[67609-52-3]  · C11H24O3Si2  · 1-Methoxy-1,3-bis(trimethylsilyloxy)-1,3-butadiene  · (MW 260.53) (E)

[74590-73-1] (Z)


(reactive diene for the Diels-Alder reaction;1,2 acetoacetic ester dianion equivalent that reacts with various electrophiles3)

Physical Data: bp 56-58 °C/2.0 mmHg.2

Solubility: insol H2O; sol most organic solvents.

Preparative Methods: from methyl acetoacetate according to the scheme shown in eq 1.2,3 A detailed experimental procedure is described by Chan et al.3c It is critical that the reaction temperature for the metalation step be less than -23 °C. Under these conditions, essentially pure diene is obtained, but at rt the reaction gives a 3:1 mixture of the diene and C-silylated products derived by rearrangement. The stereochemistry of the diene was first proposed to be (E),3a but later was shown to be (Z) by precise NMR studies.4

Handling, Storage, and Precautions: although this diene is purified safely by distillation below 80 °C,2,5 O- to C-migration of a silyloxy group is observed at elevated temperatures (see eq 2).3,5 Crude diene may be used directly without further purification and it can be kept in a stoppered container in a freezer for several weeks without appreciable decomposition. It is slowly hydrolyzed when exposed to air and moisture.3c

Thermal Rearrangement.

On being heated at 120 °C for 1 h, the diene (1) and related analogs rearrange to give C-silyl-(E)-a,b-unsaturated esters (eq 2).5 Flash vacuum pyrolysis of the diene at 680 °C gives an allene ester via concomitant elimination of methyl trimethylsilyl ether (eq 3).6

Diels-Alder Reactions.

The diene reacts with Dimethyl Acetylenedicarboxylate in toluene at reflux to give aromatic products (eq 4). Elimination of methanol predominates over loss of trimethylsilanol.2 Reaction with allenedicarboxylate gives similar products (eq 5).7

The most widely used dienophiles with (1) are quinones, such as benzoquinones,4,8 naphthoquinones,9-11 and anthraquinones,12 with or without halogen-substituents at the a-position. In general, the reaction proceeds very smoothly at rt or below to give adducts in moderate yields (50-70%). With monohalogenated quinones the reaction is rapid and the initial Diels-Alder adducts usually lose HCl to give quinone derivatives directly (eq 6).9 In the particular case of 2,6-dichlorobenzoquinone, the initial double Diels-Alder adduct was isolated as a crystalline product. X-ray crystallographic analysis of this intermediate established that the stereochemical course of the cycloaddition is via the cis-endo mode (eq 7).4 In reactions with vic-dihalogenated quinones, however, only substitution of halide by an acetoacetate residue occurs and no cycloadducts are obtained.13

These methodologies have been applied to the syntheses of quinoid substances with fused aromatic systems, such as (±)-averufin (eq 7),8 (±)-2-hydroxyaklavinone (eq 8),10 and naphthopyran antibiotics.13 Reaction with a sulfonamide dienophile gives adducts which are converted to potential anti-inflammatory drugs, oxicams (eq 9).14

Reactions with Electrophiles.

The diene reacts as a masked acetoacetate dianion with various electrophiles such as halogens,3 carbonyls,3,15-17 acetals,18-20 acyl halides,3 and imines.21 These reactions give 4-substituted acetoacetates and their derivatives exclusively, and are promoted by Lewis acids such as Titanium(IV) Chloride, Trimethylsilyl Trifluoromethanesulfonate, Tin(II) Chloride, etc. (eq 10).

These reactions have been applied to the synthesis of sclerin,3 (±)-D1-tetrahydrocannabinol (eq 11),18 (-)-pestalotin (eq 12),15 sperabilins,17 (+)-dihydrocompactin,16 and (+)-mevinolin analogs.20 In the case of pestalotin synthesis, highly diastereoselective condensation is executed by the addition of the diene to a solution of TiCl4 and 2-benzyloxyhexanal (syn:anti = 99:1). Addition of TiCl4 to a mixture of the diene and the aldehyde, however, gives a mixture of diastereomers (syn:anti = 54:46).

