ligand. A theoretical analysis was performed by applying density functional theory at the B3PW91/DZ+P level to study the substituent effects on the electrophilic attack. According to the theoretical results, the high regioselectivity can be ascribed to the electronic effects of the alkyl substituents: The terminal alkyl groups destabilize the η1,η3-bis-allylpalladium intermediate of the reaction; in addition, the alkyl substitution increases the activation barrier for the electrophilic attack. Introduction Allylpalladium chemistry has become one of the most successful areas of organometallic catalysis due to its remarkable capacity for continuous renewal. Catalytic transformations involving nucleophilic attack on (η3allyl)palladium intermediates have been widely applied in a number of important chemical processes1-5 including allylic substitution and the oxidation of alkenes and conjugated dienes. However, recently, catalytic transformations proceeding through an initial electrophilic attack on bis-allylpalladium complexes have attracted much attention.6-12 Furthermore, it has been demonstrated that, under catalytic conditions, bis-allylpalladium complexes can undergo an initial electrophilic attack on one of the allyl moieties followed by a nucleophilic attack on the other.6,11 Thus, bis-allylpalladium intermediates can be classified6 as catalytic amphiphilic species (i.e., they † Fax: +46-8-15 49 08. (1) Tsuji, J. Palladium Reagents and Catalysis: Innovations in Organic Synthesis; Wiley: Chichester, 1995; Chapters 3 and 4. (2) Godleski, S. A. Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Ed.; Pergamon Press: New York, 1991; Vol. 4, Chapter 3.3. (3) Harrington, P. J. Comprehensive Organometallic Chemistry II; Abel, E. W., Gordon, F., Stone, A., Wilkinson, G., Puddephatt, R. J., Eds.; Elsevier: New York, 1995; Vol. 12, p 797. (4) Ba¨ckvall, J.-E. Metal-catalyzed Cross Coupling Reactions; VCH: Weinheim, 1998; p 339. (5) Trost, B. M. Acc. Chem. Res. 1980, 13, 385. (6) Nakamura, H.; Shim, J.-G.; Yamamoto, Y. J. Am. Chem. Soc. 1997, 119, 8113. (7) Nakamura, H.; Nakamura, K.; Yamamoto, Y. J. Am. Chem. Soc. 1998, 120, 4242. (8) Nakamura, K.; Nakamura, H.; Yamamoto, Y. J. Org. Chem. 1999, 64, 2614. (9) Ohno, K.; Tsuji, J. Chem. Commun. 1971, 247. (10) Kiji, J.; Yamamoto, K.; Tomita, H.; Furukawa, J. J. Chem. Soc., Chem. Commun. 1974, 506. (11) Ohno, K.; Mitsuyasu, T.; Tsuji, J. Tetrahedron 1972, 28, 3705. (12) Inoue, Y.; Sasaki, Y.; Hashimoto, H. Bull. Chem. Soc. Jpn. 1978, 51, 2375.
are both electrophilic and nucleophilic), exceptionally useful reagents in organic synthesis. Recently, Yamamoto and co-workers6 reported a synthetically useful reaction in which the bis-allylpalladium intermediate was formed from a mixture of allyltributylstannane (1a) and allyl chloride (2a) in the presence of a palladium catalyst (eq 1). This bis-allylpalladium
intermediate (3, Scheme 1) is attacked by an activated olefin electrophile, such as benzylidenemalonitrile (4), after which a nucleophilic attack takes place on the (mono-) allylpalladium complex formed (Scheme 2), affording a 1,7-octadiene derivative (5). Similar processes using arynes (eq 2) and carbon dioxide (eq 3) instead of 4 have also been reported.13,14 In these publications it was also pointed out that using a different substituent pattern on the allyl chloride and allylstannane components leads to a mixture of isomeric products. When 1a was reacted (13) Yoshikawa, E.; Radhakrishnan, K. V.; Yamamoto, Y. Tetrahedron Lett. 2000, 41, 729. (14) Franks, R. J.; Nicholas, K. M. Organometallics 2000, 19, 1458.
10.1021/jo001374d CCC: $20.00 © 2001 American Chemical Society Published on Web 02/03/2001
Regioselective Control of Bis-allylpalladium Intermediates Scheme 1
J. Org. Chem., Vol. 66, No. 5, 2001 1687 Scheme 3
Scheme 2
with methylallyl chloride (2b) in the presence of a palladium catalyst and aryne, a mixture of benzene derivatives with totally random allylic-allylic addition was obtained (eq 4).13 Palladium-catalyzed mixed car-
attack by 4, the bis-allylation reaction can afford two different isomeric products (Scheme 3). It is interesting to note that the regioselectivity of the electrophilic attack cannot simply be improved by employing the steric effects of the alkyl substituent (eqs 4-6) since the 2-methylallyl and the parent allyl moieties have a similar reactivity. Since the above three-component catalytic procedures have great synthetic potential, improvement of the regiocontrol would considerably enhance the synthetic utility of these reactions. The present study was undertaken to investigate those steric and electronic effects that are responsible for the development of regioselectivity. In this paper we present a substituent pattern, which leads to highly regioselective three-component coupling with alkylallyl chlorides, allylstannanes, and 4. The synthetic studies are also combined with theoretical calculations to gain a better understanding of the reaction mechanism of the catalytic procedure. Experimental Studies
boxylation between 1a and 2b results in a nearly statistical mixture of allyl esters, including all possible homoand cross-coupling products (eq 5).14 We have also found that in the three-component coupling reaction of 1a, 2b, and 4 a statistical mixture of 1,7-octadiene derivatives was formed (eq 6).
