[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.
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.
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
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
J. (Hans) W. Scheeren
University of Nijmegen, The Netherlands