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Cycloadditions of Ketene Diethyl Acetal and 2-Methylene-1,3-dioxepane to Electrophilic Alkenes† Keith Johnston, Anne Buyle Padias, Robert B. Bates, and H. K. Hall, Jr.* Department of Chemistry, University of Arizona, Tucson, Arizona 85721 Received December 23, 2002. In Final Form: March 12, 2003 Reactions of strong electron-rich donor alkenes with strong electron-poor acceptor alkenes give a variety of products, including cyclobutanes, cyclohexanes composed of two alkenes of one kind and one of the other, open chain adducts, and homopolymers of the alkenes. We examined cycloadditions of ketene diethyl acetal and 2-methylene-1,3-dioxepane to alkenes containing from one to four acceptor groups. The products and rates, in particular the structure of the cyclohexane adducts produced, are correlated with the ionic homopolymerizability of the alkenes, zwitterion stabilization, and gem-dialkyl cyclization effects. These concepts are extended to enamines and enolate anions as other electron-rich alkenes. 2-Methylene-1,3dioxepane is the ketene acetal of choice for the preparation of many cyclobutanes, presumably due to the instability of the cationic end of the initial zwitterion from this cyclic ketene acetal relative to those from acyclic ketene acetals.
Introduction Thermal reactions of the electron-rich donor alkenes D with electron-poor acceptor alkenes A usually lead to cyclobutanes 2 via intermediate zwitterions 1, as shown in Scheme 1.1-4 However, in certain cases cyclohexanes of the types 2A:1D (3, via zwitterion 5) and 2D:1A (4, via zwitterion 6) resulting from two molecules of one component and one of the other have been reported. Acyclic products from the trapping of zwitterion 1 with water or ethanol, such as 7, are also sometimes found. The formation of the cyclobutanes 2 cannot be a concerted 2s + 2s process according to the Woodward-Hoffmann rules. The zwitterion intermediate 1 in the 1:1 cycloadditions has to be sufficiently stabilized to allow the cyclobutane 2 to form, but if it is too stable, the ring can reopen to it, leading to other products. Thus, the ion-stabilizing substituents on the reacting alkenes have a major impact on the reaction pathway. Most donor alkenes used in 1:1 cycloadditions have been monosubstituted, such as vinyl ethers, styrene, p-methoxystyrene, and N-vinylcarbazole. A second donor substituent, such as in ketene diethyl acetal (8) and 2-methylene-1,3-dioxepane (9), the donor alkenes used in this study, leads to new effects based on their increased stabilization of the cationic end of the intermediate zwitterion 1 and their increased bulk. In our reactions of the ketene acetals 8 and 9 with alkenes containing from two to four carboalkoxyl and/or cyano groups, we obtained cyclobutanes 2 (our desired products), 2A:1D cyclohexanes 3, and acyclic products 7 from the trapping of the zwitterion 1 with water and ethanol. In this paper, we attempt to clarify the structural features and mechanisms that differentiate the reaction pathway to form either cyclobutanes 2, cyclohexanes 3 and 4, or acyclic products 7. * Author to whom correspondence should be addressed. † Part of the Langmuir special issue dedicated to the memory of David O’Brien: a superb scientist, valued colleague, and dear friend. (1) Seebach, D. In Houben-Weyl Methoden der Organischen Chemie, 4th ed.; Muller, Ed.; G. Thieme Verlag, Stuttgart: New York, 1971; Vol. IV, p 277. (2) Amice, P.; Conia, J. M. Bull. Soc. Chim. Fr. 1974, 1015. (3) Ooms, P. H. J.; Scheeren, J. W.; Nivard, R. J. F. Synthesis 1975, 260. (4) Scheeren, H. W.; van Rossum, A. J. R.; Nivard, R. J. F. Tetrahedron 1983, 39, 1345.
Scheme 1
Our interpretation in terms of the alkene polymerizability, zwitterion stabilization, and gem-dialkyl cyclization effects is then extended to other electron-rich alkenes.