Formation of the two different cross-coupling products in these reactions (eqs 4-6) can be easily explained by the accepted mechanism of the catalytic process.6,15,16 Yamamoto and co-workers have shown15 that bis-allylpalladium complexes (3) can be generated from a (mono-)allylpalladium complex and 1a. In the coupling reaction of 1a, 2b, and 4, the Pd(0) catalyst undergoes oxidative addition to 2b, generating a (mono-)allylpalladium complex that reacts with 1a, affording the unsymmetrical bis-allylpalladium complex 3c (Scheme 3). Depending on the location of the introductory electrophilic (15) Nakamura, H.; Iwama, H.; Yamamoto, Y. J. Am. Chem. Soc. 1996, 118, 6641. (16) Szabo´, K. J. Chem. Eur. J. 2000, 6, 4413.
Three-Component Coupling Reaction with Alkylallyl Chloride Derivatives. As mentioned above, the three-component coupling reaction of methylallyl chloride (2b), 1a, and 4 in the presence of a palladium catalyst results in a mixture of four products (eq 6). Using 3-chlorobutene (2c) in place of 2b also leads to a complex reaction mixture including at least three different crosscoupling products and homo-coupling products (eq 7).
However, when we employed 4-alkyl-substituted crotyl chloride derivatives (2d-i) with 1a and 4, just one crosscoupled product was formed (Table 1, entries 1-6) with a remarkably high regioselectivity (eq 8) and in good yield. Furthermore, in these reactions 5 and other homocoupling products were not formed. Although, the regioand chemoselectivity of the reaction is very high, the diastereoselectivity is poor as the different diastereomers formed in a ratio of about 1:1. Using methylallylstannane (1b) and 2b, the expected homo-coupled product (6) was formed (entry 7) in good yield. When 1b was reacted with 2d-i, the very high regioselectivity was maintained (entries 8-13), but 6 was also formed about 1-3%. However, this small amount of
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Table 1. Palladium-Catalyzed Three-Component Coupling Reactions of 1a,b, 2d,i, and 4a
a Reaction conditions: 5 mol % of Pd(PPh ) , 1a,b, 2d-i, and 4 3 4 in CH2Cl2 at 40 °C for 3 h. b Isolated yield.
homo-coupled product can easily be removed by chromatography, and the relatively good yields are still maintained. It is also important to note that the above
Solin et al.
reactions proceed with the same selectivity when a mixture of 2f-i and their corresponding allylic isomers are used as the chloride component. Regioselectivity of the Electrophilic and Nucleophilic Attack. The very high regioselectivity is a synthetically useful feature of the above three-component coupling reactions (eq 8). The possible pathways involving the different electrophilic and nucleophilic attacks are given in Scheme 4. The first step is an oxidative addition of the palladium(0) catalyst to 2d-i (or the corresponding allylic isomers), which results in (mono-)allylpalladium complex 19. This complex reacts with 1a,b, giving the unsymmetrical bis-allylpalladium complex 3d or its η1,η3isomer (vide infra). When the electrophilic attack takes place at the terminal-substituted allyl moiety, two different products can be formed (20a and 20b) unless the terminal substituents are identical (entries 1-2 and 8-9). The subsequent nucleophilic attack on 20a and 20b gives 21a and 21b, respectively, along with regeneration of Pd(0). On the other hand, an incipient electrophilic attack at the central or nonsubstituted allyl moiety of 3d (or its η1,η3-isomer) affords 22, which can undergo nucleophilic attack at the more or at the less substituted allylic terminus providing 23a and 23b. Accordingly, when the two terminal substituents of 3d are different (entries 3-6 and 10-13), a total of four different regioisomers (21a,b and 23a,b) can be formed. Even with identical terminal substituents (entries 1-2 and 8-9), two different regioisomers are expected. However, in the reactions described by eq 8 only a single regioisomer corresponding to 23a is formed. This isomer can only be formed by an exclusive attack at the central or nonsubstituted allylic moiety of 3d followed by a nucleophilic attack at 22. Formation of 23a alone also involves a highly regioselective nucleophilic attack on 22. The high level of regiochemistry of the nucleophilic attack on similar types of (mono-)allylpalladium intermediates has been studied by Keinan and Sahai.17 These authors found that malonate type nucleophiles attack the less substituted allylic moiety with a remarkably high regioselectivity.17 A nucleophilic attack by a bulky malonate congener at the methyl-substituted allylic terminus in 22 provides 23a, in line with the findings of Keinan and Sahai.17 The most interesting feature of the above-discussed reactions (eqs 6-8) is certainly the dependence of the regiochemistry of the incipient electrophilic attack on the substituent pattern of the substrates. In the presence of two terminal substituents on one of the allyl moieties in the unsymmetrical bis-allylpalladium intermediate, as in 3d, a very high regioselectivity occurs (eq 8); however when the intermediate is mono-alkyl substituted (Scheme 3, eqs 6-7), the regioselectivity is poor and, in addition, homo-coupling readily takes place. A possible explanation for the formation of homocoupled products is the exchange of the allyl groups between the (mono-)allylpalladium (19) and bisallylpalladium species (3d). This process has been studied by Yamamoto and co-workers15 using the dynamic NMR technique. In such a process, an unsymmetrical bisallylpalladium complex (3c) can be converted to a symmetrical one (3a), giving a homo-coupling product (5). Fortunately, this processes is suppressed by using allyl (17) Keinan, E.; Sahai, M. J. Chem. Soc., Chem. Commun. 1984, 648.
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J. Org. Chem., Vol. 66, No. 5, 2001 1689
Scheme 4
chlorides 2d-i in the three-component coupling reactions. One possible explanation is that the exchange of a terminal-substituted allylic moiety in 3d is slower than the electrophilic attack of this complex. Theoretical Studies We have carried out DFT calculations (Figures 1 and 2) with the aim of examining the electronic and steric effects of the alkyl substituents on the regiochemistry of the electrophilic attack in the three-component coupling reactions discussed above. In a recent theoretical study16 it was shown that the electrophilic attack proceeds through the η1,η3-form of the bis-allylpalladium complexes and that the electrophilic attack on the η1-allyl moiety of these complexes (eq 9) occurs with a remarkably low activation energy.
