Site‐Selective Approach to β‐Fluorination: Photocatalyzed Ring Opening of Cyclopropanols

Abstract

To expand upon the recent pioneering reports of catalyzed sp(3) C-H fluorination methods, the next rational step is to focus on directing "radical-based fluorination" more effectively. One potential solution entails selective C-C bond activation as a prelude to selective fluorination. Herein, we report the tandem photocatalyzed ring-opening/fluorination reactions of cyclopropanols by 1,2,4,5-tetracyanobenzene (TCB) and Selectfluor to afford a process tantamount to site-selective β-fluorination of carbonyl-containing compounds. This new approach provides a synthetically mild and operationally simple route to otherwise difficult-to-prepare β-fluorinated products in good yields and with good-to-excellent regioselectivity. Remarkably, substrates that contain other usually reactive (e.g., benzylic) sites undergo ring-opening fluorination preferably. The versatility of this method to give cyclic β-fluorides from tertiary cyclopropanols and γ-fluoro alcohols is also highlighted.

Radical‐Promoted C−C Bond Cleavage: A Deconstructive Approach for Selective Functionalization

“…Photocatalyzed processes have recently emerged as an alternative for the generation of alkoxy radicals by using milder reaction conditions, thus avoiding undesired side‐reactions . In 2015, the group of Leckta disclosed the first deconstruction/fluorination of cyclopropanols in the presence of a photooxidant (PO). The radical cation generated under these conditions is able to induce a C−C bond elongation (Scheme ), the thermodynamic driving force for the photolytic homolysis.…”

Radical‐Promoted C−C Bond Cleavage: A Deconstructive Approach for Selective Functionalization

“…[29] In 2015, the group of Leckta [30] disclosed the first deconstruction/fluorination of cyclopropanols in the presence of ap hotooxidant (PO). [29] In 2015, the group of Leckta [30] disclosed the first deconstruction/fluorination of cyclopropanols in the presence of ap hotooxidant (PO).…”

“…Photocatalyzed processes have recently emerged as an alternative for the generation of alkoxy radicals by using milder reaction conditions,t hus avoiding undesired sidereactions. [29] In 2015, the group of Leckta [30] disclosed the first deconstruction/fluorination of cyclopropanols in the presence of ap hotooxidant (PO). Ther adical cation generated under these conditions is able to induce aC À Cb ond elongation (Scheme 6), the thermodynamic driving force for the photolytic homolysis.I n2 016, the group of Chen [31] developed ac omplementary strategy to generate alkoxy radicals by using cyclic iodine(III) reagent (CIR) catalysis.T he elementary step of this transformation resembles Suµrezschemistry, but here the authors used aC IR/photoredox dual-catalytic system for the generation of an alkoxy radical under milder reaction conditions.D espite these achievements,t hese catalytic photoinduced approaches are only used with strained cycloalkanols.…”

β-Scission of Alkoxy Radicals in Synthetic Transformations

“…Lectka reported photoredox-mediated ring-opening fluorination of cyclopropanols (Scheme 19). 34 β-Fluoro ketone 67 is produced when an acetonitrile solution containing cyclopropanol 66, 1,2,4,5-tetracyanobenzene (TCB), and Selectfluorμ is irradiated with UV light. Mechanistically, TCB serves as the photoredox catalyst to mediate single electron oxidation of 66, and the resulting alkoxy radical intermediate undergoes β-scission (ring opening).…”