Results We first consider the reactions of donor alkenes with geminal alkoxyl substituents, that is, ketene acetals, with alkenes with one-four acceptor substituents, in particular carboalkoxyl and cyano groups. Some pertinent literature results and the results of this study are listed in Table 1 according to the number and arrangement of electronwithdrawing groups (A) in the electron-poor alkene. Monosubstituted Acceptor Alkenes. For a zwitterionic 1:1 cycloaddition to occur between donor and acceptor alkenes, a sufficient polarity difference must exist between the two. If monosubstituted acceptor alkenes are used, the donor alkene must be highly reactive. Acrylonitrile and methyl acrylate do not react with vinyl ethers but do react with 8 (reactions 1 and 2) to form
10.1021/la027063a CCC: $25.00 © 2003 American Chemical Society Published on Web 05/02/2003
Electrophilic Alkenes
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Table 1. Reactions of Ketene Acetals with the Electron-Poor Alkenes R1R2CdCR3R4 ene A groups mono 1,1-di
1,2-di
tri
tetra
a
reaction
R1
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28
CN CO2Me CN CN CN CN CN CN CN CN CO2Et CO2Et CO2Et H H CN CN CN CN CO2Me CO2Me CO2Me CN CN CN CN CO2Et CO2Et
R2
R3
H H H H CN H CN C6H5 CN C6H5 CN C6H5 CN tBu CO2Me H H CN H CN H CO2Et H CO2Et CO2Et CH3 OdCsOsCdO OdCsOsCdO CN CO2Me CN CO2Me CN CO2Me CN CO2Me CN CO2Me CO2Me CO2Me CO2Me CO2Me CN CN CN CN CO2Me CN CO2Me CN CO2Et CO2Et CO2Et CO2Et
R4
ketene acetal
reference
solvent
cyclobutane (%)
cyclohexane (%)
H H H H H H H H H H H H H H H H H H H H H H CN CN CO2Me CO2Me CO2Et CO2Et
8 8 8 a a a a 8 8 9 8 9 9 8 9 8 8 8 9 9 8 9 8 9 8 9 8 9
5 5 6 4 4 4 7 b b b 8 b b 9 b b b b b b b b b b b b b b
t-BuOH CH3CN CH2Cl2 THF THF/H2O CH3CN Et2O CH3CN CH3CN CH3CN t-BuOH CH3CN CH3CN Et2O CH3CN CH3CN Et2O THF/TFA CH3CN CH3CN CH3CN CH3CN Et2O Et2O CH3CN CH3CN CH3CN CH3CN
10a (60) 10b (45) 0 10c (75) 0 0 10d (45) 0 0 0 10e (55) 0 0 0 0 0 0 0 16a (95) 16b (70) 0 16c (90) 0 16d (85) 10f (5) 16e (80) 0 0
0 0 11a (45) 0 0 11b (85) 0 11c (85) 0 0 0 0 0 14 (70) 0 11d (90) 0 0 0 0 11e (20) 0 0 0 0 0 0 0
open ester (%)
12a (high)
12b (90) 12b (40)c 12c (80)
Ketene dimethyl acetal. b This work. c Plus 60% ortho ester 15.
cyclobutanes 10a,b, as we recently showed.5 9 gave mostly polymeric products, apparently because the cycloadditions were quite slow.
1,1-Disubstituted Acceptor Alkenes. Vinylidene cyanide is the most reactive 1,1-disubstituted acceptor alkene. Stille and Chung (reaction 3) obtained the 2A:1D product 11a from the reaction of 8 with vinylidene cyanide.6 Higher yields were produced in more polar solvents, and the yield remained constant at 45% regardless of the donor/acceptor alkene ratio. Scheeren et al. studied the reactions of ketene dimethyl acetal with 2-phenylvinylidene cyanide, which is also highly reactive.4 In tetrahydrofuran (THF; reaction 4), he obtained a good yield of the cyclobutane 10c. When 10 equiv of water were added, the acyclic ester 12a was obtained instead, proving the existence of the intermediate zwitterion 1 (reaction 5). In the more polar solvent acetonitrile, which should stabilize the zwitterion 1, the 2A:1D cyclohexane 11b was obtained instead in excellent yield (reaction 6). Similarly, Polansky et al. reported the 1:1 cycloaddition of 8 with 2-tert-butylvinylidene cyanide to give the cyclobutane 10d in moderate yield (reaction 7).7 (5) Kniep, C. S.; Padias, A. B.; Hall, H. K., Jr. Tetrahedron 2000, 56, 4279. (6) Stille, J. K.; Chung, D. C. Macromolecules 1975, 8, 114.
