Radical‐Promoted Distal C−H Functionalization of C(sp³) Centers with Fluorinated Moieties

Abstract

Due to their unique properties, fluorinated scaffolds are pivotal compounds in pharmaceuticals, agrochemicals, and materials science. Over the last years, the development of versatile strategies for the selective synthesis of fluorinated molecules by direct C−H bond functionalization has attracted a lot of attention. In particular, the design of novel transformations based on a radical process was a bottleneck for distal C−H functionalization reactions, offering synthetic solutions for the selective introduction of fluorinated groups. This Minireview highlights the major contributions in this blossoming field. The development of new methodologies for the remote functionalization of aliphatic derivatives with various fluorinated groups based on a 1,5‐hydrogen atom transfer process and a β‐fragmentation reaction will be showcased and discussed.

Fluorinated triazoles as privileged potential candidates in drug development—focusing on their biological and pharmaceutical properties

“…It has been established that proton substitution by fluorine in heterocycles can produce fruitful pharmacokinetic properties due to enhanced stability and lipophilicity. In addition, fluorine being the most electronegative element, and therefore, the C to F bond is significantly polarized, shows highest ionic character having smaller size compared to other halogens (Nobile et al, 2021). It has been established that replacement of the oxidizable C-H bond by a C-F bond has a key role that enhances the biological half-life of a drug thereby increasing its metabolic stability (Yadav et al, 2018).…”

Remote Fluorination of α,β‐Unsaturated Carbonyls via Silyl Dienol Ethers

“…Existing strategies granting access to remotely fluorinated carbonyls include visible light photoirradiation of steroids, [4] 1,5‐HAT processes, [5] and metal‐mediated ring‐opening of cyclobutanols, [6] which suffer from substantial substrate limitations. Hydrofluoro‐methylation of alkenes has been utilized to access γ‐fluoro carbonyls as well, [7] however, this involves C−C bond formation as opposed to C−F bond formation, leading to limitations from a diversification standpoint.…”

Remote Fluorination of α,β-Unsaturated Carbonyls via Silyl Dienol Ethers

“…Hence, methods that incorporate fluorine or fluoroalkyl groups at the remote γ-site are of great synthetic value (Scheme 1a). [3] Existing strategies granting access to remotely fluorinated carbonyls include visible light photoirradiation of steroids, [4] 1,5-HAT process, [ 5 ] and metal-mediated ring-opening of cyclobutanols, [ 6 ] which suffer from substantial substrate limitations. Hydrofluoro-methylation of alkenes has been utilized to access γ-fluoro carbonyls as well, [7] however, this involves C-C bond formation as opposed to C-F bond formation, leading to limitations from a diversification standpoint.…”