Abstract
Background: Since trifluoromethyl-containing compounds have found diverse applications in the fields of pharmaceuticals and agrochemicals, facile and selective synthetic methods for trifluoromethyl-substituted compounds are an essential tool for advanced medicinal chemistry. Now that diverse synthetic transformations of carbon–carbon triple bonds are available, 3,3,3-trifluoropropynyl-substituted compounds serve as versatile building blocks for target molecules containing trifluoromethyl groups. Thus, novel synthetic methods and reagents for incorporation of a 3,3,3-trifluoropropynyl group into an organic compound have been the major concern in exploration and modification of fluorine-based biologically active substances. Results & discussion: We report a preparative method of 3,3,3-trifluoropropynyllithium and its reaction with electrophiles including aldehydes, ketones, trimethoxyborane, chlorosilanes and chlorostannanes in detail. Palladium-catalyzed synthetic reactions of the carbonyl adducts and the trifluoromethyl-containing metalloid reagents are also demonstrated, which provide simple synthetic methods of trifluoromethylated allenes, arylacetylenes and enynes. The synthetic transformations presented here expand the repertoire of trifluoromethylated compounds available for medicinal scientists and contribute to the advance of future medicinal chemistry.
Acknowledgements
The authors thank Central Glass Co Ltd. for the generous gift of 1,1-dichloro-3,3,3-trifluoroacetone.
Financial & competing interests disclosure
This work was supported by a Grant-in-Aid for Creative Scientific Research, No 16GS0209, from Ministry of Education, Culture, Sports, Science and Technology, Japan. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.
Ethical conduct of research
The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.