[61539-61-5]  · C9H18O3Si  · 1,1-Dimethoxy-3-trimethylsilyloxy-1,3-butadiene  · (MW 202.32)

(diene in Diels-Alder reactions)

Physical Data: bp 84-87 °C/10 mmHg; n23D 1.4640.

Analysis of Reagent Purity: 1H NMR (60 MHz, neat) d 4.39 (s, 1 H), 4.07 (d, J = 1.0 Hz, 1 H), 3.99 (d, J = 1.0 Hz, 1 H), 3.61 (s, 3 H), 3.52 (s, 3 H), 0.14 (s, 9 H); IR (film) 1657, 1272, 1251, 850 cm-1.

Preparative Method: enol silylation of 4,4-dimethoxy-3-buten-2-one, which is prepared from 4,4-dichloro-3-buten-2-one.1

Purification: distillation.

Handling, Storage, and Precautions: moisture sensitive; should be handled in a well-ventilated fume hood.

Diels-Alder Reactions.

This diene is more powerful than Danishefsky's diene in Diels-Alder reactions with electron-deficient dienophiles.2 The enhanced nucleophilic character of the diene apparently overrides the steric difficulties associated with the (Z)-methoxy group.

There are many examples of Diels-Alder reactions of the diene with quinones as the dienophile.1a,3 While halogen substituents on the quinone have been used to direct the regiochemistry of the addition, haloquinones are not always easy to prepare. Sulfinylquinones are a convenient alternative (eq 1).3d

The Diels-Alder reaction with methyl trans-b-nitroacrylate, an alkyne equivalent, allows access to substitution patterns that are otherwise difficult to synthesize (eq 2).4 Comparison of eq 2 with the corresponding reaction using methyl propiolate (eq 3) indicates that this represents an umpolung of Diels-Alder reactivity.2 When the alkyne is substituted as shown in eq 4, more drastic conditions are necessary (xylene, 140 °C, 18 h).5 Allenes have also been used in Diels-Alder reactions with the diene.1b,2,6

The key step in one approach to the natural product griseofulvin and its analogs involves a Diels-Alder reaction with the diene.7 For example, a tetrasubstituted dienophile was used to form three contiguous quaternary centers in the cycloaddition step shown in eq 5.7d

Seven-membered carbocycles such as heptafulvenes8 and tropones9 (eq 6) have been successfully prepared by Diels-Alder reactions of the diene with triafulvenes or cyclopropenes, respectively.

Hetero Diels-Alder Reactions.

Carbonyl compounds and the diene react in the presence of the mild Lewis acid Eu(fod)3 (eq 7)10 or Zinc Chloride11 as catalysts to give dihydropyrones in high yields. Under similar conditions, transoid dienes such as 1,1,4-trimethoxybutadiene or 1,1-dimethoxybutadiene undergo polymerization. The higher reactivity of the diene has been ascribed to its preference for the cisoid conformation.11

Related Reagents.

1,3-Dimethoxy-1-trimethylsilyloxy-1,3-butadiene; 1-Methoxy-1,3-bis(trimethylsilyloxy)-1,3-butadiene.

1. (a) Banville, J.; Brassard, P. JCS(P1) 1976, 1852. (b) Fink, M.; Gaier, H.; Gerlach, H. HCA 1982, 65, 2563.
2. Danishefsky, S.; Singh, R. K.; Gammill, R. B. JOC 1978, 43, 379.
3. (a) Botha, M. E.; Giles, R. G. F.; Yorke, S. C. JCS(P1) 1991, 85. (b) Giles, R. G. F.; Green, I. R.; Niven, M. L.; Yorke, S. C. JCS(P1) 1988, 2459. (c) Potts, K. T.; Bhattacharjee, D.; Walsh, E. B. JOC 1986, 51, 2011. (d) Kraus, G. A.; Woo, S. H. JOC 1986, 51, 114. (e) Brisson, C.; Brassard, P. JOC 1981, 46, 1810. (f) Giles, R. G. F.; Yorke, S. C.; Green, I. R.; Hugo, V. I. CC 1984, 8, 554. (g) Grandmaison, J. L.; Brassard, P. T 1977, 33, 2047.
4. Danishefsky, S.; Prisbylla, M. P.; Hiner, S. JACS 1978, 100, 2918.
5. Danishefsky, S.; Etheredge, S. J. JOC 1979, 44, 4716.
6. Yoshida, M.; Harada, N.; Nakamura, H.; Kanematsu, K. TL 1988, 29, 6129.
7. (a) Ko, B. S.; Oritani, T.; Yamashita, K. Han'guk Nonghwa Hakhoechi 1992, 35, 395 (CA 1993, 118, 212 734x). (b) Ko, B. S.; Oritani, T.; Yamashita, K. ABC 1990, 54, 2199. (c) Tomozane, H.; Takeuchi, Y.; Choshi, T.; Kishida, S.; Yamato, M. CPB 1990, 38, 925. (d) Danishefsky, S.; Walker, F. J. JACS 1979, 101, 7018. (e) Danishefsky, S.; Etheredge, S. J. JOC 1978, 43, 4604.
8. Eicher, T.; Abel, M. S 1987, 6, 542.
9. Banwell, M. G.; Knight, J. H. CC 1987, 14, 1082.
10. (a) Castellino, S.; Sims, J. J. TL 1984, 25, 2307. (b) Danishefsky, S.; Harvey, D. F.; Quallich, G.; Uang, B. J. JOC 1984, 49, 392. (c) Danishefsky, S.; Langer, M. E. JOC 1985, 50, 3672 (footnote 15 therein).
11. Van Balen, H. C. J. G.; Broekhuis, A. A.; Scheeren, J. W.; Nivard, R. J. F. RTC 1979, 98, 36.

Megan Murphy

Zeneca Pharmaceuticals, Wilmington, DE, USA

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