Tetramethyl 1,1,4,4-cyclohexanetetracarboxylate: preparation and conversion to key precursors of fluorinated, stereochemically defined cyclohexanes

Stereoselective low-temperature diisobutylaluminum hydride (DIBALH) reduction of the title tetraester 3 affords trans-1,4-dialdehyde 4a as the major product. Fluorination of 4a,b, followed by additional elaboration leads to novel, 1,1,4,4-tetrasubstituted cyclohexanes bearing trans-1,4-difluoromethyl and fluoromethyl groups. The effect of ring size and number of ester substituents on the outcome of the reduction has been examined and treatment of dimethyl 1,1-cycloalkyl diesters 7a-c with excess DIBALH results in reduction of only one ester group. An entry into trans-1,4-trifluoromethylated tetrasubstituted cyclohexanes has been gained through stereoselective SF4 fluorination of 1,1,4,4-cyclohexanetetracarboxylic acid 17. Stereochemical assignments are supported by X-ray crystallographic data.