We found 8 with methyl 2-cyanoacrylate (reaction 8) to give the crystalline cis 2A:1D cyclohexane 11c in high yield and its trans isomer as a minor product. The stereochemical assignments were based on the much larger difference between the chemical shifts for the two protons in the isolated methylene group in the 1H NMR spectrum of the major isomer. 1,2-Disubstituted Acceptor Alkenes. The 1,2-disubstituted acceptor alkenes are known to be much less reactive than the 1,1-disubstituted acceptor alkenes because they have a decreased ability to stabilize the anionic end of the zwitterion 1 and suffer from increased steric hindrance in the formation of the zwitterion 1. We could not find any cycloadducts from the reaction of either 8 or 9 with fumaronitrile (reactions 9 and 10). Bisacchi et al. isolated the cyclobutane 10e from the reaction of 8 with diethyl fumarate (reaction 11) and used it in the synthesis of antiviral drugs.8 In contrast, we did not obtain a cycloadduct from 9 and diethyl fumarate or diethyl methylfumarate (reactions 12 and 13). A 2D:1A cycloadduct (type 4, not 3) was reported as early as 1942 by McElvain and Cohen (reaction 14).9 In ether, maleic anhydride reacted with 2 equiv of 8 to give the cyclohexane 13, not isolated because under the reaction conditions it lost two ethanol molecules to form the anhydride 14. On the other hand, we found no cycloadduct from the reaction of maleic anhydride with 9 in acetonitrile (reaction 15). Trisubstituted Acceptor Alkenes. Because alkenes with three acceptor substituents readily react at room temperature with monosubstituted donor alkenes such (7) Bitter, J.; Leitich, J.; Partale, H.; Polansky, O. E.; Riemer, W.; Ritter-Thomas, U.; Schlamann, B.; Stilkerieg, B. Chem. Ber. 1980, 113, 1020. (8) Bisacchi, G. S.; Braitman, A.; Cianci, C. W.; Clark, J. M.; Field, A. K.; Hagan, M. E.; Hockstein, D. R.; Malley, M. F.; Mitt, T.; Slusarchyk, W. A.; Sundeen, J. E.; Terry, B. J.; Toumari, A. V.; Weaver, E. R.; Young, M. G.; Zahler, R. J. Med. Chem. 1991, 34, 1415. (9) McElvain, S. M.; Cohen, D. C. J. Am. Chem. Soc. 1942, 64, 260.
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as vinyl ethers and p-methoxystyrene,10 it was not surprising that these acceptor alkenes readily reacted with the ketene acetals 8 and 9. However, the reaction of 8 with alkenes containing three CN or CO2Me groups (reactions 16-18 and 21) gave no cyclobutanes, even though the solvent polarity, temperature, and reactant ratios were varied to try to facilitate cyclobutane formation. With 8 in the polar solvent acetonitrile, both methyl 3,3dicyanoacrylate and trimethyl ethylenetricarboxylate gave cyclohexane adducts (11d, reaction 16; 11e, reaction 21, respectively) with the latter reaction giving mainly the open ester 12c. In the case of methyl 3,3-dicyanoacrylate, the open ester 12b was formed in excellent yield in the less-polar solvent ether (reaction 17), whereas in THF containing trifluoroacetic acid (reaction 18), the products were the open ester 12b and ortho ester 15. In very strong contrast with the behavior of 8, the reactions of 9 with the same types of alkenes in acetonitrile (reactions 19, 20, and 22) gave high yields of the cyclobutane adducts 16a-c. Tetrasubstituted Acceptor Alkenes. Acceptor alkenes with four electron-withdrawing substituents have a wide variety of reactivity, from the highly reactive tetracyanoethylene to the very unreactive tetramethyl ethylenetetracarboxylate. Three alkenes were investigated: tetracyanoethylene, dimethyl dicyanofumarate, and tetramethyl ethylenetetracarboxylate. Of the three reactions of 8 with these alkenes (reactions 23, 25, and 27), a cycloadduct (cyclobutane 10f, in very low yield) was detected only for the reaction with dimethyl dicyanofumarate. In sharp contrast, the cyclic ketene acetal 9 gave cyclobutanes 16d,e in high yield in reactions with tetracyanoethylene and dimethyl dicyanofumarate, respectively (reactions 24 and 26). Even with the more reactive cyclic ketene acetal 9, the cyclobutane yield dropped to zero with the sterically hindered starting tetraester tetramethyl ethylenetetracarboxylate (reaction 28). Discussion Cyclobutanes 2. Even though all five types of electronpoor alkenes in Table 1 can be induced to form moderateto-excellent yields of the cyclobutanes 10 and 16 in reactions with ketene acetals, it is striking that the yields of cyclobutanes for alkenes tri- and tetrasubstituted with electron-withdrawing groups were much higher with the cyclic ketene acetal 9 than those with 8, and 9 should, thus, be preferred for the synthesis of these types of cyclobutanes. This difference can be rationalized from the much lower stability of the cationic end of the initial zwitterion 1 when the cyclic ketene acetal 9 is used: examination of molecular models shows that the cyclic cation can readily achieve significant resonance stabilization from only one oxygen rather than two for the acyclic cation. This favors rapid closure to the cyclobutane adduct 2 and also reduces the subsequent cyclobutane ring opening back to the zwitterion 1, which occurs with many cyclobutanes derived from acyclic ketene acetals.4 (10) Hall, H. K., Jr.; Padias, A. B. Acc. Chem. Res. 1997, 30, 322.
