[106875-55-2]  · C9H18O3Si  · 1,3-Dimethoxy-1-trimethylsilyloxy-1,3-butadiene  · (MW 202.32) (E)

[74272-66-5] (Z)


(diene in Diels-Alder reactions; nucleophile)

Physical Data: bp 54 °C/0.5 mmHg.

Analysis of Reagent Purity: IR (film) 1660, 1270, 1255, 845 cm-1; 1H NMR (199.5 MHz, CDCl3) d 4.32 (d, J = 1 Hz, 1 H), 4.00 (dd, 2 H), 3.53 (d, 6 H), 0.28 (s, 9 H); 13C NMR (50.10 MHz, CDCl3) d 157.9, 89.6, 77.8, 74.9, 54.1, 53.1, -0.6. The stereochemistry of the diene has been determined to be (Z) by NOE experiments.1

Preparative Method: enol silylation of methyl (E)-3-methoxy-2-butenoate, which is prepared from methyl acetoacetate and trimethyl orthoformate.2

Purification: the diene should be distilled at the lowest possible temperature to avoid intramolecular silyl migration which occurs above 80 °C.

Handling, Storage, and Precautions: stable in an inert atmosphere under anhydrous conditions when stored at 5 °C for several months. Use in a fume hood.

Diels-Alder Reactions.

Diels-Alder reactions of quinones with a variety of polarized dienes is an efficient method for the synthesis of highly substituted anthraquinones. The regioselectivity of the reaction is controlled by hydroxy,3 halo (eq 1),4 and sulfonyl5 directing groups on the dienophile. In most cases, methanol is lost in preference to TMSOH during aromatization.6

In the presence of Lewis acids the diene condenses with aldehydes and unactivated ketones in a regiospecific manner to provide d-lactones in good yield.7 The diene has also been used to trap photochemically generated thioformaldeyde.8 While Eu(hfc)37 and oxovanadium(IV) complex9 catalysts have been reported to induce asymmetry in cycloadditions with Danishefsky's diene, zero or very poor optical yields have been obtained with this diene under the same conditions. This suggests that substituents at the 1-position of the diene make a critical contribution to the asymmetric induction.7,9

Diastereoselective hetero Diels-Alder reactions have been successful in Eu(hfc)3 catalyzed condensations of the diene with a-alkoxy7,10 and a-amino aldehydes (eq 2).11 Cycloaddition with a-alkoxy imines requires a strong Lewis acid such as Diethylaluminum Chloride to ensure rapid reaction and to suppress polymerization of the diene.12 The degree of diastereoselectivity is dependent on the alkyl side chain and the alkoxy or amine protecting group. Amino acid esters have been used as chiral auxiliary groups in reactions of the diene and imines with EtAlCl2 as catalyst (eq 3).13


Nucleophilic attack by the diene on 2,3,5-tri-O-benzyl-D-ribofuranosyl acetate in the presence of Trimethylsilyl Trifluoromethanesulfonate occurs at the carbonyl carbon of the 2-benzyloxy group instead of at the C-1 carbon of the in situ generated oxonium ion (eq 4).14

Related Reagents.

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

1. Bell, S. H.; Cameron, D. W.; Feutrill, G. I.; Skelton, B. W.; White, A. H. TL 1985, 26, 6519.
2. (a) Savard, J.; Brassard, P. TL 1979, 51, 4911. (b) Savard, J.; Brassard, P. T 1984, 40, 3455. (c) Midland, M. M.; Koops, R. W. JOC 1990, 55, 5058.
3. Cameron, D. W.; De Bruyn, P. J. TL 1992, 33, 5593.
4. Brisson, C.; Brassard, P. JOC 1981, 46, 1810.
5. (a) Iwao, M.; Kuraishi, T. BCJ 1987, 60, 4051. (b) Watanabe, M.; Tsukazaki, M.; Hamada, Y.; Iwao, M.; Furukawa, S. CPB 1989, 37, 2948.
6. Examples where the methyl ether is the major product: (a) Coleman, R. S.; Grant, E. B. JOC 1991, 56, 1357. (b) Paquet, J.; Brassard, P. CJC 1989, 67, 1354.
7. Midland, M. M.; Graham, R. S. JACS 1984, 106, 4294.
8. Ward, D. E.; Gai, Y.; Zoghaib, W. M. CJC 1991, 69, 1487.
9. Togni, A. OM 1990, 9, 3106.
10. Midland, M. M.; Koops, R. W. JOC 1990, 55, 5058.
11. (a) Midland, M. M.; Afonso, M. M. JACS 1989, 111, 4368. (b) Midland, M. M.; Koops, R. W. JOC 1990, 55, 4647.
12. Midland, M. M.; Koops, R. W. JOC 1992, 57, 1158.
13. Waldmann, H.; Braun, M.; Dräger, M. TA 1991, 2, 1231.
14. (a) Yokoyama, Y. S.; Inoue, T.; Kuwajima, I. BCJ 1984, 57, 553. (b) Yokoyama, Y. S.; Elmoghayar, M. R. H.; Kuwajima, I. TL 1982, 23, 2673.

Megan Murphy

Zeneca Pharmaceuticals, Wilmington, DE, USA

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