J . Am. Chem. SOC.1988, 110, 3238-3246
3238
dideuteriocyclohexane (based on AIC12). Reaction of Bromobenzene with Aluminum and Aluminum Trichloride. Bromobenzene (22 mmol) was added to a slurry of aluminum dichloride (74 mmol obtained by AICI, + K) in xylene. After the solution was stirred for 10 h at 100 OC, the solvent was removed by vacuum and the slurry was quenched with 10% HCI. The GC analysis of the products showed benzene (55%) and unreacted bromobenzene (40%). Reaction of Dimethyl Ether with Aluminum and Aluminum Trichloride. Into a 200-mL Monel autoclave was charged the reaction product of aluminum trichloride ( I I O mmol) and aluminum (60 mmol) in 30 mL of xylene under argon. A total of 10 mL of dimethyl ether was then added at -30 OC;the vessel was closed and heated from 70 to 190 OC for 3 h. The autoclave was then cooled, and the product (obtained by hydrolysis) was analyzed by GC-MS showing methane (31%). methyl chloride (29%), and unreacted dimethyl ether (39%) with traces of ethane
and butane.
Acknowledgment. Support by the National Science Foundation is gratefully acknowledged. Prof. L. Dalton, C. Young, and P. H. Bryson are thanked for t h e ESR measurements. Registry No. 8 (X = CI), 59534-55-3; 9 (X = CI), 95465-40-0; 9 (X = Br), 113749-58-9; AICI,, 7446-70-0; AIBr,, 7727-15-3; CI,, 7782-50-5; A12CI4, 12330-29-9; AIC12, 16603-84-2; CH2=CH2, 74-85-1; CH3CH3, 74-84-0; CH3CH(HgC1)2, 32823-01-1; EtAICI,, 563-43-9; CH3C1, 7487-3; CH,AICI,, 917-65-7; C 0 2 , 124-38-9; Et3A1, 97-93-8; C6HsBr, 108-86-1; CH3OCH3, 115-10-6; CHI, 74-82-8; HgC12, 7487-94-7; HCI, 7647-01-0; Al*(i-Bu),, 60253-71-6; AICI, 13595-81-8; Et?AICI, 93-10-6; AI, 7429-90-5; K, 7440-09-7; methylmalonic acid, 5 16-05-2; cyclohexene, 110-83-8; cyclohexane, 110-82-7; sodium acetate, 127-09-3.
4-Oxazoline Route to Stabilized Azomethine Ylides. Controlled Reduction of Oxazolium Salts E. Vedejs* and J. W. Grissom Contributionfrom S . M . McEIvain Laboratory of Organic Chemistry, Department of Chemistry, University of Wisconsin, Madison, Wisconsin 53706. Receiced September 3, I987
Abstract: Treatment of oxazolium salts with phenylsilane/CsF generates 4-oxazolines 14 in situ. Provided that R, = H or alkoxy, ring opening to azomethine ylides 15 occurs spontaneously and [2 31 cycloadducts are obtained in the presence of acrylate, N-phenylmaleimide, propiolate, or dimethyl acetylenedicarboxylate (DMAD) dipolarophiles. If R, = alkyl or aryl, the initially formed 4-oxazoline resists ring opening, probably due to steric interactions in the dipole, and affords products 30 derived from 2 2 trapping with DMAD. In typical cases, the [2 + 31 cycloadducts are formed with geometry corresponding to the trapping of the S-dipole 15 to the exclusion of other dipole isomers. Pyrolysis of analogous N-methylaziridines results in an equilibrated dipole, although the major adduct also corresponds to the trapping of 15. Dipole trapping with phenyl vinyl sulfone is also possible, and reductive desulfonylation with sodium amalgam affords the adduct 41, which corresponds to the adduct of the stabilized azomethine ylide with ethylene. Overall, the oxazolium salt reduction provides access to a large variety of azomethine ylides stabilized by acyl, ester, benzoyl, and formyl substituents. The dipoles can be generated and trapped at room temperature or below.