Computational Methods. All geometries were fully optimized by employing a Becke-type18 three-parameter density functional model, B3PW91. This so-called hybrid functional includes the exact (Hartree-Fock) exchange, the gradient-corrected exchange functional introduced by Becke,18 and the more recent correlation functional of Perdew and Wang.19 All calculations have been carried (18) Becke, A. D. J. Chem. Phys. 1993, 98, 5648.
out using a double-ζ(DZ)+P basis constructed from the LANL2DZ basis20-22 by adding one set of d-polarization functions to the heavy atoms (exponents: C, 0.63; N, 0.864, P, 0.34) and one set of diffuse d-functions for palladium (exponent: 0.0628). Harmonic frequencies have been calculated at the level of optimization for all structures to characterize the calculated stationary points and to determine the zero-point energies (ZPE). Fully optimized transition state structures 27a, 28a, and 29a have been characterized by a single imaginary frequency, while the rest of the fully optimized structures possess only real frequencies. All calculations have been conducted by employing the Gaussian 98 program package.23 The theoretical studies involve an investigation the electrophilic attack on the parent (25) and on 1,3dimethyl-substituted (26a and 26b) bis-allylpalladium complexes. Reactant 4 is modeled by acrylonitrile (AN) and the PPh3 ligand is replaced by PH3 to reduce the computational burden of the study. (19) Perdew, J. P.; Wang, Y. Phys. Rev. B 1992, 45, 13244. (20) Dunning, T. H.; Hay, P. J. Modern Theoretical Chemistry; Plenum: New York, 1977; Vol. 3; p 1. (21) Hay, P. J.; Wadt, W. R. J. Chem. Phys. 1985, 82, 270. (22) Hay, P. J.; Wadt, W. R. J. Chem. Phys. 1985, 82, 299. (23) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Zakrzewski, V. G.; Montgomery, J. A.; Stratmann, R. E.; Burant, J. C.; Dapprich, S.; Millam, J. M.; Daniels, A. D.; Kudin, K. N.; Strain, M. C.; Farkas, O.; Tomasi, J.; Barone, V.; Cossi, M.; Cammi, R.; Mennucci, B.; Pomelli, C.; Adamo, C.; Clifford, S.; Ochterski, J.; Petersson, G. A.; Ayala, P. Y.; Q. Cui; Morokuma, K.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Cioslowski, J.; Ortiz, J. V.; Stefanov, B. B.; G. Liu; Liashenko, A.; Piskorz, P.; Komaromi, I.; Gomperts, R.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; A. Nanayakkara; Gonzalez, C.; Challacombe, M.; Gill, P. M. W.; Johnson, B.; W. Chen; Wong, M. W.; Andres, J. L.; Gonzalez, C.; M. Head-Gordon; Replogle, E. S.; Pople, J. A. Gaussian 98; Gaussian, Inc.: Pittsburgh, PA, 1998.
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Figure 1. Selected B3PW91/LANL2DZ+P geometrical parameters for bis-allylpalladium complexes, TS structures, and products of the electrophilic attack by acrylonitrile (bond lengths in Å, energies in kcal/mol). The zero-point vibration corrected energies are given in italics. The numberation of the allyl moieties is given in Scheme 1.
Stability of the η1,η3-bis-Allylpalladium Complexes. In the presence of π-acceptor ligands (such as PH3), the η3,η3-bis-allylpalladium complexes (3a and 24) are converted to the corresponding η1,η3-forms (25, 26a, and 26b) in an exothermic reaction. From an unsymmetrical η3,η3-complex, such as 24, at least two different η1,η3-bis-allylpalladium complexes can be formed, 26a and 26b. The effects of the allylic methyl substituents on the stability of the η1,η3-forms depend on the coordina-
tion state (η1 or η3) of the allyl moiety. The η3-dimethylsubstituted complex (26b) is more stable by 3 kcal/mol than its η1-dimethyl-substituted counterpart (26a). Interestingly, the formation of 26b (-19.6 kcal/mol) is about as exothermic as the formation of the unsubstituted complex 25 (-19.2 kcal/mol), also suggesting that the energy difference between 26a and 26b cannot be explained only by the steric effects of the methyl substituents.
Regioselective Control of Bis-allylpalladium Intermediates
Figure 2. Energy profiles for the reaction of bis-allylpalladium complexes 3a and 24 with acrylonitrile (AN) in the presence of the PH3 ligand. All energies are given in kcal/mol.
