The vicinal difluoro motif in organic chemistry : the synthesis and behaviour of compounds derived from 2,3-diflurosuccinic acids

Organofluorine compounds--Synthesis;Organofluorine compounds

Schueler, Martin ; O'Hagan, David ; O'Hagan, David

University:University of St Andrews

Department:Chemistry (School of)

关键词: Organofluorine compounds--Synthesis;    Organofluorine compounds;   

Others  :  https://research-repository.st-andrews.ac.uk/bitstream/handle/10023/2632/MartinSchuelerPhDThesis.pdf?sequence=3&isAllowed=y

来源: DR-NTU

【 摘 要 】

The following work describes the synthesis of compounds carrying a vicinal difluoromotif and the evaluation of this structural element to influence the conformation oforganic molecules. The synthesis of erythro and threo 1,2-difluoro-1,2-diphenylethanewas achieved by bromofluorination and subsequent halogen exchange from stilbene.Oxidative degradation of the phenyl rings allowed to access erythro and threo 2,3-difluorosuccinic acids and a variety of derivatives thereof. The conformations of thesecompounds were investigated by means of X-ray analysis and NMR spectroscopy.Conformational analysis of derivatives of 2,3-difluorosuccinic acid was carried outusing JHFandJHHNMR coupling constants. A clear preference for the conformations inwhich the two vicinal C-F bonds are gauche emerged from these calculations, whichwas confirmed by temperature and solvent dependent NMR analyses.The vicinal difluoro motif was incorporated into small peptide structures. In the solidstate, a strong preference to align the vicinal C-F bonds gauche to each other wasobserved and when adjacent to an amide moiety, the C-F bond was found to prefer ananti periplanar orientation with respect to the carbonyl bond. These effects appeared tooverride steric and electrostatic interactions. The conformation of these fluorinecontainingpeptides showed a clear dependence on the stereochemicaol rientation of theC-F bonds, and this appears to be an effective tool for influencing the secondary andconsequently tertiary structure in a predictable manner. In order to access singleenantiomerso f peptides having the vicinal difluoro, motif, a stereoselectiver oute to R,Rand SS 2,3-difluorosuccinic was developed. This involved nucleophilic fluorination ofthe cyclic sulfates generated from (R, R)- and (SS)- diethyl tartrates and subsequentdeoxofluorination of the intermediate fluorohydrins.