+
+
Azomethine ylides have been extensively studied since the 1965 discovery that they can be generated by pyrolysis of aziridines. The reaction of 1,2,3-triphenylaziridinewith electron-deficient olefins or acetylenes to yield five-membered nitrogen rings was reported by Heine and Peavey,Ia and similar independent findings were described by Padwa and HamiltonIb and by Huisgen, Scheer, Szeimies, and Huber.lc Due to t h e systematic investigations by Huisgen et al., it is now well known that thermolysis of 1phenyl-2,3-dicarbomethoxyaziridineinvolves conrotatory ring opening to t h e carbonyl-stabilized ylides 3 or 4.* Trapping products of t h e S-dipole 3 are obtained from t h e cis aziridine 1, while adducts of t h e isomeric W-dipole 4 result from t h e trans aziridine 2. The S-dipole 3 is trapped by several dipolarophiles without loss of dipole geometry. In contrast, the W-dipole 4 reacts cleanly only with t h e most reactive of traps such as dimethyl acetylenedicarboxylate (DMAD). W i t h less reactive dipolarophiles ( f u m a r a t e and norbornene), products derived from the S-dipole 3 are also observed due to dipole interconversion. These topics have been extensively reviewed, and the concepts have been extended t o nonstabilized azomethine y l i d e ~ . ~ - ~ ~
(1) (a) Heine, H. W.; Peavy, R. E. Tetrahedron Lett. 1965, 3123. (b) Padwa, A.; Hamilton, L. Tetrahedron Left. 1965, 4363. (c) Huisgen, R.; Scheer, W.; Szeimies, G.; Huber, H. Tetrahedron Lerr. 1966, 397. (2) (a) Huisgen, R.; Mader, H. J . Am. Chem. SOC.1971, 93, 1777. (b) Huisgen, R. Scheer, W.; Huber, H. J . Am. Chem. Sac. 1967, 89, 1753. (3) (a) Lown, J. W. In 1,3-Dipolar Cycloaddition Chemisrry; Padwa, A,,
Ed.; Wiley: New York, 1984; Chapter 6. (b) Huisgen, R. In 1,3-Dipolar Cycloaddition Chemistry; Padwa, A., Ed.; Wiley: New York, 1984; Chapter 1.
(4) For a review of pyridinium ylides, see: Krohnke, F. Angew. Chem. 1953, 65, 617.
M a n y other examples of aziridine thermolysis have been reported in t h e literature.’w18 The mechanism of dipole trapping ( 5 ) (a) Vedejs, E.; West, F. G . Chem. Reo. 1986, 941. (b) Vedejs, E. In Aduances in Dipolar Cycloaddition Chemistry; Curran, D. Ed.; JAI:
Greenwich, CT, 1988. ( 6 ) (a) Lown, J. W. Rer. Chem. Prog. 1971, 32, 5 1 . (b) Huisgen, R. J . Org. Chem. 1968, 33,2291. (c) Stuckwisch, C. G. Synthesis 1973,469. (d) Kellogg, R. Tetrahedron 1976, 32, 2165. (7) Huisgen, R. Spec. Pu6l.-Chem. SOC.1970, No. 21; Ollis, B. Tetrahedron 1985, 41, 2239. (8) Vedejs, E.; Martinez, G. R. J . Am. Chem. Soc. 1979, 101, 6542. (9) Katritzky, A. R.; Dennis, N.; Chaillet, M.; Larrieu, C.; El Mouhtadi, M. J . Chem. Soc., Perkins Trans. 1 1979, 408. (IO) (a) Heine, H. W.; Smith, A. B., 111; Bower, J. D. J . Org. Chem. 1968, 33, 1097. (b) Padwa, A.; Hamilton, L. J. Heterocycl. Chem. 1967, 4, 118. (11) (a) Padwa, A.; Eisenhardt. W. J . Org. Chem. 1970, 35, 2472. (b) Hiyama, T.; Taguchi, H.; Nozaki, H. Bull. Chem. SOC.Jpn. 1974.47, 2909. (12) Heine, H. W.; Peavy, R.; Durbetaki, A. J. J . Org. Chem. 1966, 31, 3924. (13) (a) Huisgen, R. Hela. Chim. Acto 1967, 50, 2421. (b) Hall, J. H.; Huisgen, R. J . Chem. SOC.,Chem. Commun. 1971, 1187. (c) Hall, J. H.; Huisgen, R.; Ross, C. H.; Scheer, W. J . Chem. SOC.,Chem. Commun. 1971, 1188. (d) Huisgen, R.; Scheer, W.; Mader, H. Angew. Chem., Int. Ed. Engl. 1969,8, 602; Huisgen, R.; Scheer, W.; Mader, H.; Brunn, E. Angew. Chem., Int. Ed. Engl. 1969, 8, 604. (14) (a) Texier, F.; Carrie, R. Bull. SOC.Chim. Fr. 1971, 4119. (b) Bastide, J.; Hamelin, J.; Texier, F.; Quang, Y. V. Bull. SOC.Chim. Fr. 1973, 2871. (c) Deyrup, J. A. J . Org. Chem. 1969, 34, 2724. (d) Husinec, S.; Porter, A. E. A.; Roberts, J. S.; Strachan, C. H. J . Chem. SOC.,Perkin Trans. 1 1984, 2517. (15) (a) Woller, P. B.; Cromwell, N. H. J. Org. Chem. 1970, 35, 888. (b) Lown, J. W.; Akhtar, M. H. Can. J. Chem. 1972, 50, 2236. (16) (a) Padwa, A.; Ku, H. J . Org. Chem. 1979, 44, 255. (b) Wenkert, D.; Ferguson, S. B.; Porter, B.; Qvarnstrom, A.; McPhail, A. T. J . Org. Chem. 1985, 50, 41 14. (c) Vedejs, E.; Grissom, J. W.; Preston, J. K. J . Org. Chem. 1987, 52, 3487.