Johnston et al.
2A:1D Cyclohexanes 3. This type of 2:1 adduct can occur only when the electron-poor alkene is susceptible to anionic polymerization. Because all of the electron-poor alkenes in Table 1 except the tetrasubstituted ones can be polymerized anionically, this type of adduct was a possibility in all but the last six reactions. However, as is seen in Table 1, the 2D:1A cycloadducts 11 (and open esters 12, also obtained from the long-lived zwitterions 1) were found only in cases with alkenes 1,1-di- and trisubstituted with electron-withdrawing groups. Brannock et al.11 first noted that to obtain a cyclohexane 3 or 4, there must be sufficient stabilization of the ionic centers in the initial zwitterion 1 to allow reaction with another molecule of alkene before collapse to form a cyclobutane 2. Thus, the zwitterions 1 from alkenes mono- and 1,2disubstituted with electron-withdrawing groups, which have only one electron-withdrawing group stabilizing the anionic end of the zwitterion 1, do not generally exist long enough to produce 2:1 adducts. Another factor favoring cyclohexanes, noted by Stille and Chung,6 is that steric factors may hinder the closure of a four-membered ring. For example, in reaction 3 of 8 with vinylidene cyanide, the eclipsing that takes place in the transition state 17 leading to the cyclobutane 2 is avoided in the transition state 18, giving the observed cyclohexane 11a.
Scheeren et al.4 noted that the symmetrically substituted tetramethoxyethylene in reactions with electronpoor alkenes always yielded the cyclobutanes 2, whereas unsymmetrically substituted ketene acetals such as ketene dimethyl acetal yielded the cyclohexanes 3. They theorized that the nature of the products for the reaction of ketene acetals is strongly determined by the π-electron distribution in the ketene acetal and to a lesser extent by that in the electrophilic alkene. They suggested that the approach with the reactants starting their interaction in a trans arrangement (19) is preferred by the ketene acetals. The developing charges are far apart, and rotation around the primary formed C-C bond into a cis conformation is necessary for the completion of the cyclobutane formation. This allows the trapping of the zwitterion 1 by another alkene, leading to the cyclohexanes 3 and 4, or by water, leading to acyclic products, such as 7. With symmetrically substituted electron-rich alkenes such as tetramethoxyethylene, the approach geometry 20 leads to the cyclobutanes 2. We prefer another explanation consistent with a more expected (on grounds of attraction of opposite charges) cisoid-gauche approach of the reactants (21): the alkenes tetrasubstituted with electron-donating groups do not undergo anionic polymerization or oligomerization, and for the same reasons, the 4-type of 2:1 adduct should not be expected from them. The two β-alkoxyl substituents in the zwitterion 1 from tetramethoxyethylene inductively destabilize the cationic end, favoring the rapid closure to the cyclobutanes 2. Also, the alkoxyl or alkyl groups at the β position can exert the well-known “gem-dialkyl effect”, a steric effect favoring cyclization. Jung et al. has shown that β,β-dialkoxyl substitution, such as in the (11) Brannock, K. C.; Bell, A.; Burpitt, R. D.; Kelly, C. A. J. Org. Chem. 1964, 29, 801.
