Tetramethoxyethylene1

[1069-12-1]  · C6H12O4  · Tetramethoxyethylene  · (MW 148.18)

(strong electron-rich ketene acetal which reacts as an oxalyl dication equivalent with a variety of electrophiles).

Physical Data: bp 48 °C/15 mmHg.

Preparative Methods: the best preparative method is from (p-chlorophenoxy)dimethoxymethane and Sodium Hydride (eq 1).2 This method is also applicable for other tetraalkoxy analogs.

Handling, Storage, and Precautions: the compound should be stored in dry, base-rinsed vessels under nitrogen.

Introduction.

Tetramethoxyethylene, as a very electron-rich alkene, belongs to the class of ketene acetals. Due to its symmetrical electron distribution, its reactivity is generally somewhat lower than the more polarized ketene acetals, e.g. the 1,1-dialkoxyalkenes. The general reactivity towards electrophiles was first explored by Hoffmann et al.1a A variety of cationic species such as diazonium salts add to tetramethoxyethylene to yield substituted methyl dimethoxyacetates (eq 2).

Dihalocarbenes add to give 1,1-dihalotetramethoxycyclopropanes, which upon reaction with n-Butyllithium are converted into the electron-rich tetramethoxyallene (eq 3).

The most important applications are in the field of cycloadditions.1c Generally these reactions occur with fewer side products than those of the 1,1-dialkoxyalkenes and the cycloadducts obtained are more stable.

[2 + 2] Cycloadditions.

With a variety of electron-poor alkenes, tetramethoxyethylene reacts to give tetramethoxycyclobutanes.3 These higly oxygenated cyclobutanes are valuable precursors for the synthesis of a,a-dimethoxy esters,4 1-cyano-2-aryl-3,3,4,4-tetramethoxycyclobutenes,5 1-cyano-2-arylcyclobutenediones,6 and 1,1,4,4-tetramethoxybuta-1,3-dienes (eq 4).7

With aldehydes in the presence of Lewis acids, 2,2,3,3-tetramethoxyoxetanes are formed in good yields (eq 5).8 These can be easily hydrolyzed to a,a-dimethoxy-b-hydroxy esters.

Under the influence of Lewis acids, a,b-unsaturated carbonyl compounds yield either cyclobutanes or oxetanes depending on the structure of the a,b-unsaturated carbonyl compound (eq 6).1c,9 These reactions can also be performed at high pressure without Lewis acids.

The thermal reaction with ketene yields mixtures of 2,2,3,3-tetramethoxycyclobutanone and 2,2,3,3-tetramethoxy-4-methyleneoxetane.10 In the presence of Lewis acids the oxetane is selectively formed.1c The cycloadducts from tetraalkoxyethylenes and ketenes have been applied effectively in the synthesis of 1,2-substituted tetramethoxycyclobutenes, 1-substituted 4-oxotrimethoxycyclobutenes, and squaric acid.11

Other Cycloadditions.1c

Diels-Alder adducts are only obtained from electron-poor dienes or a,b-unsaturated carbonyl compounds having a preferred cisoid conformation. Epoxides behave like 1,3-dipoles when adding to tetramethoxyethylene in the presence of Lewis acids to give 2,2,3,3-tetramethoxy(tetrahydrofurans). Diaryl a-diketones yield [4 + 2] cycloadducts with tetramethoxyethylene (eq 7), whereas electronically asymmetric ketene acetals give oxetanes and bis-oxetanes.

An inverse demand Diels-Alder reaction is also reported with dimethyl 1,2,4,5-tetrazine-3,6-dicarboxylate (eq 8).1a

Related Reagents.

1,2-Diethoxy-1,2-bis(trimethylsilyloxy)ethylene; Ketene Bis(trimethylsilyl) Acetal; Ketene Diethyl Acetal; 1-Methoxy-1-(trimethylsilyloxy)propene; 1-Methoxy-2-trimethylsilyl-1-(trimethylsilyloxy)ethylene; Methylketene Bis(trimethylsilyl) Acetal; Methylketene Dimethyl Acetal; Tris(trimethylsilyloxy)ethylene.


1. (a) Hoffmann, R. W. AG 1968, 80, 823; (AG(E) 1968, 7, 754). (b) Seebach, D. MOC 1971, B4/4, 340. (c) Scheeren, J. W. RTC 1986, 105, 71. (d) Scheeren, J. W. MOC 1993, BE15, 1674; (e) FF 1969, 2, 401; 1975, 5, 649.
2. (a) Scheeren, J. W.; Staps, R. J. F. M.; Nivard, R. J. F. RTC 1973, 92, 11. (b) Bellus, D.; Fischer, H.; Greuter, H.; Martin, P. HCA 1978, 61, 1784.
3. Scheeren, H. W.; Frissen, A. E. S 1983, 794.
4. Ooms, P. H. J.; Scheeren, J. W.; Nivard, R. J. F. S 1975, 662.
5. Ooms, P. H. J.; Scheeren, J. W.; Nivard, R. J. F. S 1975, 260.
6. Ooms, P. H. J.; Scheeren, J. W.; Nivard, R. J. F. S 1975, 639.
7. Ooms, P. H. J.; Scheeren, J. W.; Nivard, R. J. F. S 1975, 263.
8. Scheeren, J. W.; Aben, R. W. M.; Ooms, P. H. J.; Nivard, R. J. F. JOC 1977, 42, 3128.
9. Aben, R. W. M.; Scheeren, J. W. TL 1985, 26, 1889.
10. Hoffmann, R. W.; Bressel, U.; Gehlhaus, J.; Häuser, H. CB 1971, 104, 873.
11. Bellus, D. JOC 1979, 44, 1208.

J. (Hans) W. Scheeren

University of Nijmegen, The Netherlands



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