0002-7863/88/1510-3238$01.50/00 1988 American Chemical Society
J . Am. Chem. SOC.,Vol. 110, No. 10, 1988 3239
4 - Oxazoline Route to Stabilized Azomethine Ylides
13
14
(DMAD)
r
1
LE'
9
15
1 y ' s
19a
12 22
Figure 1.
23
24
They have been generated from the thermolysis of aziridines, but is generally described as an asynchronous c y c l ~ a d d i t i o nal,~~~~~ the resulting ylides undergo proton transfer and intramolecular though alternative interpretations have been proposed.I9 The cyclization a t the elevated temperatures required for their forN-arylaziridines have been investigated most inten~ively,'~-'~ but mati~n.~'-~~ N-alkyl,'s-18 N-H,l0 and N-acyl" derivatives have also been enA possible low-temperature alternative to the methods outlined countered. Other routes to stabilized azomethines include the above could involve the generation of an acyl-stabilized azomethine thermolysis of benzaldimines,21 the related method of thermal ylide from the valence bond tautomer 4-oxazoline. An example N-alkylamino ester/aldehyde c o n d e n s a t i ~ n , ~iminium ~ * ~ ~ salt of the reverse reaction has been encountered in a study by Baldwin deprotonation or de~ilylation,~J~ or carbene insertion into an imine et al. (Figure l).30 The aziridine 7 (formed from the cycloadduct nitrogen lone pair.26 6 between nitrone 5 and DMAD) is converted into the stable While many of these techniques are synthetically useful, most 4-oxazoline 8 upon further heating. Presumably, the rearsuffer from some limitations. In particular, stabilized ylides that rangement involves an intermediate azomethine ylide. There is are substituted by an "enolizable" alkyl group can be troublesome. also a realted example where the formation of 4-oxazoline 10 from the pyrolysis of aziridine 9 is indicated by the isolation of the [2 21 DMAD adduct 11 and its thermal rearrangement product (17) DeShong, P.; Kell, D. A,; Sidler, D. R. J. Org. Chem. 1985,50, 2309. 12.16cThe intermediate azomethine ylide in this case does not (18) Gelas-Mialhe, Y.; Hierle, R.; Vessiere, R. Bull. Soc. Chim. Fr. 1974, 709. react by [2 31 cycloaddition with DMAD. In an earlier study, (19) (a) Firestone, R. J . Org. Chem. 1968, 33, 2285. (b) Firestone, R. Texier et al. have obtained a 4-oxazoline from the thermolysis Tetrahedron 1977, 33, 3009. of a 5-a~yltriazoline.'~~ Further heating of the oxazoline in the (20) (a) Houk, K. N.; Sims, J. J . Am. Chem. Soc. 1973, 95, 5798. (b) presence of DMAD affords a pyrroline via the azomethine ylide. Houk, K. N.; Sims, J.; Duke, R. E.; Stozier, R. W.; George, J. K. J. Am. Chem. SOC.1973,95,7287. (c) Houk, K. N.; Sims, J.; Watts, C. R.; Luskus, This is the only prior example where a 4-oxazoline has been shown L.J. J . Am. Chem. SOC.1973,95,7301. (d) Imai, N.; Tokiwa, H.; Akahori, to give azomethine ylide trapping products, although 4-oxazolines Y.; Achiwa, K. Chem. Lett. 1986, 11 13. have been isolated in other s t ~ d i e s . ~ ~ , ~ ~ (21) (a) Joucla, M.; Hamelin, J. TetrahedronLett. 1978,2885. (b) Grigg,
