Science of Synthesis

Champagne, P. A.; Drouin, M.; Paquin, J.-F., Science of Synthesis Knowledge Updates, (2016) 1, 419.

With the recent interest in C—H activation strategies, which stem from the simplicity of using unfunctionalized substrates to generate interesting products, C—H fluorination has appeared as a powerful method to obtain benzylic fluorides. The simplest examples are of electrophilic fluorination α to an electron-withdrawing group. While the strategy has been known for some time, enantioselective variations have been developed in the last decade, starting with Sodeoka’s 2002 paper on the catalytic fluorination of β-oxo esters.[‌1‌] Since 2005, this methodology has been extended to access enantioenriched benzylic fluorides α to an electron-withdrawing group. Another type of transformation includes radical processes, which are applicable to diverse substrates, since C—H bonds at benzylic positions are more reactive than other C(sp3)—H bonds. These reactions can be initiated using metals, photocatalysts, or free-radical initiators. Finally, dehydrofluorination can be carried out using transition-metal catalysis; however, for these reactions, complex directing groups are still necessary to obtain regioselective transformations.

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