Malonic esters, reaction with

An other procedure for constructing this ring system started with 2-methylbenzimidazole 583 whose reaction with malonic ester 584 gave 585... 

The cz5-aziridine substrate shows, as expected on the basis of this model, predominant formation of the trans-cyclopropane product. The starting materials for this MIRC reaction can readily be obtained from the aziridine esters by reduction to the corresponding aldehyde and a subsequent Knoevenagel reaction with malonate ester (Scheme 25) [34]. 

These model reactions were of great value in the extension of the C-glycosylation reaction with malonic esters to five-membered ring-systems. Treatment of 2,3 5,6-di-O-isopropylidene-a-D-manno-furanosyl bromide122,123 (150) with diethyl sodiomalonate led to an anomeric mixture of C-glycosyl compounds that could be separated by column chromatography, with the a (151) and /B (152) anomers in... 

Table 8. Electrogenerated superoxide reaction with malonate esters ...

The synthesis of 2,2-dimethylsuccinic acid (Expt 5.135) provides a further variant of the synthetic utility of the Knoevenagel-Michael reaction sequence. Ketones (e.g. acetone) do not readily undergo Knoevenagel reactions with malonic esters, but will condense readily in the presence of secondary amines with the more reactive ethyl cyanoacetate to give an a, /f-unsaturated cyanoester (e.g. 15). When treated with ethanolic potassium cyanide the cyanoester (15) undergoes addition of cyanide ion in the Michael manner to give a dicyanoester (16) which on hydrolysis and decarboxylation affords 2,2-dimethylsuccinic acid. 

Several approaches to the synthesis of morphinans start with cyclohexanone intermediates leading to octahydroisoquinolines such as 3 by way of a route similar to that exploited by Grewe (Scheme 3.1). Amination of 2-hydroxymethylenecyclohexanone (6) followed by reaction with malonic ester afforded the hexahydroisoquinoline, 7, that was decarboxylated and converted on a commercial scale to 5,6,7,8-tetrahydroisoquinoline(9) via the 3-chloro intermediate. 

Scheme 1.2 8 2 reaction with malonic ester enolates. 

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