+
+
R. Bull. SOC.Chim. Belg. 1984,93,593. (c) Tsuge, 0.;Ueno, K.; Kanemasa, S.; Yorozu, K. Bull. Chem. Sac. Jpn. 1986,59, 1809. (d) Joucla, M.; Fouchet, B.; Hamelin, J. Tetrahedron 1985, 41, 2707. (22) (a) Tsuge, 0.;Kanemasa, S.;Obe, M.; Yorozu, K.; Takenaka, S.; Ueno, K. Chem. L e f f .1986, 1271. (b) Tsuge, 0.; Kanemasa, S.; Ohe, M.; Takenaka, S. Chem. Lett. 1986, 973. (c) Joucla, M.; Mortier, J. J . Chem. Soc., Chem. Commun.1985, 1566. (d) Joucla, M.; Mortier, J.; Hamelin, J. Tetrahedron Lett. 1985, 26, 2775. (23) (a) Tsuge, 0.;Ueno,K. Heterocycles 1983,20, 2133. (b) Armstrong, P.; Grigg, R.; Jordan, M.; Malone, J. F. Tetrahedron 1985, 41, 3547. (c) Confalone, P.; Earl, R. A. Tetrahedron Lett. 1986, 27, 2695. (24) (a) Huisgen, R.; Grashey, R.; Steingruber, E. TetrahedronLett. 1963, 1441. (b) Deyrup, J.; Szabo,W. A. J. Org. Chem. 1975,40,2048. (c) Kraus, G.; Nagy, J. 0. Tetrahedron 1985.41, 3537. (d) Imai, N.; Terao, Y.; Achiwa, K. Heterocycles 1986, 24, 267. (25) Vedejs, E.; Dax, S.; Martinez, G. R.; McClure, C. K. J . Org. Chem. 1987, 52, 3470. (26) Bartnik, R.; Mloston, G. Tetrahedron 1984, 40, 2569.
(27) (a) Achenson, R. M.; Bailey, A. S.; Selby, I. A. J . Chem. SOC.,Chem. Commun.1966, 835. (b) Schmidt, G.; Stracke, H.-U.; Winterfeldt, E. Chem. Ber. 1970,103, 3196. (c) Dowd, P.; Kang, K. J. Chem. SOC.,Chem. Commun. 1974, 258. (28) Padwa, A.; Dean, D.; Oine, T. J . Am. Chem. SOC.1975, 97, 2822. (29) Dopp, D.; Nour-El-Din, A. M. Tetrahedron Letr. 1978, 1463. (30) Baldwin, J. E.; Pudussery, R. G.; Qureshi, A. K.; Sklarz, B. J . Am. Chem. SOC.1968, 90, 5325. (31) (a) Vaultier, M.; Mullick, G.; Carrie, R. Can. J . Chem. 1979, 57, 2876. (b) Hunt, E.; Zomaya, I. I. J . Chem. SOC.,Perkin Trans. 1 1982, 1509. (c) Spry, D. 0. J . Org. Chem. 1975, 40, 2411. (32) (a) Kobayashi, Y.;Kumadaki, I.; Yoshida, T. Heferocycles 1977,8, 387. (b) Nour-El-Din, A. M.; Mourad, A,-F. E.&; Mekamer, R. Heterocycles 1985, 23, 1155. (c) Saunier, Y. M.; Danion-Bougot, R.; Danion, R.; Carrie, R. Tetrahedron 1976.32, 1995. (d) Lown, J. W.; Matsumoto, K. Can. J. Chem. 1972,50, 534.
3240 J . Am. Chem. SOC.,Vol. 110, No. 10, 1988 The relatively few stable 4-oxazolines cited in the literature are heavily substituted by electron-withdrawing groups, which stabilize the enamine double bond. It seemed likely that increasing the basicity of nitrogen by replacement of the stabilizing substituents by alkyl, phenyl, etc., would promote ring opening to the ylide. To test this proposition, a general method for synthesis of 4-oxazolines was required. This long-standing problem has been solved by the controlled reduction of oxazolium salts33 with the PhSiHJCsF reagent,34and the behavior of the resulting 4-oxazolines is the subject of this report.