Electrophilic Alkenes
Langmuir, Vol. 19, No. 16, 2003 6419 Table 2. Reactions of Enamines with Electron-Poor Alkenes R1R2CdCR3R4
ene A groups
reaction
R1
R2
R3
R4
enamine
reference
solvent
cyclobutane (%)
cyclohexane (%)
1,1-di
29 30 31 32 33 34 35 36
CN CN CO2Et CN CO2Me CO2Me CN CN
CN CN CO2Et CN CO2Me CO2Me CN CN
C6H5 C6H5 H CN CO2Me CO2Me CN CN
H H H H H H CN CN
22 23 24 24 24 25 26 26
15 15 11 16 16 17 12 12
ether ether none toluene ether pentane CH2Cl2a CH2Cl2b
27a (35) 0 0 0 27b (100) 0 27c (100) 0
0 28 (85) 29a (80) 30 (30) 0 31a (5) 0 31b (85)
tri tetra a
30 s. b 7 h.
zwitterions from tetramethoxyethylene, strongly favors cyclobutane formation.12-14 The rates of the reactions in Table 1 increased monotonically as the number of acceptor groups went from one to four, with the cyano groups being more reactive. Tetracyanoethylene was the most reactive acceptor alkene. In contrast, the reactivity of the alkoxylsubstituted alkenes is at a maximum with the 1,1-disubstituted cases (with ketene acetals such as 8) and then becomes lower with tri- and tetramethoxyethylene.4 The reason for this difference is that for alkoxyl groups inductive and resonance effects work oppositely but for cyano groups they work in the same direction. One methoxyl group on a double bond stabilizes the initial zwitterion 1. A second alkoxyl group at the 1 position, such as in the ketene acetals, provides greater stabilization. A third alkoxyl group, however, slows the reaction because of the inductive rate-retarding effect of the β oxygen (and perhaps some steric effect as well). Similarly, a fourth methoxyl group gives drastic rate retardation. 2D:1A Cyclohexanes 4. This type of 2:1 adduct can occur whenever the electron-rich alkene is susceptible to cationic polymerization. Because the ketene acetals 8 and 9 used in this study are very readily polymerized cationically, this type of adduct was a possibility in all of the reactions yet was surprisingly noted only in reaction 14. This may reflect the greater stability of filled-shell stabilized carbanions over that of coordinatively unsaturated oxacarbenium ions. Enamines as Electron-Rich Alkenes. Parallel results have been found for cycloadditions with enamines as the electron-rich alkenes because all three types of the cycloadducts 2-4 are also observed with enamines (Table 2).
Polansky et al. (reaction 29) produced a 1:1 cycloadduct 27a from N-isobutenylmorpholine (22) and phenylvinylidene cyanide.15 In contrast, when N-(1-cyclohexenyl)morpholine (23) was the enamine (reaction 30), a 2A:1D (12) Jungf, M. E.; Kiankarimi, M. J. Org. Chem. 1995, 60, 7013. (13) Jung, M. E.; Marquez, R.; Houk, K. N. Tetrahedron Lett. 1999, 40, 2661. (14) Jung, M. E.; Marquez, R. Tetrahedron Lett. 1997, 38, 6521.
(3) cycloadduct 28 was formed in excellent yield. This difference can be rationalized on the basis of the higher stability of the tertiary carbon at the cationic end of the zwitterion 1 from the enamine 23 versus the secondary carbon from the enamine 22, with some additional driving force for the cyclobutane formation coming from the gemdimethyl groups in the zwitterion 1 from the enamine 22. Moreover, these cycloadditions rarely result in a bicyclic system involving a cyclobutane component. Another 1,1-disubstituted acceptor alkene, diethyl methylenemalonate, with N,N-dimethylisobutenylamine (24) also produced in high yield a 2A:1D cyclohexane adduct, 29a (reaction 31).11 The reactions of the trisubstituted acceptor alkenes tricyanoethylene and trimethyl ethylenetricarboxylate with enamines have been investigated. The highly electrophilic alkene tricyanoethylene reacted almost explosively with N,N-dimethylisobutenylamine (24, reaction 32), giving the cyclohexene 30 via the elimination of HCN from the 2A:1D cyclohexane adduct 29b.16 In contrast, the much less electrophilic trimethyl ethylenetricarboxylate with N,N-dimethylisobutenylamine (24, reaction 33) smoothly gave the cyclobutane adduct 27b in quantitative yield.16 Trimethyl ethylenetricarboxylate with N,N-dimethylvinylamine (25, reaction 34) apparently gave an unstable cyclobutane at low temperatures;16 a stable 2D: 1A adduct 31a was isolated in poor yield.17 In the reaction of N-vinylcarbazole (26) with tetracyanoethylene,12 the cyclobutane 27c formed initially (reaction 35); left at room temperature, a 2D:1A cyclohexane 31b and poly(vinylcarbazole) were obtained (reaction 36), showing the reversibility of the formation of the cyclobutane 27c. These results are consistent with the cationic polymerizability of N,N-dimethylvinylamine (25) and N-vinylcarbazole (26) and the anionic polymerizability or oligomerizability of phenylvinylidene cyanide, diethyl methylenemalonate, and tricyanoethylene. In the cases where polymerization is possible, cyclohexane adducts containing two units of the polymerizable entity may be formed. Ketone and Ester Anions as Electron-Rich Alkenes. This discussion can be further extended to enolate anions as electron-rich alkenes. Here, the 2A:1D reactions are greatly favored.18,19 With the ketone enolates (Scheme 2), the reactions can be considered to be MichaelMichael-aldol or anionic polymerization interrupted by aldol condensation to give cyclohexanols. With the ester enolates (Scheme 3), the reactions can be considered to be Michael-Michael-Claisen or anionic polymerization in(15) Penades, S.; Kisch, H.; Tortchanoff, K.; Margaretha, P.; Polansky, O. E. Monatsh. Chem. 1973, 104, 447. (16) Hall, H. K., Jr.; Ykman, P. J. Am. Chem. Soc. 1975, 97, 800. (17) Hall, H. K., Jr.; Abdelkader, M.; Glogowski, M. E. J. Org. Chem. 1982, 47, 3691. (18) Posner, G. H.; Lu, S. B.; Asirvatham, E.; Silversmith, E. F.; Shulman, E. M. J. Am. Chem. Soc. 1986, 108, 511. (19) Posner, G. H. Chem. Rev. 1986, 86, 831.
