On the synthesis of 3,4-dihydroxyprolines. I. cis-Glycolation of 3,4-dehydroproline derivatives

The interaction of OsO4 and protected derivatives of 3,4-dehydro-DL-proline gives high yields of 2,3-trans-3,4-cis-3,4-dihydroxy-DL-proline derivatives, with only traces of the 2,3-cis-3,4-cis diastereoisomers. Corresponding α-glycolation with KMnO4 gives mixtures of the 2,3-trans-3,4-cis and 2,3-cis-3,4-cis isomers in the ratio 1 : 1. Separation of the components of such mixtures is extremely difficult. The free amino acids in these two families of the 3,4-dihydroxy-DL-prolines have been characterized. Epimerization at C2 of 2,3-cis derivatives occurs readily. O-Tosylation of the 2,3-cis series occurs more readily than for other hydroxyprolines. Esters of N,O,O-tritosyl-2,3-trans-3,4-cis-3,4-dihydroxyproline are converted very rapidly by mild alkali into the equivalent esters of X-tosylpyrrole-2-carboxylic acid. For the corresponding N,O,O-tritosyl carboxylic acid, decarboxylation also takes place during aromatization, to yield N-tosylpyrrole.