The methyl carbons are close to palladium in both 26a and 26b. In 26a the Pd-C(C4) distance (3.07 Å) is shorter (see Scheme 1 for numberation of the allyl moiety) than the corresponding distance in 26b (Pd-C(C1) ) 3.25 Å, and Pd-C(C3) ) 3.43 Å). However, in 26b both methyl groups are involved in repulsive interactions with palladium, while in 26a the C6 methyl substituent is far away from the central atom. It can, therefore, be assumed that the steric effects of the methyl group(s) destabilizes 26a and 26b to a similar extent. On the other hand, the electronic effects of the methyl substituents in 26a and 26b are basically different. An important destabilizing factor in 26a is an electronic interaction between the filled σ(Pd-C4) and the pseudo-πCH3 MOs. This is a fourelectron interaction, which is closely related to the n-πCH3 interaction destabilizing sp3 alkyl anions, such as the ethyl anion.24 Terminal methyl substituents on the η3coordinated allyl (26b) do not experience this destabilizing interaction, leading to a more stable η1,η3-bisallylpalladium complex. Electrophilic Attack by Acrylonitrile. The electrophilic attack on 25 and 26a,b proceeds through TS structures 27a, 28a, and 29a, respectively (Figure 2). The activation energy of the electrophilic attack on the unsubstituted complex 25 (14.2 kcal/mol) is somewhat higher than that of the η3-methyl-substituted complex 26b (12.9 kcal/mol). However, the activation barrier to the electrophilic attack on the η1-methyl-substituted complex 26a is considerably higher (by 2.9 kcal/mol) than the activation barrier to the reaction for its η3-methylsubstituted counterpart 26b. This clearly indicates that the methyl-substituted carbon (C6) in 26a is much less nucleophilic than the unsubstituted terminal carbon in 25 and 26b. This reactivity feature and the higher thermodynamic stability of 26b work in the same direction and make the 24 f 26b f 29a f29b pathway more favorable than the competing 24 f 26a f 28a f28b pathway. Thus, the electrophilic attack on an unsymmetrically substituted bis-allylpalladium (24) takes place at the unsubstituted allyl moiety in complete agreement with our experimental findings (Scheme 4, Table 1). Formation of the reaction products 27b, 28b, and 29b is an exothermic process. Because of the high exother(24) Albright, T. A.; Burdett, J. K.; Whangbo, M.-H. Orbital Interactions in Chemistry; Wiley: New York, 1985; p 152.
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micity (-24-25 kcal/mol) the electrophilic attack is an irreversible step. In the product complexes the cyanohexenyl moiety is η1-coordinated to palladium. This cyanohexenyl moiety is also a potential nucleophile, which can subsequently attack the η3-allyl moiety of the complex. Relevance of the Theoretical Results in the Chemistry of Bis-allylpalladium Complexes. Formation of an unsymmetrical η3,η3-bis-allylpalladium intermediate in the palladium-catalyzed three-component coupling reactions involves the fact that electrophilic and subsequent nucleophilic attack can afford up to four isomeric products (Scheme 4). The η3,η3-bis-allylpalladium intermediate is converted to various η1,η3-form isomers in the presence of π-acceptor ligands. The above theoretical calculations clearly indicate that the electronic effects of the alkyl substituents on the stability of the η1,η3 complexes depend on the coordination state of the substituted allyl moiety: An alkyl substituent at the metalated terminal carbon (C4 in 26a) destabilizes the complex. Furthermore, an alkyl substituent decreases the nucleophilicity of the attacked carbon (C6 in 26a), and therefore the activation barrier to the electrophilic attack is higher for a terminally alkylated η1-moiety (28a) than for an unsubstituted one (29a). Accordingly, with an appropriate choice of the substituent pattern, the regioselectivity of the electrophilic attack can be fully controlled. A substituent pattern providing a high level of regioselectivity in the electrophilic attack requires terminal alkyl substituents at one of the allyl moieties in the bisallylpalladium intermediate and unsubstituted terminal carbons at the other (cf. 3d). This substituent pattern guarantees that the introductory electrophilic attack occurs at the unsubstituted allyl moiety. The different bulk of the alkyl substituents helps to control even the regiochemistry of the nuclephilic attack.17 If one is to employ terminal substituents other than alkyl groups, the substituent effects on the stability of the various η1,η3bis-allylpalladium intermediates will have to be carefully analyzed. Such an analysis can easily be done using the above theoretical model. Concluding Remarks In this study we have shown that the three-component coupling reactions of allylstannanes 1a,b, allyl chlorides 2d-i, and benzylidenemalonitrile proceed with excellent regiochemistry and with good yields. The theoretical calculations indicate that the high regioselectivity can be ascribed to the electronic effects of the alkyl substituents. The terminal alkyl substituents in the bis-allylpalladium intermediate of the reaction have two important effects: destabilization of the η1,η3-bis-allylpalladium intermediate when the η1-moiety is substituted and an increase in the activation barrier of the electrophilic attack brought about by the alkyl substitution.
Experimental Section The starting materials were purchased from Aldrich or Lancaster. The alkylallyl chlorides and 2-methylallyltributyltin were prepared using standard literature procedures.25-29 (25) Brooks, L. A.; Snyder, H. R. Organic Syntheses; Wiley: New York, 1955; Collect. Vol. III, p 698. (26) Magid, R. M.; Fruchey, O. S.; Johnson, W. L.; Allen, T. G. J. Org. Chem. 1979, 44, 359.
