Mesoxalates, cycloaddition

Mesoxalates are highly reactive substrates because of their strongly polarized carbon-oxygen bond. They have been used in pericyclic processes (e.g. Diels-Alder reactions,8 ene reactions,9 [3+2]10 and [2+2]11 cycloadditions), in aldol12 and Wittig as well as Friedel-Crafts reactions.13 Further applications arise from the use of the corresponding imines in hetero Diels-Alder reactions14 and electrophilic cyclizations.15... 

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. 

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. 

For preparative purposes, the reaction of thiocarbonyl ylides with carbonyl compounds can be considered as an alternative method for the synthesis of 1,3-oxathiolanes. Aromatic aldehydes, chloral, glyoxalates, mesoxalates, pyruvates as well as their 3,3,3-trifluoro analogues are good intercepting reagents for thioketone (5)-methylides (36,111,130,163). All of these [3 + 2] cycloadditions occur in a regioselective manner to produce products of type 123 and 124. 

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 [4 + 2] cycloaddition of dienes 1 with ethyl mesoxalate (11) gives a mixture of two adducts 12 and 13 which differ in the configuration at C-l. Depending on the chiral auxiliary used, adducts with predominantly S or R configuration at C-l can be obtained. 

The chiral europium complex F.u(hfc)3 has also been used as catalyst for the cycloaddition of diethyl mesoxalate (21a) and butyl glyoxylate (21b) to 1-methoxy-l,3-butadiene (20a) and... 

Butyl glyoxylate reacts normally only with l ,3-butadienyl ether 289. However, David and co-workers have found that with the more active dienophile, diethyl mesoxalate, lZ,3-butadienyl ether (290) could also enter into cycloaddition, although the reaction was appreciably slower. The resulting cycloadducts 293 and 294 were decarboethoxylated according to the Krapcho method, furnishing the a-o (295) and a-L (296) as the main products. 

Significant improvement in the synthesis of disaccharides by cycloaddition may be achieved by reaction of diethyl mesoxalate with the dienyl ethers of protected sugars. This more active dienophile adds to both cis- and trans-ethers, unlike compounds hitherto reported, and more efficient utilization of the protected starting sugar is possible. 

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