Carbonyl groups as heterodienophiles in aqueous media

The initial studies of Lubineau et al. [41] focused on reacting cyclopentadiene with aqueous glyoxylic acid at different pH levels. The reaction rate increased substantially at lower pH. At pH 0.9, the reaction of cyclopentadiene in aqueous glyoxylic acid provides a-hydroxy-y-lactones 128 and 129 in 83% yield (73/27 ratio) after stirring the heterogeneous mixture for 1.5 h at 40°C  

Product formation was postulated to arise from the spontaneous rearrangement of the initially formed hetero Diels-Alder adducts 127. The similar reaction when performed with an alkyl glyoxylate in the absence of water (neat) or in organic solvent (toluene) inevitably leads to cyclopentadiene dimerization instead of the expected cycloaddition. 

The reaction of cyclohexadiene with aqueous glyoxyhc acid at pH 1 is complete after 2 days at 90°C, providing a-hydroxy-y-lactones 131 and 132 (60/40 ratio) in 85% yield [41]  

The hetero Diels-Alder reaction also proceeds with acyclic dienes [45]. For example, reaction of 2-methylpentadiene with aqueous glyoxylic acid furnishes, after 1.5 h at 100°C, a near-quantitative yield of dihydropyrans 133 and 134 in a 64/36 ratio  

The product ratio reflects thermodynamic conditions, as evidenced by each of the purified methyl esters (135 and 136), providing compound 133 as the major isomer when separately submitted to these reaction conditions. Substituting isoprene for 2-methylpentadiene in this reaction requires more drastic conditions (100°C, 18h) and results in a substantially lower yield (28%) of the corresponding dihydropyrans. 

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