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J. Org. Chem., Vol. 66, No. 5, 2001
Thesolvents were freshly distilled prior to use. All reactions were conducted under an argon atmosphere by employing standard manifold techniques. The 1H and 13C NMR spectra were recorded in CDCl3 solutions at 300 and 75 MHz, respectively, at room temperature. The chemical shifts (ppm) are obtained using CDCl3 as an internal standard (7.26 ppm, 1 H; 77.36 ppm, 13C). Merck silica gel 60 (230-400 mesh) was used for the chromatography. General Procedure. A mixture of the corresponding allyl chloride (0.38 mmol), benzylidenemalonitrile (0.32 mmol), and Pd(PPh3)4 (0.016 mmol, 5 mol %) in dichloromethane (1 mL) was stirred for 15 min at room temperature. Then, allylstannane (0.38 mmol) was added, and the reaction mixture was stirred for 3 h at 40 °C. The reaction mixture was diluted with ether (5 mL) and treated with a saturated KF solution. After filtration, the organic phase was washed with water and brine, dried over MgSO4, and concentrated. The products were isolated by silica gel chromatography using a pentane-ether eluent. The two diastereomers formed could usually be separated by chromatography (the exceptions were 8 and 14) so the NMR data of the diastereomeric forms is given separately. 4,4-Dicyano-2,7-dimethyl-5-phenylocta-1,7-diene (6). 1 H NMR: δ 7.38 (m, 5H), 5.12 (m, 1H), 5.03 (m, 1H), 4.70 (br s, 1H), 4.63 (br s, 1H), 3.24 (dd, J ) 10.0 and 5.2 Hz, 1H), 2.90 (m, 2H), 2.48 (d, J ) 14.0 Hz, 1H), 2.25 (d, J ) 14.0 Hz, 1H), 1.90 (s, 3H), 1.62 (s, 3H). 13C NMR: δ 140.7, 137.8, 135.6, 129.4, 129.3, 129.2, 118.7, 116.1, 115.2, 114.9, 51.6, 44.5, 42.9, 40.3, 23.4, 22.5. MS (EI): m/z (rel intensity) 265 (M+ + 1, 10), 249 (17), 145 (100), 117 (60), 77 (6). 5,5-Dicyano-6-methyl-4-phenylnona-1,7-diene (7). 1H NMR: δ 7.35 (m, 5H), 5.45 (m, 3H), 5.03 (dd, J ) 16.8 and 1.5 Hz, 1H), 4.94 (dd, J ) 9.9 and 1.8 Hz, 1H), 3.08 (dd, J ) 11.7 and 4.5 Hz, 1H), 2.86 (m, 2H), 2.37 (m, 1H), 1.76 (d, J ) 4.8 Hz, 3H), 1.31 (d, J ) 6.9 Hz, 3H). 13C NMR: δ 135.5, 133.9, 132.1, 129.4, 129.0, 128.9, 127.4, 118.5, 115.1, 115.0, 49.8, 49.8, 41.9, 37.8, 18.8, 18.5.; 1H NMR: δ 7.39 (m, 5H), 5.70 (m, 1H), 5.47 (m, 2H), 5.03 (dd, J ) 17.2 and 2.0 Hz, 1H), 4.95 (dd, J ) 9.6 and 2.0 Hz, 1H), 3.11 (dd, J ) 9.2 and 6.0 Hz, 1H), 2.80 (m, 2H), 2.55 (m, 1H), 1.76 (dd, J ) 6.4 and 1.6 Hz, 3H), 1.34 (d, 6.8 Hz, 3H).13C NMR: δ 136.3, 134.0, 131.7, 129.3, 129.2, 129.0, 128.3, 118.5, 115.2, 114.5, 49.4, 49.3, 42.3, 36.0, 18.3, 17.1. Anal. Calcd for C18H20N2: C, 81.78; H, 7.63; N, 10.60. Found: C, 81.79; H, 7.80; N, 10.45. 5-(Cyclohex-2-enyl)-5,5-dicyano-4-phenylpent-1-ene (8). 1 H NMR: δ 7.38 (m, 10H), 6.11-6.04 (br m, 2H), 5.75 (m, 2H), 5.51 (m, 2H), 5.07 (m, 2H), 4.97 (m, 2H), 3.31 (dd, J ) 10.4 and 5.2 Hz, 1H), 3.20 (dd, J ) 10.8 and 4.8 Hz, 1H), 2.91 (m, 4H), 2.42-2.40 (br m, 2H), 2.15-2.06 (br m, 6H), 1.91-1.89 (br m, 2H), 1.72-1.55(br m, 2H), 1.50-1.40 (br m, 2H). 13C NMR: δ 135.6, 135.6, 134.7, 134.2, 133.9, 133.9, 129.4, 129.3, 129.3, 129.1, 129.0, 129.0, 123.8, 122.1, 118.6, 115.3, 115.2, 115.0, 114.4, 48.8, 48.8, 48.7, 48.5, 40.3, 39.9, 37.5, 36.6, 26.6, 25.0, 25.0, 24.9, 21.3, 21.3. MS (EI): m/z (rel intensity) 277 (M+ + 1, 10), 131 (100), 81 (39), 77 (5). 5,5-Dicyano-6,9-dimethyl-4-phenyldeca-1,7-diene (9). 1H NMR: δ 7.35 (m, 5H), 5.40 (m, 3H), 5.03 (dd, J ) 17.1 and 1.5 Hz, 1H), 4.94 (dd, J ) 10.2 and 1.8 Hz, 1H), 3.05 (dd, J ) 11.4 and 4.2 Hz, 1H), 2.88 (m, 2H), 2.34 (m, 2H), 1.32 (d, J ) 6.6 Hz, 3H), 1.06 (d, J ) 6.9 Hz, 3H), 1.01 (d, J ) 6.9 Hz, 3H).13C NMR: δ 144.3, 135.5, 133.9, 129.5, 129.0, 128.9, 123.3, 118.5, 115.1, 115.1, 49.9, 48.8, 41.9, 37.9, 31.8, 22.7, 22.5, 19.1. MS (EI): m/z (rel intens) 292 (M+, 2), 277 (6), 251 (5), 131 (100), 91 (34), 77 (2), 69 (14). 1H NMR: δ 7.38 (m, 5H), 5.65 (dd, J ) 15.6 and 6.9 Hz, 1H), 5.44 (m, 2H), 5.02 (dd, J ) 17.1 and 1.8 Hz, 1H), 4.94 (dd, J ) 10.2 and 1.8 Hz, 1H), 3.10 (dd, J ) 9.3 and 6.0 Hz, 1H), 2.79 (m, 2H), 2.53 (m, 1H), 2.35 (m, 1H), 1.34 (d, J ) 6.9 Hz, 3H), 1.03 (d, J ) 6.9 Hz, 3H), 1.01 (d, J ) 6.9 Hz, 3H).13C NMR: δ 144.1, 136.2, 133.9, 129.2, 129.1, 129.0, 124.1, 118.5, 115.1, 114.3, 49.5, 49.4, 42.3, 35.9, 31.6, 22.7, 22.7, 17.4. MS (EI): m/z (rel intensity) 292 (M+, 3), 277 (7), 251 (7), 131 (100), 91 (19), 77 (2), 69 (4). (27) Renaud, P.; Fox, M. A. J. Org. Chem. 1988, 53, 3754. (28) Still, W. C. J. Am. Chem. Soc. 1976, 100, 1481. (29) Mori, K.; Waku, M.; Sakakibara, M. Tetrahedron 1985, 41, 2825.
