Dimethyl 2-oxoglutarate

Dimethyl-6-octen-l-ol, c275 Dimethylolpropionic acid, b201 Dimethyl 3-oxoglutarate, d325... 

The 3-oxo-2//-furans (260) obtained from the reaction of a-halogenoacyl halides with /3-ketonic esters at -20 °C show no tendency to enolize to the hydroxyfurans (261) but rather behave as unsaturated ketones (Scheme 71) (73RTC731). 2,4-Dialkylfurans (262) are obtained by condensation of acyl halides with allyl halides catalyzed by aluminum chloride (73KGS1434). The acid catalyzed condensation of 2-chlorocyclopentanone with dimethyl /3-oxoglutarate leads to the furan ester (263) (77JHC711). 

In the Weiss reaction (Scheme 4), an 7-dicarbonyl compound (38) condenses with two molecules of dimethyl 3-oxoglutarate (39 E = CC Me) to give a c w-bicyclo [3.3.0] oct-ane-3,7-dione tetraester (40) the one-pot reaction produces considerable complexity, with the sequential formation of four C—C bonds. Simple acid treatment removes the carbomethoxy groups, if deshed. While die reaction involves aldol and Michael sequences, die intermediacy of a cyclopentenone [4-hydroxycyclopent-2-enone (41)] has up to now been unproven. A series of such 1 1 adducts has now been reported for a variety of diketones, together with evidence diat diey are indeed intermediates en route to the bicyclo system.62 Electronic and steric effects on the reaction are also discussed in detail. 

Further evidence for the intermediacy of 4-hydroxycyclopent-2-en-l-ones (1 1 adducts) in the Weiss reaction of 1,2-dicarbonyl compounds It1 COCOR2 with dimethyl 3-oxoglutarate (MeC CCHk CO, to give cA-bicyclo [3.3.0] octane tetraesters, has been reported and steric effects on the condensation have been explored.39... 

Dimethyl methylphosphonate, 203 Dimethyl(methylthio)sulfonium tetrafluoroborate, 204-206 Dimethyl 2-oxoglutaconate, 206-207 Dimethyl 3-oxoglutarate, 193-194... 

In a very similar manner, tandem 1,6- and 1,4-additions of -dicarbonyl compounds to methyl 2,4-pentadienoate were utilized by Danishefsky and coworkers- foi the formation of several bi- and tricyclic ring systems. For example, reaction of the enolate of dimedone with this ester gave the expected 1,6-addition product protonation/deprotonation set the stage for a subsequent intramolecular 1,4-addition (equation 9). Likewise, a ketodiester was used to transform the pentadienoate in a one-pot procedure by consecutive 1,6- and 1,4-additions into a richly functionalized tricyclic product which was then converted into the natural product ( )-cpiclovane (equation 10). According to this principle, Irie and coworkers obtained several decalin-2,7-diones by treatment of 2-methylen-2-cyclohexenones with dimethyl 3-oxoglutarate. 

Bringmann has reported a similar cyclization. Reaction of lithiopotassioacetone with the ethylene ketal of dimethyl 3-oxoglutarate provides phenol (151) in 19% yield (equation 154). Again, the intermediate tetraketone eludes isolation. A series of transformations serves to convert (151) into the isoquinoline (152). 

A mixture of dimethyl 3-oxoglutarate and 5-dimethylamino-1-phenyl-1,4-pentadiene-3-one in dioxan containing acetic acid and potassium fluoride upon refluxing overnight underwent Michael addition and afforded dimethyl 2-hydroxy-4-(2-phenylethenyl)-1,3-benzenedicarboxylate in 63% yield (ref.51). 

A number of stimulating and instructive synthetic achievements have been reported. A convenient synthesis of 1-desoxylycorinone (10), a degradation product of lycorine, has been announced (Scheme 1). The oxazolone (3), readily prepared from piperonal and hippuric acid in the presence of acetic anhydride and sodium acetate, was treated with the sodium salt of dimethyl 3-oxoglutarate... 

In 2(X)9, Hayashi and co-workers [52] developed a Michael-Knoevenagel cascade reaction between enals and dimethyl-3-oxoglutarate (79) furnishing cyclohexenes (80) in good yields and enantioselectivities. In this case, the absence of base allows the single addition of one molecule of dimethyl-3-oxoglutarate to the enal. 

The reaction of dimethyl 3-oxoglutarate with glyoxal in aqueous acidic solution gives [3,3.0] octane, 3,7-dione-2,4,6,8-tetracarboxylate and on acid catalysed hydrolysis followed by decarboxylation it gives cis-bicyclo[3.3.0] octane-3,7-dione (Scheme 152). The reaction is believed to involve a double Knoevenagal reaction that gives an a,P-unsaturated y-hydroxycyclopentenone, which reacts with another molecule of dimethyl 3-oxoglutarate by Michael addition. 

Pt(CHCH2CH2)Cl(PMeaPh)2], respectively. Dimethyl 3-oxoglutarate reacts with the complexes [PtL4] (L=PPhs or PMeaPh) to afford the products (49), which in turn react with (CF8)aCO to yield the complexes (50). Diphenyl-cyclopropenone reacts with [Pt3(CN Bu)g] and [Pt(cod)(MeCOCH=CH2)2] in... 

Full details of a new route to cw-decalins via a double Michael reaction have appeared. This involves conjugate 1,6-addition of dimethyl 3-oxoglutarate (176) to the dienone (177), followed by a stereoselective intramolecular 1,4-Michael addition. 

The potassium fluoride-catalysed double Michael addition of dimethyl 3-oxoglutarate to the 4-methylenecyclohex-2-enones (156 R, = H or Me) in... 

The yields of the reaction depend on both steric demand of the substituent of the 1,3-dicarbonyl compounds and the electronic nature of this substituent. Very good yields were obtained by employing dimethyl 3-oxoglutarate 68 or methyl 4-methoxy-3-oxobutanoate 69. The lowest yields were observed while using with methyl 4,4-dimethoxy-3-oxobutanoate 70 or diethyl 2-oxaloacetate 71. 

SCHEME 2.15 Reactions of dimethyl 3-oxoglutarate with ribose 4, arabinose 2, xylose 22, glucose 33, or galactose 34. 

K-ferf-butoxide added gradually to a stirred soln. of 2-phenyl-4-benzylidene-2-oxazolin-5-one and dimethyl 3-oxoglutarate in tetrahydrofuran, and allowed... 

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