The preferred conformation of erythro- and threo-1,2-difluorocyclododecanes

Abstract

Cyclododecane adopts a square-like structure with corner and edge CH2 groups. In this study erythro- and threo-1,2-difluorocyclododecanes were prepared to explore whether the two vicinal C–F bonds, with different relative configurations, preferably locate at corner/edge or edge/edge locations. Conformational analysis comparing the diastereoisomers was explored by using a combination of 19F{1H} NMR spectroscopy, computational studies and, in the case of the threo isomer, X-ray structural analysis. In the lowest energy conformers for both diastereoisomers the vicinal C–F bonds are located corner/edge, rather than edge/edge. These structures avoid placing a C–F bond endo into the ring, and appear to benefit from C–CHF–C angle widening, which relaxes 1,4-H,H transannular interactions.

Keywords

• alicyclic chemistry
• conformational analysis
• cyclododecane
• 19F NMR
• organo-fluorine chemistry
• transannular interactions