Solin et al. 5,5-Dicyano-8-cyclohexyl-6-methyl-4-phenylocta-1,7diene (10). 1H NMR: δ 7.35 (m, 5H), 5.44 (m, 1H), 5.37 (m, 2H), 5.02 (dd, J ) 17.2 and 1.2 Hz, 1H), 4.93 (dd, J ) 9.6 and 1.2 Hz, 1H), 3.05 (dd, J ) 11.7 and 4.2 Hz, 1H), 2.88 (m, 2H), 2.33 (m, 1H), 2.04-1.97 (br m, 1H) 1.81-1.65 (br m, 5H), 1.31 (d, J ) 6.9 Hz, 3H), 1.40-1.05 (m, 5H). 13C NMR: δ 143.2, 135.5, 133.9, 129.5, 129.0, 128.9, 123.7, 118.5, 115.1, 115.1, 49.9, 48.8, 42.0, 41.3, 37.9, 33.2, 33.1, 26.4, 26.3, 19.1. MS (EI): m/z (rel intensity) 332 (M+, 3), 131 (64), 81 (100), 77 (6). 1 H NMR: δ 7.38 (m, 5H), 5.64 (dd, J ) 15.3 and 9.2 Hz, 1H), 5.50-5.30 (br m, 2H), 5.02 (dd, J ) 17.1 and 1.8 Hz, 1H) 4.95 (dd, J ) 10.2 and 1.8 Hz, 1H), 3.10 (dd, J ) 9.3 and 6.3 Hz, 1H), 2.76 (m, 2H), 2.55 (m, 1H), 2.10-1.95 (br m, 1H) 1.801.60 (br m, 5H), 1.34 (d, J ) 6.6 Hz, 3H), 1.40-1.05 (m, 5H). 13C NMR: δ 142.9, 136.3, 133.9, 129.2, 129.2, 129.0, 124.5, 118.5, 115.2, 114.3, 49.6, 49.4, 42.5, 41.1, 35.8, 33.2, 33.2, 26.4, 26.3, 17.5. MS (EI): m/z (rel intensity) 332 (M+, 2), 131 (60), 81 (100), 77 (7). 5,5-Dicyano-6-methyl-4,9-diphenylnona-1,7-diene (11). 1H NMR: δ 7.27 (m, 10H), 5.51 (m, 3H), 4.98 (m, 2H), 3.42 (d, J ) 6.6 Hz, 2H), 3.02 (dd, J ) 11.6 and 4.4 Hz, 1H), 2.87 (m, 2H), 2.40 (m, 1H), 1.36 (dd, J ) 6.8 and 1.1 Hz, 3H).13C NMR: 139.6, 136.1, 135.4, 133.8, 129.4, 129.0, 128.9, 128.8, 128.7, 127.2, 126.7, 118.5, 115.1, 115.0, 50.0, 48.7, 41.8, 39.6, 38.0, 18.8. 1H NMR: δ 7.37 (m, 5H), 7.27 (m, 5H), 5.84 (m, 1H), 5.56 (m, 1H), 5.39 (m, 1H), 4.96 (dd, J ) 17.1 and 1.5 Hz, 1H), 4.91 (dd, J ) 10.2 and 1.5 Hz, 1H), 3.44 (d, J ) 6.9 Hz, 2H), 3.10 (dd, J ) 9.6 and 6.0 Hz, 1H), 2.78 (m, 2H), 2.60 (m, 1H), 1.37 (d, J ) 6.9 Hz, 3H).13C NMR: δ 139.6, 136.1, 135.5, 133.7, 129.3, 129.1, 129.0, 128.9, 128.7, 128.4, 126.6, 118.6, 115.0, 114.3, 49.4, 49.4, 42.3, 39.3, 36.0, 17.2. Anal. Calcd for C24H24N2: C, 84.67; H, 7.11; N, 8.23. Found: C, 84.58; H, 7.26; N, 8.23. 7,7-Dicyano-6-methyl-8-phenylundeca-1,4,10-triene (12). 1H NMR: δ 7.35 (m, 5H), 5.82 (m, 1H), 5.45 (m, 3H), 5.09 (m, 2H), 5.03 (dd, J ) 17.0 and 1.4 Hz, 1H), 4.94 (dd, J ) 10.2 and 1.1 Hz, 1H), 3.07 (dd, J ) 11.6 and 4.1 Hz, 1H), 2.87 (m, 4H), 2.41 (m, 1H), 1.34 (d, J ) 6.9 Hz, 3H). 13C NMR: 135.8, 135.4, 134.8, 133.8, 129.5, 129.0, 128.9, 127.2, 118.5, 116.5, 115.1, 114.9, 49.9, 48.7, 41.9, 37.8, 37.1, 18.9. 1H NMR: δ 7.38 (m, 5H), 5.70 (m, 2H), 5.45 (m, 2H), 4.98 (m, 4H), 3.10 (dd, J ) 9.6 and 6.0 Hz, 1H), 2.80 (m, 4H), 2.54 (m, 1H), 1.36 (d, J ) 6.6 Hz, 3H). 13C NMR: δ 136.1, 135.8, 134.3, 133.8, 129.2, 129.1, 129.0, 128.2, 118.5, 116.4, 115.0, 114.3, 49.4, 49.3, 42.3, 36.8, 36.1, 17.2. Anal. Calcd for C20H22N2: C, 82.72; H, 7.64; N, 9.65. Found: C, 82.56; H, 7.53; N, 9.79. 5,5-Dicyano-2,6-dimethyl-4-phenylnona-1,7-diene (13). 1H NMR: δ 7.34 (m, 5H), 5.47 (m, 2H), 4.66 (s, 1H), 4.56 (s, 1H), 3.21 (dd, J ) 10.8 and 4.4 Hz, 1H), 2.83 (m, 2H), 2.38 (m, 1H), 1.77 (d, J ) 4.9 Hz, 3H), 1.57 (s, 3H) 1.32 (d, J ) 6.9 Hz, 3H). 