Synthesis, characterization and assignment of the Absolute Configuration of 4,4-dimethyl-5-oxo-tetrahydrofuran-3-carboxylic acid and its esters: a combined experimental and theoretical investigation

The synthesis of a new, optically active, paraconic-acid derivative 4,4-dimethyl-5-oxo-tetrahydrofuran- 3-carboxylic acid and its methyl and ethyl esters was accomplished by a procedure involving the kinetic enzymatic resolution of the racemic ethyl ester. Thus, ethyl (+)-4,4-dimethyl-5-oxo-tetrahydrofuran-3- carboxylate, derived from a ring fission, was isolated at low conversion values, with 94% ee using HLAP as the enzymatic source. The corresponding enantiomerically pure acid was also obtained. The absolute configuration of the products was determined based on the results of an extensive computational study of the specific rotation of the acid and methyl ester. Four different wavelengths were considered and comparisons with the sign and magnitude of the corresponding experimental observations were carried out. Solvent effects on both the conformational space and the specific rotation were included in the computations using the Polarizable Continuum Model. The assigned absolute configuration of the title compounds is (R)-(+), which is in agreement with a tentative experimental assignment based on an analysis of the circular dichroism curves.