Effects of substitution of OH group by F atom for conformational preferences of fluorine-substituted analogues of (R,R)-tartaric acid, its dimethyl diester, diamide, and N,N,N ',N '-tetramethyl diamide. Ab initio conformational analysis

High-level ab initio methods up to MP2/6-311 ++ G**//RWF/6-31G* have been u sed to characterize the conformations of isolated molecules of (2S.3S)-2,3- dideoxy-2,3-difluorotartaric acid (FTA) and its dimethyl diester (FME), dia mide (FAR?), and N,N,N',N'-tetramethyldiamide (FTMA). A wide range of possi ble structures (84 for FTA and 63 for FME, FAM, FTMA) has been surveyed at the RHF/3-21G level. At the highest level of theory, 23 conformers were loc ated for FTA, 15 for FME, 9 for FAM, and 11 for FTMA. Electronic correlatio n has been included with the relatively large basis set 6-311G, augmented w ith polarization and diffuse functions, to calculate MP2/6-311++SG**//RHF/G -31G* single-point energies for all the conformers, Frequency analysis and thermochemical calculations have been performed at the RHF/G-31G* level and the results have been utilized to assess gas-phase populations of conforme rs at 298 K for the studied molecules. Moreover, SM5.4 solvation model was used to assess Gibbs free energies of conformers both in water and in chlor oform. The obtained results are compared to those from previous studies of (R,R)-tartaric acid and its derivatives and analyzed in terms of effects of substitution of the hydroxyl group by the fluorine atom. It seems that sub stitution of the OH group by an F atom leads to greater conformational dive rsity of the molecules studied, mainly because the F atom cannot act as a h ydrogen bond donor. From our results, it appears that if hydroxyl groups of (R,R)-tartaric acid are involved in intermolecular interactions, like in c rystals or polar solvents, then the conformational preferences of these com pounds are similar to the conformational preferences of isolated molecules of their dideoxydifluoro analogues.