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Johnston et al.
Scheme 2
Scheme 3
Table 3. Correlation of the 2:1 Adducts 3 and 4 with Ionic Oligo- or Polymerizability of the Monomers ionic oligoor polymerizability
a
of D
of A
product
reaction
+
+
+
+ -
2A:1D (3) 2D:1A (4) 2A:1D (3) 2D:1A (4)
3,6 6,4 8,a 16a 149 21,a 30,15 31,11 3216 34,17 3612
This work.
terrupted by Claisen condensation to give cyclohexanones. The electron-poor alkenes used were anionically polymerizable acrylates. The cyclobutanes were not observed, although they can be made the major products by first silylating the enolates, as is shown by Ihara et al.20 Summary The reactions above, which give the 2:1 adducts 3 and 4, are listed in Table 3 according to the ionic homopolymerizability of their reaction components. As is expected, an extra donor alkene is added only if the donor alkene is anionically oligomerizable or polymerizable, and an extra acceptor alkene is added only if the acceptor alkene is cationically oligomerizable or polymerizable. If both alkenes are homopolymerizable, the 2:1 adduct usually contains an extra acceptor alkene rather than a donor alkene. Experimental Section General Procedures. 1H NMR spectra were run at 200 MHz and 13C NMR spectra at 50 MHz on a Varian Gemini-200 spectrometer in deuteriochloroform. Mass spectra were run on a JEOL HX110A spectrometer. General Cycloaddition Procedure. An electron-rich alkene was mixed with 1 equiv of 8 or 9 in acetonitrile (or another solvent as specified) at 25 °C and stirred until the disappearance of the color of the charge complex occurred. In some cases of very electron-rich alkenes, reaction occurred at -78 °C in ether solvents, and for some relatively unreactive electron-rich alkenes, heating to reflux was employed. The solvent was evaporated on a rotary evaporator, and the products were analyzed by NMR spectroscopy, mass spectroscopy (MS), and IR spectroscopy. The solid products were separated by filtration, which was sometimes followed by washing and recrystallization. 8 with Methyl 2-Cyanoacrylate (Reaction 8). The reaction was conducted at 25 °C in acetonitrile for 2 days. After solvent evaporation under reduced pressure, the residue partially crystallized. Several washings with ether yielded 65% of the pure crystalline cis 2:1 cycloadduct 11c. IR (NaCl, neat): 2989, 2257, 1736, 1444 cm-1. 1H NMR: δ 4.2-4.3 (m, 1H), 3.85 (s, 3H), 3.83 (s, 3H), 3.6-3.7 (m, 3H), 3.04 (d, J ) 15 Hz, 1H), 2.57 (d, J ) 15 Hz, 1H), 2.42 (m, 1H), 2.05-2.15 (m, 3H), 1.32 (t, J ) 7 Hz, 3H), 1.29 (t, J ) 7 Hz, 3H). FABMS m/z: 339 [M + 1]+. A pair of (20) Ihara, M.; Taniguchi, T.; Makita, K.; Takano, M.; Ohnishi, M.; Taniguchi, N.; Fukumoto, K.; Kabuto, C. J. Am. Chem. Soc. 1993, 115, 8107.