13C NMR: δ 140.9, 135.8, 132.2, 129.5, 128.9, 127.5, 115.3, 115.1, 114.9, 49.0, 48.4, 41.9, 41.6, 22.5, 18.7, 18.4. MS (EI): m/z (rel intensity) 279 (M+ + 1, 11), 263 (20), 145 (100), 117 (49), 77 (2). 1H NMR: δ 7.37 (m, 5H), 5.72 (m, 1H), 5.49 (m, 1H), 4.67 (m, 1H), 4.58 (s, 1H), 3.24 (dd, J ) 11.2 and 4.4 Hz, 1H), 2.74 (m, 2H), 2.58 (m, 1H), 1.77 (dd, J ) 6.8 and 1.6 Hz, 3H), 1.55 (s, 3H), 1.35 (d, 7.2 Hz, 3H). 13C NMR: δ 140.8, 136.5, 131.7, 129.2, 129.1, 129.0, 128.3, 115.3, 115.0, 114.5, 49.5, 47.9, 42.5, 39.5, 22.4, 18.3, 17.4. MS (EI): m/z (rel intensity) 279 (M+ + 1, 2), 263 (17), 145 (100), 117 (51), 77 (3). 5,5-Dicyano-5-(cyclohex-2-enyl)-2-methyl-4-phenylpent1-ene (14). 1H NMR: δ 7.36 (m, 10H), 6.11-6.06 (br m, 2H), 5.78-5.72 (br m, 2H), 4.69 (s, 2H), 4.62 (s, 1H), 4.59 (s, 1H), 3.43 (dd, J ) 10.5 and 4.5 Hz, 1H), 3.33 (dd, J ) 9.3 and 5.7 Hz, 1H), 2.85 (m, 4H), 2.43-2.37 (br m, 2H), 2.13-2.04 (br m, 6H), 1.94-1.87 (br m, 2H), 1.61 (s, 3H), 1.60 (s, 3H), 1.701.54 (br m, 2H), 1.49-1.43 (br m, 2H). 13C NMR: δ 140.7, 135.7, 135.7, 134.7, 134.2, 129.2, 129.1, 129.0, 128.9, 128.9, 123.7, 122.1, 115.4, 115.2, 115.1, 114.9, 114.8, 114.5, 49.2, 47.4, 47.3, 41.5, 40.6, 40.5, 40.1, 26.8, 25.2, 25.0, 22.7, 22.6, 21.5, 21.4. Anal. Calcd for C20H22N2: C, 82.72; H, 7.64; N, 9.65. Found: C, 82.54; H, 7.76; N, 9.60. 5, 5-Dicyano-2,6,9-trimethyl-4-phenyldeca-1,7-diene (15). 1H NMR: δ 7.34 (m, 5H), 5.39 (m, 2H), 4.65 (m, 1H), 4.55 (m, 1H), 3.20 (dd, J ) 11.2 and 4.1 Hz, 1H), 2.82 (m, 2H), 2.35 (m,
Regioselective Control of Bis-allylpalladium Intermediates 2H), 1.57 (s, 3H) 1.32 (d, J ) 6.9 Hz, 3H), 1.07 (d, J ) 6.8 Hz, 3H), 1.02 (d, J ) 6.8 Hz, 3H). 13C NMR:144.4, 140.7, 135.6, 129.5, 128.8, 123.4, 115.2, 115.1, 114.8, 49.1, 48.5, 42.0, 41.8, 31.8, 22.8, 22.6, 22.6, 19.1. MS (EI): m/z (rel intensity) 306 (M+, 3), 291 (10), 263 (49), 145 (100), 117 (69), 69 (16). 1H NMR: δ 7.37 (m, 5H), 5.67 (dd, J ) 15.4 and 6.9 Hz, 1H), 5.40 (ddd, J ) 15.4 and 9.3 and 1.4 Hz, 1H), 4.66 (m, 1H), 4.59 (s, 1H), 3.25 (dd, J ) 11.2 and 4.1 Hz, 1H), 2.77 (m, 2H), 2.57 (m, 1H), 2.36 (m, 1H), 1.56 (s, 3H), 1.36 (d, J ) 6.6 Hz, 3H), 1.04 (d, J ) 6.8 Hz, 3H), 1.02 (d, J ) 6.8 Hz, 3H). 13C NMR: δ 144.2, 140.8, 136.6, 129.2, 129.2, 129.0, 124.3, 115.3, 115.0, 114.4, 49.7, 47.8, 42.3, 39.4, 31.6, 22.6, 22.6, 22.5, 17.6. MS (EI): m/z (rel intensity) 306 (M+, 3), 291 (10), 263 (15), 145 (100), 117 (37), 69 (15). 5,5-Dicyano-8-cyclohexyl-2,6-dimethyl-4-phenylocta1,7-diene (16). 1H NMR: δ 7.33 (m, 5H), 5.39 (m, 2H), 4.65 (s, 1H), 4.55 (s, 1H), 3.20 (dd, J ) 11.1 and 4.5 Hz, 1H), 2.82 (m, 2H), 2.32 (m, 1H), 2.07-1.99 (br m, 1H) 1.79-1.67 (br m, 5H), 1.57 (s, 3H) 1.32 (d, J ) 6.9 Hz, 3H), 1.40-1.05 (m, 5H). 13C NMR: δ 143.4, 140.9, 135.7, 129.6, 128.9, 123.9, 115.3, 115.2, 114.8, 49.0, 48.4, 42.0, 41.7, 41.2, 33.2, 33.1, 26.3, 26.2, 22.5, 19.0. 