Diethyl mesoxalate

The reaction of 1,3-cyclohexadiene and ethylglyoxylate catalyzed by the corresponding copper (II) triflate complex led to the expected product in high yield (81%) and high enantio- and diastereoselectivity. At - 40 °C, the reaction between cyclohexadiene and diethyl mesoxalate afforded similarly the expected product in high yield and up to 98% ee. 

This retention of reagents by the graphite support has been shown in a series of experiments involving volatile dienes such as 2,3-dimethylbutadiene (12) and iso-prene (13) (Tab. 7.2) [30, 31]. The reaction of 12 with diethyl mesoxalate gave 14 in 75% yield after SMW irradiation at low power (30 W) for 20 x 1 min only (Tab. 7.2, entry 1). When conventional heating was used a satisfactory yield was obtained after 4 h at 135 °C in a sealed tube [32]. Ethyl glyoxylate is a weaker carbonyl dienophile... 

Dienes do not react with carbonyl compounds unless the latter are activated by electron-withdrawing substituents such as carboxyl groups. Cyclohexa-1,3-diene, for example, adds diethyl mesoxalate (1) at 120 °C to form 2 (equation 2)2. Other cycloadditions of this ester with various dienes, which were carried out in a sealed tube at 130-135 °C, are shown in equations 3 and 43. It is noteworthy that no product was isolated from the action of diethyl mesoxalate on cyclopentadiene it was suggested3 that the cycloadduct reverted to its components at the high temperature required for the reaction. 

The presence of electron-donating substituents in the diene enables it to react with simple aldehydes thus both acetaldehyde and benzaldehyde add to 1-methoxy-1,3-butadiene at 50-65 °C under high pressure (20 Kbar) to give dihydropyrans as 70 30 mixtures of cis- and frans-isomers (equation 5)4. The combination of electron-rich diene/electron-poor dienophile makes it possible to perform the reaction under milder conditions. 2-Alkyl-l-ethoxy-1,3-butadienes and diethyl mesoxalate afford dihydropyrans almost quantitatively (equation 6)5. 

An outstandingly reactive diene is l-methoxy-3-(trimethylsilyloxy)-l,3-butadiene ( Danishefsky s diene ) 4, prepared by the action of trimethylsilyl chloride on the ketone 3 in the presence of zinc chloride/triethylamine (equation 7)6. The reaction of diethyl mesoxalate with Danishefsky s diene gives the dihydropyran 5 with the (trimethylsily-loxy)dienes 6 and 7, mixtures of dihydropyrans are obtained, in which the meta-isomers predominate (equations 8 and 9)7. 

Equation 10 shows an example of the synthesis of a chiral functionalized hexapyra-noside from diethyl mesoxalate and the butadienyl ether of a protected sugar8a,b. 

Other carbohydrate syntheses include the formation of dihydropyrans from diethyl mesoxalate and 1-methoxybutadienes (e.g. equation ll)9. The butadiene 8, which is activated by the presence of two alkoxycarbonylamino groups, adds to diethyl mesoxalate in DMF during 44 h at 180 °C in an autoclave to give the cycloadduct 9 in 34% yield (equation 12)10. 

In recent years, much work has been done on catalyzed and asymmetric cycloaddition reactions. In the presence of 5 mol% bismuth trichloride, the simple dienes 10 (R1 = R" = H R1 = H, R2 = Me or R1 = Me, R2 = H) react with diethyl mesoxalate to afford mixtures of the cycloadducts 11 and the products 12 of an ene-reaction (equation 13)11 12. 1,3-Cyclohexadiene and ethyl glyoxylate give solely the endo adduct 13 in 50% yield (equation 14)12. 

Compound 287, which is obtained from 7V-carbethoxymethyl-2-methyl-pyridinium bromide and diethyl mesoxalate, undergoes base-catalyzed cyclization to betaine 288 which is readily converted to the quinolizinium-3-olate 286 (R = COjEt, = COjH). Decarboxylation of this compound (286 R = COjEt, R = CO2H) by cupric oxide and quinoline at 180-190 C gives the unsubstituted betaine (286 R = R = Quinolizinium-3-... 

Branched-erythrono-1,4-lactones are accessible from the oxetane 66 which was derived thermally from diethyl mesoxalate 64 and 2,2-di-isopropyl-1,3-dioxole 65 [58]. An impressive improvement in the regioselectivity of oxetane formation was discovered with 2,3-dihydrofuran 67 as... 

Two heterocyclic rings can also be linked by electrophilic substitution reactions. Thus, the cyclopentadiindole (55) is formed by the treatment of a 2,2 -diindolyl with diethyl mesoxalate <92AP(325)353>, and 3,5-dithienylthiophene-2,2 -dicarboxylic acids or derivatives can be cyclized to various thienylcyclopenta[6 c j or [b b dithiophenes <84PS(20)121>. 

A convenient synthesis of aryl glycines from Grignard reagents, prepared via iodine-magnesium exchange, was performed by the reaction with N-Boc-iminomalonate (from diethyl mesoxalate and BocN=PPh3). The reaction... 

Mesoxalic acid esters tend to undergo cycloaddition reactions at their central carbonyl function. Treatment of complex 37 with an excess of diethyl mesoxalate furnished the oxadiphosphatricyclo[3.1.0.0 ]hexane 40 as a colorless oil in 17% yield after chromatography (Scheme 15). When a threefold excess of tetracyanoethene was added to a solution of 37 in dichloromethane at —85 °C the color of the reaction mixture changed spontaneously from red to black, and 1,6-diphos-phatricyclo[3.1.0.0 ]hexane 41 was isolated in 15% yield (Scheme 15) <1999S639>. 

The first report of a chiral aluminum Lewis acid employed in a heteroatom Diels-Alder reaction utilized Koga s mentholoxy dichloroaluminum catalyst 4 [75]. trans-Piperylene and 1-methoxybutadiene were reacted with n-butyl glyoxalate and diethyl mesoxalate the results are summarized in Sch. 46. The asymmetric induction and chemical yield in these reactions are quite poor but the authors did find that moderate asymmetric induction could be obtained from reactions catalyzed by Eu(hfc)3. 

Examples of the oxidation of aliphatic hydrazones are the conversion of acetone hydrazone into 2-diazopropane [386, 392], of hexafluoroacetone hydrazone into 2-diazohexafluoropropane [445], of 4-octanone hydrazone into 4-diazooctane [386], and of the hydrazone of diethyl mesoxalate into diethyl diazomalonate [935] (equations 457 and 458). 

Methylene groups in the a positions with respect to carboxylic groups are changed to carbonyl groups thus oi-keto esters are formed. Methyl phenylacetate is oxidized with air in the presence of cobalt benzoate at 110-115 °C to methyl phenylglyoxylate in 86% yield [8], Diethyl malonate is converted by nitrogen sesquioxide (N2O3) into diethyl mesoxalate in 74-76% yield [450],... 

Diethyl diazomalonate is conveniently prepared from diethyl mesoxalate (1, commercially available) in 67% overall yield by condensation with hydrazine and oxidation of the hydrazone with silver oxide in THF.12a... 

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