doublets at δ 2.77 and 2.87 (J ) 15 Hz) in the 1H NMR spectrum of the initial product mixture showed the trans 2:1 adduct to be present in a smaller quantity (ca. 20%). 8 with Diethyl Fumarate (Reaction 11). The cyclobutane 10e was prepared by the literature method.8 1H NMR: δ 4.1-4.2 (m, 2H), 4.11 (q, J ) 7 Hz, 2H), 3.66 (dq, J ) 10, 7 Hz, 1H), 3.52 (dq, J ) 10, 7 Hz, 1H), 3.50 (br d, J ) 8 Hz, 1H), 3.37 (q, J ) 7 Hz, 2H), 3.28 (ddd, J ) 10, 9, 8 Hz, 1H), 2.54 (dd, J ) 12, 10 Hz, 1H), 2.18 (ddd, J ) 12, 9, 1 Hz, 1H), 1.22 (t, J ) 7 Hz, 3H), 1.21 (t, J ) 7 Hz, 3H), 1.16 (t, J ) 7 Hz, 3H), 1.08 (t, J ) 7 Hz, 3H). 13C NMR: δ 174.1, 169.5, 99.9, 61.3, 57.9, 57.2, 52.9, 34.8, 31.6, 15.4, 14.6. HRFABMS: [M + 1]+ calcd, 289.165; found, 289.166. 8 with Methyl 3,3-Dicyanoacrylate (Reactions 16-18). Reaction 16 occurred at 25 °C in acetonitrile. After the removal of the solvent, the 2:1 cycloadduct 11d was washed with ether several times to give a 90% yield. IR (NaCl, neat): 2989, 2256, 1759, 1739, 1450 cm-1. 1H NMR: δ 4.07 (s, 3H), 3.90 (s, 3H), 3.65-3.95 (m, 4H), 3.62 (s, 1H), 3.19 (dd, J ) 13, 3 Hz, 1H), 2.78 (dd, J ) 15, 3 Hz, 1H), 2.33 (dd, J ) 15, 13 Hz, 1H), 1.37 (t, J ) 7 Hz, 3H), 1.35 (t, J ) 7 Hz, 3H). HRFABMS: [M + 1]+ calcd, 389.149; found, 389.147. Reaction 17 was run in diethyl ether at -78 °C, giving the diester 12b in 90% yield. IR (NaCl, neat): 1759, 1739 cm-1. 1H NMR: δ 4.54 (d, J ) 6.5 Hz, 1H), 4.18 (q, J ) 7 Hz, 2H), 3.82 (s, 3H), 3.47 (q, J ) 6.5 Hz, 1H), 3.00 (dd, J ) 16, 6 Hz, 1H), 2.85 (dd, J ) 16, 7 Hz, 1H), 1.26 (t, J ) 7 Hz, 3H). 13C NMR: δ 169.6, 168.6, 111.3, 111.1, 61.8, 53.4, 41.7 (CHCd O), 33.0, 23.8 (CH(CN)2), 13.9. After reaction 18, in THF containing 1 equiv of trifluoroacetic acid, the 1H NMR spectrum showed the products to be the ortho ester 15 (60%) and diester 12b (40%). 1H NMR: δ 4.60 (d, J ) 6 Hz, 1H), 3.81 (s, 3H), 3.55 (q, J ) 7 Hz, 6H), 3.23 (ddd, J ) 10, 6, 4 Hz, 1H), 2.36 (dd, J ) 14, 4 Hz, 1H), 2.17 (dd, J ) 14, 10 Hz, 1H), 1.17 (t, J ) 7 Hz, 9H). 9 with Methyl 3,3-Dicyanoacrylate (Reaction 19). The reaction occurred at 25 °C in acetonitrile. After the removal of the solvent, the 1H NMR and mass spectra indicated the 1:1 adduct 16a to be the major product (95%). IR (NaCl, neat): 2980, 2243, 1735, 1440 cm-1. 1H NMR: δ 3.7-4.0 (m, 4H), 3.85 (s, 3H), 3.52 (t, J ) 8 Hz, 1H), 2.84 (dd, J ) 14, 9 Hz, 1H), 2.65 (dd, J ) 14, 8 Hz, 1H), 1.6-1.8 (m, 4H). FABMS m/z: 251 [M + 1]+. 9 with Dimethyl 2-Cyanofumarate (Reaction 20). The reaction occurred at 25 °C in acetonitrile. After the removal of the solvent, the 1H NMR spectrum indicated the major cycloaddition product (60%) to be the 1:1 adduct 16b. 1H NMR: δ 3.5-3.85 (m, 4H), 3.84 (s, 3H), 3.75 (s, 3H), 3.31 (dd, J ) 7, 5 Hz, 1H), 2.57 (dd, J ) 14, 5 Hz, 1H), 2.08 (dd, J ) 14, 7 Hz, 1H), 1.65-1.75 (m, 4H). FABMS m/z: 251 [M + 1]+. 