Conformational Analysis of Acyclic α‐Fluoro Sulfur Motifs

Bioactive small molecules containing α‐fluoro sulfur motifs [RS(O)(n)CH(2)F] are appearing with increasing frequency in the pharmaceutical and agrochemical sectors. Prominent examples include the anti‐asthma drug Flovent(®) and the phenylpyrazole insecticide pyrafluprole. Given the popularity of these structural units in bioactive small molecule design, together with the varying oxidation states of sulfur, a conformational analysis of α‐fluoro sulfides, sulfoxides, and sulfones, would be instructive in order to delineate the non‐covalent interactions that manifest themselves in structure. A combined crystallographic and computational analysis demonstrates the importance of hyperconjugative donor‐acceptor interactions in achieving acyclic conformational control. The conformational disparity in the syn‐ and anti‐diastereoisomers of α‐fluorosulfoxides is particularly noteworthy.