Synthesis of a Hominal Bis(difluoromethyl) Fragments

This paper describes the synthesis of discrete units of hominal bis(gem-CF2). The controlled introduction of fluorine atoms is a powerful synthetic tool to introduce dipole moments with minimal impact to sterics. Polyvinylidene fluoride (PVDF) is a striking example of the influence of fluorine atoms, which impart ferroelectric behavior from the alignment of the dipole moments of CF2 units, however, it is prepared via direct polymerization of vinylidene difluoride. Thus, a different synthetic pathway is required to produce synthons containing discrete numbers of CF2 groups in a hominal relation to each other. We found out that, in the case of short chains, the consecutive deoxofluorination of sequentially-introduced keto groups is very inefficient, as it requires harsh conditions and sharply decreasing yields at each step. To solve this problem, we combined the selective desulfurative fluorination of dithiolanes with pyridinium fluoride and the deoxofluorination of keto groups with morpholinosulfur trifluoride. This strategy is highly reproducible and scalable, allowing the synthesis of the hominal bis(gem-CF2) fragment as a shelf-stable tosylate, which can be used to install discrete chains of hominal bis(gem-CF2) on a variety of synthons and monomers.