1H NMR: δ 7.36 (m, 5H), 5.65 (dd, J ) 15.4 and 6.8 Hz, 1H), 5.39 (ddd, J ) 15.4 and 9.1 and 1.1 Hz, 1H), 4.66 (d, J ) 0.8 Hz, 1H) 4.59 (s, 1H), 3.25 (dd, J ) 11.6 and 4.1 Hz, 1H), 2.73 (m, 2H), 2.58 (m, 1H), 2.07-1.98 (br m, 1H) 1.751.65 (br m, 5H), 1.55 (s, 3H),1.36 (d, J ) 6.6 Hz, 3H), 1.351.05 (m, 5H). 13C NMR: δ 143.0, 140.8, 136.6, 129.2, 129.1, 129.0, 124.7, 115.3, 115.0, 114.4, 49.7, 47.7, 42.4, 41.1, 39.3, 33.2, 33.1, 26.3, 26.2, 22.6, 17.7. Anal. Calcd for C24H30N2: C, 83.19; H, 8.73; N, 8.08. Found: C, 83.01; H, 8.92; N, 8.07. 5,5-Dicyano-2,6-dimethyl-4,9-diphenylnona-1,7-diene (17). 1H NMR: δ 7.35-7.10 (br m, 10H), 5.62 (m, 1H), 5.51 (m, 1H), 4.63 (s, 1H), 4.51 (s, 1H), 3.42 (d, J ) 6.6 Hz, 2H), 3.13 (dd, J ) 11.5 and 4.1 Hz, 1H), 2.79 (m, 2H), 2.37 (m, 1H), 1.56 (d, J ) 6.8, 3H), 1.36 (d, J ) 6.6 Hz, 3H). 13C NMR: δ 140.7, 139.8, 136.4, 135.5, 129.4, 129.1, 128.9, 128.9, 128.8, 127.3, 126.8, 115.2, 115.1, 114.9, 48.9, 48.4, 41.9, 41.8, 39.5, 22.4, 18.7. MS (EI): m/z (rel intensity) 354 (M+, 2), 263 (47), 145 (100), 117 (38), 91 (11). 1H NMR: δ 7.36 (m, 5H), 7.27 (m,
J. Org. Chem., Vol. 66, No. 5, 2001 1693 5H), 5.86 (m, 1H), 5.56 (m, 1H), 4.63 (s, 1H), 4.53 (s, 1H), 3.44 (d, 6.9 Hz, 2H), 3.23 (dd, J ) 11.0 and 4.3 Hz, 1H), 2.64 (m, 3H), 1.45 (s, 3H), 1.38 (d, 6.6 Hz, 3H). 13C NMR: δ 140.6, 139.5, 136.3, 135.7, 129.1, 128.9, 128.9, 128.8, 128.3, 126.7, 115.1, 114.9, 114.3, 49.6, 47.8, 42.3, 39.6, 39.4, 22.5, 17.5. MS (EI): m/z (rel intensity) 354 (M+, 4), 263 (16), 145 (100), 117 (39), 91 (13). 7,7-Dicyano-6,10-dimethyl-8-phenylundeca-1,4,10triene (18). 1H NMR: δ 7.34 (m, 5H), 5.83 (m, 1H), 5.50 (m, 2H), 5.10 (m, 2H), 4.66 (m, 1H), 4.56 (m, 1H), 3.20 (dd, J ) 10.8 and 4.8 Hz, 1H), 2.84 (m, 4H), 2.41 (m, 1H), 1.57 (s, 3H), 1.35 (d, J ) 6.9 Hz, 3H).13C NMR: δ 140.6, 135.8, 135.5, 134.8, 129.4, 128.8, 127.3, 116.4, 115.1, 114.9, 114.7, 48.9, 48.4, 41.9, 41.6, 37.0, 22.5, 18.8. MS (EI): m/z (rel intensity) 305 (M+ + 1, 1), 263 (41), 145 (100), 117 (45), 77 (7), 67 (50). 1H NMR: δ 7.37 (m, 5H), 5.81 (m, 1H), 5.78 (m,1H), 5.50 (m, 1H), 5.09 (dd, J ) 14.0 and 1.6 Hz, 1H), 5.06 (dd, J ) 7.2 and 1.6 Hz, 1H) 4.67 (m, 1H), 4.58 (s, 1H), 3.25 (dd, J ) 11.2 and 4.4 Hz, 1H), 2.84 (m, 2H), 2.75 (m, 2H), 2.59 (m, 1H), 1.56 (s, 3H), 1.36 (d, J ) 6.4 Hz, 3H).13C NMR: δ 140.7, 136.4, 135.9, 134.5, 129.2, 129.0, 128.3, 116.6, 115.2, 115.0, 114.4, 49.5, 47.9, 42.3, 39.6, 36.8, 22.5, 17.4. MS (EI): m/z (rel intensity) 305 (M+ + 1, 1), 263 (10), 145 (100), 117 (47), 77 (5), 67 (37).
Acknowledgment. This work was supported by the Swedish Natural Science Research Council (NFR). The calculations were done at the IBM SP2 parallel computer facility of the Parallelldatorcentrum (PDC) at the Royal Institute of Technology, Sweden. The authors thank the PDC for a generous allotment of computer time. The financial support of The Wenner-Gren Foundations for a postdoctoral fellowship to S.N. is gratefully acknowledged. Supporting Information Available: 13C NMR spectra for compounds 6, 8-10, 13, 15, 17, and 18. This material is available free of charge via the Internet at http://pubs.acs.org. JO001374D