Results Several factors influenced the ultimate choice of the reducing agent for conversion of oxazolium salts into 4-oxazolines. A nucleophilic hydride donor was required that would not affect the 4-oxazoline or the iminium portion of the azomethine ylide 15 or its isomers 16-18 (Figure 2). These limitations rule out protic conditions and reducing agents having Lewis acid character. In order for this approach to succeed, either the oxazoline 14 must be stable under the reaction conditions or the azomethine ylide generated must undergo [2 31 cycloaddition faster than it can be reduced. If the product oxazoline is stable, the dipolarophile need not be present during the reduction step and could be added later. However, if the oxazoline spontaneously opens to the ylide, the dipolarophile would have to be present throughout. In this case, the reducing agent would have to reduce the oxazolium salt 13 selectively while leaving the dipolarophile intact. All of these conditions are satisfied by the silane/CsF reagent. Treatment of N-methyl-2,5-diphenyloxazoliumsalt with sodium borohydride or with sodium cyanoborohydride under a variety of conditions produced N-methyl-N-phenacylbenzylamineas the major product. A similar experiment at room temperature with phenylsilane/cesium fluoride led to the same amine overreduction product (Scheme I) as before, indicating that ring opening of the 4-oxazoline 14a was rapid in all cases. However, when the reduction was carried out in the presence of DMAD in deuteriated acetonitrile, N M R analysis of the crude product revealed the presence of the trans 3-pyrroline 19s. The structure is clear from the large value ( J = 7.5 Hz) observed for the long-range H2-H5 coupling that is characteristic of this ring The issue of adduct stereochemistry will be discussed in the section dealing with dipole geometry. Attempts to purify the 3-pyrroline 19a were complicated by epimerization, double-bond isomerization, and aromatization, resulting in a mixture of 3-pyrrolines, 2-pyrrolines, and the pyrrole 20a. Therefore, treatment of the crude reaction mixture with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) was performed to convert all of the cycloadduct-derived structures into the pyrrole ma.To obtain supporting evidence for the structural assignments, the same pyrrole was also made by the aziridine method. Thus, (21)35at thermolysis of 1-methyl-cis-2-benzoyl-3-phenylaziridine 100 OC in the presence of DMAD yielded the 2-pyrrolines 22a (53%) and the pyrrole 20a (47%). All of these products had been observed in the attempted purification of 19a obtained via the oxazoline route. However, the sensitive 3-pyrroline 19a did not survive the high-temperature conditions for azomethine ylide formation from the aziridine. Due to the sensitivity of the initial adduct 19a, the DDQ aromatization procedure was used routinely in optimization experiments. Despite some gas evolution from the silane/CsF reagent in acetonitrile, this solvent proved to be superior to ethers or halocarbons. Of the various silane reducing agents that were tried, phenylsilane gave the cleanest reactions and the highest yields of pyrrole 2Oa (95%), although diphenylsilane (93%) and phenyldimethylsilane (60%) also led to the desired cycloadduct. No reduction was seen with tributyltin hydride in the absence of a catalyst, but both tributyltin hydride and triethoxysilane could
+
(33) Turchi, I. J. In Oxazoles; Turchi, I. J., Ed.; Wiley: New York, 1986; Chapter 1. (34) (a) Corriu, R. J. P.; Perz, R.; Reye, C. Tetrahedron 1983, 39, 999. (b) Vedejs, E.; Grissom, J. W. J. Am. Chem. SOC.1986, 108, 6433. (35) Cromwell, N. H.; Caughlin, J. J . Am. Chem. SOC.1945, 67, 2235.
Vedejs and Grissom Table I. Dimethyl Acetylenedicarboxylate Trapping of 14 entry R2 RS yield of 20, % a Ph Ph 95 b Ph OEt 90 C Ph Me 93 d Me Ph 85 e Me OEt 64 f H Ph 74 Table 11. Propionate Trapping of 14 Me
entry a b C
d e
f
R? Ph Ph Ph Me Me
H H
g
0
RS
R
Ph OEt Me Ph OEt Ph OEt
Et Et Et Me Et
Me
0
isolated '0 yields, 7
10 13 3 0 9 21 9
40 48 16
14 35 6 20
Et Me
Table 111. Acrylate Trapping of 14 %+
- b..,U(R5
2)PhSiHJ
CrFlacvlats
entry a b
R2 Ph
C
Ph Me Me
d e f
P F , . V p 5
1) MBOTI
R,
Ph
Me02d"
C0,Me
isolated yield, %
RS Ph OEt Me Ph
55 63 87 40
OEt
61 0 47" 57
g
H H
Ph OEt
h
Ph
H
9 10
0 20 0 67 0 0
" 1.35:l mixture of stereoisomers. act as marginally useful hydride donors in the presence of a fluoride source (