8 with Trimethyl Ethylenetricarboxylate (Reaction 21). The reaction was conducted at room temperature in acetonitrile and finished overnight. After the removal of the solvent, recrystallization from ether gave the tetraester 12c (80%). IR (NaCl, neat): 2987, 1738, 1434 cm-1. 1H NMR: δ 4.14 (q, 2H), 3.93 (d, J ) 6 Hz, 1H), 3.75 (s, 3H), 3.74 (s, 3H), 3.70 (s, 3H), 3.58 (dt, J ) 7, 6 Hz, 1H), 2.79 (dd, J ) 16, 7 Hz, 1H), 2.72 (dd, J ) 16, 6 Hz, 1H), 1.25 (t, J ) 7 Hz, 3H). 13C NMR: δ 172.0, 171.5, 167.6, 167.4, 61.0, 52.9, 52.6, 52.2, 40.5, 33.5, 14.0. The 1H NMR spectrum before crystallization indicated the other main product (20%) to be the 2:1 adduct 11e. 1H NMR: δ 3.7-4.0 (m, 24H), 2.86 (dd, J ) 17, 4 Hz, 1H), 2.51 (dd, J ) 17, 13 Hz, 1H), 1.35 (t, J ) 7 Hz, 6H). 9 with Trimethyl Ethylenetricarboxylate (Reaction 22). The reaction was conducted at 25 °C in acetonitrile and finished overnight. After the removal of the solvent, the 1H NMR and mass spectra showed the main product (90%) to be the 1:1 adduct 16c. 1H NMR: δ 3.6-3.9 (m, 4H), 3.86 (s, 3H), 3.68 (s, 6H), 2.49 (dd, J ) 14, 5 Hz, 1H), 2.08 (dd, J ) 14, 7 Hz, 1H), 1.6-1.7 (m, 4H). FABMS m/z: 317 [M + 1]+. 9 with Tetracyanoethylene (Reaction 24). The reaction was run at -78 °C in ether. The solvent was removed at -78 °C under reduced pressure to afford the 1:1 adduct 16d as a white powder (85%). IR (NaCl, neat): 2939, 1725, 1407 cm-1. 1H NMR: δ 4.03 (m, 2H), 3.89 (m, 2H), 3.30 (s, 2H), 1.87 (m, 2H), 1.83 (m, 2H). HRFABMS: [M + 1]+ calcd, 243.088; found, 243.088. 8 with Dimethyl trans-1,2-Dicyanoethylene-1,2-dicarboxylate (Reaction 25). The reaction occurred at 25 °C in acetonitrile to give mostly acyclic products, but a trace of the 1:1 adduct 10f (5%) was observed in the 1H NMR and mass spectra.
Electrophilic Alkenes
Langmuir, Vol. 19, No. 16, 2003 6421
1H NMR: δ 2.72 (d, J ) 15 Hz, 1H), 2.55 (d, J ) 15 Hz, 1H). FABMS m/z: 311 [M + 1]+.
66.3, 66.1, 59.8, 56.2, 55.1, 42.5, 35.8, 29.0, 28.9. FABMS m/z: 309 [M + 1]+.
9 with Dimethyl trans-1,2-Dicyanoethylene-1,2-dicarboxylate (Reaction 26). The reaction occurred at 25 °C in acetonitrile. After the removal of the solvent, the cyclobutane 16e was recrystallized from ether (80%). IR (NaCl, neat): 2985, 2259, 2209, 1746 cm-1. 1H NMR: δ 4.0-4.1 (m, 2H), 3.90 (s, 6H), 3.75 (m, 2H), 2.65 (d, J ) 15 Hz, 1H), 2.55 (d, J ) 15 Hz, 1H), 1.75-1.8 (m, 4H). 13C NMR: δ 166.7, 166.2, 117.1, 116.6, 115.8,
Acknowledgment. We are very grateful to the Materials Research Division of the National Science Foundation and the Petroleum Research Fund of the American Chemical Society for generous funding of this work. LA027063A
