Ethyl acetoacetate, bromo-derivative

Although bromo derivatives have been used, the two most common ot-halocarbonyl compounds for this reaction are chloroacetaldehyde and chloroacetone. The dicarbonyl component is typically ethyl acetoacetate or one of its derivatives. A variety of bases including triethylamine and potassium hydroxide can promote the reaction however, the most popular base is pyridine. Conversion to the furan takes place either at room temperature or upon heating to 50°C with reaction times varying from four hours to five days and yields ranging from 30-86%. 

More recent reports from Cordova [155] and Wang [156] have described the cyclopropanation of a, P-unsaturated aldehydes 99 with diethyl bromomalonates 100 and 2-bromo ethyl acetoacetate catalysed by a series of diaryIprolinol derivatives. Both describe 30 as being the most efficient catalyst in many cases and optimal reaction conditions are similar. Some representative examples of this cyclopropanation are shown in Scheme 40. The transformation results in the formation of two new C-C bonds, a new quaternary carbon centre and a densely functionalised product ripe for further synthetic manipulation. Triethylamine or 2,6-lutidine are required as a stoichiometric additive in order to remove the HBr produced during the reaction sequence. The use of sodium acetate (4.0 equivalents) as an additive led to subsequent stereoselective ring opening of the cyclopropane to give a,P-unsaturated aldehydes 101. It can be envisioned that these highly functionalised materials may prove useful substrates in a variety of imin-ium ion or metal catalysed transformations. 

Treatment of perhydro-4-azaazulene (3) with mercuric acetate produces a mixture of dehydro derivatives 31a and 31b, which, with acids, yields homogeneous salts of structure 32 (56JOC344). The enamine 34, which was obtained by the same route from 33, served as a model compound in a study of the synthesis of cephalotaxine (72JOC3691). A reaction with ethyl y-bromo-acetoacetate surprisingly yielded the quinolizidine 36, which was formed by rearrangement of the intermediate annellation product 35 (Scheme 3) Phthalimides 38 were obtained from a Baeyer-Villiger oxidation of 4-azaazulen-3-ones 37 (77JOC1093). 

I -epimer was encountered. Condensation of various 1-alkylamino-l-deoxy-D-arabino-hexuloses with ethyl acetoacetate afforded a series of pyrrole derivatives with a D-arabino-hexityl side chain at C-3 [e.g. (52)] and condensation of l-bromo-l-deoxy-D-nZ)o-hexulose with HSC(=NH)C02Et afforded the thiazole (53). Cyclization of D-penicillamine with 2,3,4,5-tetra-O-acetyl-flWe/ijdo-L-arabinose afforded, after f -deacetylation the thiazolidine (54) as a mixture of two diastereoisomers. The tetrazoles (55) are prepared by condensation of the appropriate benzoylated aldononitrile with ammonium azide, followed by 0-debenzoylation... 

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See also in sourсe #XX -- [ ]

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