Weiler dianion

Synthesis of the Diels-Alder precursor began with 56, which was able to react with the Weiler dianion, giving 57 in 64% yield (Scheme 11). Following this, the ketone of 57 was stereoselectively reduced with ammonium boro-hydride due to binding of the alcohol to the boron species at the p-position. Treatment of the resulting alcohol with trifluoroacetic acid converted the ester to the carboxylic acid, which rapidly cyclized to form lactone 58 in 36% yield over two steps. Protection of the alcohol with a triethylsilyl group gave 59,... 

Weiler Modification-. By using very strong bases, a dianion can be formed that will preferentially alkylate at the methyl group ... 

Neeland, E. G. Sharadendu, A. Weiler, L. Alkylation of the dianion of 3-oxo-13-tetradeca-nolide. Tetrahedron Lett. 1996, 37, 5069-5072. 

The method of Huckin and Weiler has enjoyed widespread use in synthesis. For example, recently reported syntheses of rrans-bicyclo[4.3.1]decan-10-one and a bicyclo[4.4.1]undecan-7-one derivative have employed y-alkylations of 3-keto ester dianions as key steps. This methodology has also been extended to the formation and y-alkylation of dianions of y,8-unsaturated P-keto esters. ... 

A word about the synthesis of the a-series, a-geraniol (73) and a-nerol (74), is warranted because they are often intermediates in the synthesis of 1-hydroxylated compounds (e.g., some diols described below). Weiler has continued his exploitation of the dianion of methyl acetoacetate to this end. Instead of prenylation (Vol. 4, p. 461, Ref. 73) he carried out a similar series of operations by alkylating the dianion with 4-bromo-2-methyl-l-butene, thus arriving at compounds of the a-series via the keto ester 75, methylating the enol phosphate to 76. He also prepared the double methylene isomer 77 (R = COEt) of geranyl propionate from the intermediate 75. The purpose of synthesizing this propionate was to prepare the pheromone of the San Jose scale, Quadraspidiotus pernicious, which is a mixture of the propionates of 73, 74,... 

Dicarbonyl compounds may be converted into dianions, which react with electrophiles at the more basic site. Huckin and Weiler found that 3-keto ester dianions undergo aldol addition reactions at the more basic methyl position (equation 32). The lithium/sodium dianion shows surprisingly weak reactivity, giving the aldol in only 11% yield after 1 h at -78 °C In contrast, the lithium enolates of simple ketones and esters, which should be much less basic than the 3-keto ester dianion, react with aldehydes to give nearly quantitative yields of aldols in THF in seconds at -78 °C. ° Seebach and Meyer also studied this reaction, and obtained the oxolactone (equation 33). Simple diastereoselection in the reaction of 3-keto ester dianions has also been studied (vide infra). 

Weiler et al have employed their jS-keto-ester dianion y-alkylation technique to produce, in one step, 5-alkoxy-j8-keto-esters of known utility in Robinson-type annelation sequences. ... 

Methyl acetoacetate added dropwise with ice-cooling under Ng to 50%-NaH-mineral oil and dry tetrahydrofuran, stirred 10 min. at 0°, then n-butyllithium in hexane added dropwise to the resulting monoanion to produce the dianion, again stirred 10 min. at 0°, methyl iodide in dry tetrahydrofuran added, and stirred 15 min. at room temp. methyl 3-oxovalerate. Y 81%. F. e. s. L. Weiler, Am. Soc. 92, 6702 (1970). 

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