Recent Advances in C—F Bond Formation from Carbon‐Centered Radicals

Comprehensive Summary Construction of C—F bonds is a direct and efficient method for introducing fluorine into pharmaceuticals, agrochemicals, and materials. Strategies such as nucleophilic, electrophilic, radical, and transition‐metal catalyzed fluorination have been developed to meet the demand of diverse C—F bond formation. Among them, radical fluorination has been witnessed with substantial advancement in a recent decade. Herein, we reviewed methods for formation of C—F bonds with carbon‐centered radicals as key intermediates, especially in recent five years. We introduce in the paper with different fluorinating reagents, strategies for radical generation, and application in late‐stage functionalization and synthesis of PET tracers. We also indicate the current limitations and propose the direction of the field for the future development. Key Scientists Radical fluorination was recognized as an old and uncontrolled reaction that may date back to the time when element fluorine was first mixed with organic compounds by Henri Moissan in 1891. The development of the field was slow in combination with discovery of new fluorinating reagents. Substantial changes took place in 2012, when the first example of carbon radical fluorination with robust and mild fluorinating reagents, such as NFSI and Selectfluor, was reported by the Sammis group. In the same year, Groves, Lectka, Li, and Boger led the pioneering works on aliphatic C—H fluorination, decarboxylative fluorination, and fluorofunctionalization of alkenes in a radical manner. Photoredox catalysis was introduced to radical fluorination in 2013 by the Chen group, which opens up a new avenue for diverse fluorinative transformations. Most of the previous works focus on radical fluorination to form C(sp 3 )–F bonds. In 2018, the challenging non‐directed aromatic C—H fluorination was solved by Ritter and coworkers. Direct arene fluorination with fluoride ion was later disclosed by the Nicewicz group in 2019. There are many other scientists that have also made tremendous contribution to the development of radical fluorination, with too limited space to list them all. We only list those with first discoveries that may point to the new direction of radical fluorination.