The Conformational Behaviour of Fluorinated Tetrahydrothiopyran

Abstract

We present a comprehensive study on the conformational behavior of diversely substituted 4‐fluorotetrahydrothiopyran derivatives. Through quantum chemical simulations including DFT as well as NBO and NPA analysis, we elucidate the pivotal role of electrostatic interactions, occasionally complemented by hyperconjugative interactions, in stabilizing axial fluorine conformers. Less polar conformers were occasionally obtained, attributed to the interplay of electrostatic and hyperconjugative interactions. Experimental validation through NMR spectroscopy aligns with the computational analysis, thus providing a coherent understanding of the structural dynamics of these compounds.