Last of the gem-Difluorocycloalkanes: Synthesis and Characterization of 2,2-Difluorocyclobutyl-Substituted Building Blocks.
Anton V ChernykhKostiantyn P MelnykovNataliya A TolmachevaIvan S KondratovDmytro S RadchenkoConstantin G DaniliucDmitriy M VolochnyukSergey V RyabukhinYuliya O KuchkovskaOleksandr O GrygorenkoPublished in: The Journal of organic chemistry (2019)
An efficient approach to synthesis of previously unavailable 2-substituted difluorocyclobutane building blocks was developed and applied on a multigram scale. The key step of the synthetic sequence included deoxofluorination of O-protected 2-(hydroxylmethyl)cyclobutanone. Dissociation constants (p Ka) and log P values for 2,2-difluorocyclobutaneamine and 2,2-difluorocyclobutanecarboxylic acid or their derivatives were measured and compared with the values obtained for the corresponding 3,3-difluorocyclobutane derivatives and nonfluorinated counterparts. Three-dimensional structures of 2,2- and 3,3-difluorocyclobutanamines were compared using exit vector plot analysis of X-ray crystallographic data.