A synthesis of substituted dihydrofurans involves treatment of (1) with Tetra-n-butylammonium Fluoride to give the ester enolate, which reacts with a cyclohexadiene-Co complex (eq 13).22

Other Annulation Reactions.

Reactions with 1,2-,23 1,3- (eq 14),24 1,4-, and 1,5-dicarbonyl compounds or their derivatives (eq 15)25 give annulation products with five- to eight-membered rings via double aldol-type cyclocondensations.

1. Petrzilka, M.; Grayson, J. I. S 1981, 753.
2. Yamamoto, K.; Suzuki, S.; Tsuji, J. CL 1978, 649.
3. (a) Chan, T.-H.; Brownbridge, P. CC 1979, 578. (b) Chan, T.-H.; Brownbridge, P. JACS 1980, 102, 3534. (c) Chan, T.-H.; Brownbridge, P.; Brook, M. A.; Kang, G. J. CJC 1983, 61, 688.
4. Bell, S. H.; Cameron, D. W.; Feutrill, G. I.; Skelton, B. W.; White, A. H. TL 1985, 26, 6519.
5. Anderson, G.; Cameron, D. W.; Feutrill, G. I.; Read, R. W. TL 1981, 22, 4347.
6. Jullien, J.; Pechine, J. M.; Perez, F.; Piade, J. J. TL 1982, 23, 4943.
7. Roush, W. R.; Murphy, M. JOC 1992, 57, 6622.
8. O'Malley, G. J.; Murphy, R. A., Jr.; Cava, M. P. JOC 1985, 50, 5533.
9. Cameron, D. W.; Feutrill, G. I.; Perlmutter, P. AJC 1982, 35, 1469.
10. Tanaka, H.; Yoshioka, T.; Shimauchi, Y.; Yoshimoto, A.; Ishikura, T.; Naganawa, H.; Takeuchi, T.; Umezawa, H. TL 1984, 25, 3351.
11. Grunwell, J. R.; Karipides, A.; Wigal, C. T.; Heinzman, S. W.; Parlow, J.; Surso, J. A.; Clayton, L.; Fleitz, F. J.; Daffner, M.; Stevens, J. E. JOC 1991, 56, 91.
12. Cameron, D. W.; de Bruyn, P. J. TL 1992, 33, 5593.
13. Cameron, D. W.; Crosby, I. T.; Feutrill, G. I. TL 1992, 33, 2855.
14. Burri, K. F. HCA 1990, 73, 69.
15. (a) Hagiwara, H.; Kimura, K.; Uda, H. CC 1986, 860. (b) Hagiwara, H.; Kimura, K.; Uda, H. JCS(P1) 1992, 693.
16. Hagiwara, H.; Konno, M.; Uda, H. CC 1992, 866.
17. Hashiguchi, S.; Kawada, A.; Natsugari, H. JCS(P1) 1991, 2435.
18. Chan, T.-H.; Chaly, T. TL 1982, 23, 2935.
19. (a) Yokoyama, Y. S.; Elmoghayar, M. R. H.; Kuwajima, I. TL 1982, 23, 2673. (b) Yokoyama, Y. S.; Inoue, T.; Kuwajima, I. BCJ 1984, 57, 553.
20. Johnson, W. S.; Kelson, A. B.; Elliott, J. D. TL 1988, 29, 3757.
21. Attrill, R. P.; Barrett, A. G. M.; Quayle, P.; Van der Westhuizen, J.; Betts, M. J. JOC 1984, 49, 1679.
22. Barinelli, L. S.; Nicholas, K. M. JOC 1988, 53, 2114.
23. Chan, T.-H.; Brook, M. A. TL 1985, 26, 2943.
24. Kang, G. J.; Chan, T.-H. JOC 1985, 50, 452.
25. (a) Molander, G. A.; Andrews, S. W. TL 1989, 30, 2351. (b) Molander, G. A.; Cameron, K. O. JOC 1991, 56, 2617.

Takeshi Kitahara

The University of Tokyo, Japan

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