Ligand‐Assisted Palladium(II)/(IV) Oxidation for sp³ CH Fluorination

Abstract

Thed irect functionalization of inert sp 3 C À Hb onds is limited to afew bond types. Although the activation of sp 3 C À Hb onds can be accomplished under mild conditions using palladium catalysts,t he subsequent functionalization is not trivial due to the high energy required to convert palladium(II) to palladium(IV). We have systematicallys tudied the palladium oxidation using computation-guided experiments for reactions involving strong chelation control. We find that amild external ligand could significantly accelerate the oxidation of palladium(II) to palladium(IV) for strong bidentated irecting groups. Thea ccelerationi sb elieved to be ar esult of ligand stabilization of both the palladium(II) and palladium(IV)intermediates.

A comprehensive overview of directing groups applied in metal-catalysed C–H functionalisation chemistry

“…In addition, to the reports from Yu 496 and Shi 497 who investigated the Pd-catalysed fluorination of amino acid derivatives at the β-position with other DGs, the Pd-catalysed directed fluorination of unactivated aliphatic chains with this bidentate DG was studied by the groups of Xu ( Scheme 82B ) 498 as well as Wu, Zhang and Huang ( Scheme 82C ). 499 In both cases, an electrophilic fluorinated reagent was used and a Pd( ii )/Pd( iv ) process was proposed to promote the reductive elimination step in this challenging transformation.…”

The Fluorination of C−H Bonds: Developments and Perspectives

“…In addition, the monodentate directing group leaves a vacant coordination site on palladium, that can be occupied by external ligands. [59] Indeed, the effect of the ligand is stark, considering the fluorinated phenylalanine derivative is obtained in 83% yield in the presence of 10 mol% of the quinoline ligand, while no product is observed in its absence. A range of N-phthaloyl α-amino acid derivatives underwent fluorination with excellent diastereoselectivity.…”

“…However, in Yu's procedure, the acidic amide is only a weak coordinator to palladium. In addition, the monodentate directing group leaves a vacant coordination site on palladium, which can be occupied by external ligands . Indeed, the effect of the ligand is significant, considering that the fluorinated phenylalanine derivative is obtained in 83 % yield in the presence of 10 mol % of the quinoline ligand, while no product is observed in its absence.…”

Fluorierung von C‐H‐Bindungen: Entwicklungen und Perspektiven

“…In der Vorschrift von Yu et al hingegen koordiniert das saure Amid nur schwach an das Palladiumzentrum, und die einzähnige dirigierende Gruppe çffnet eine freie Koordinationsstelle am Pd-Zentrum, die von externen Liganden besetzt werden kann. [61] In Anbetracht der Tatsache,dass das fluorierte Phenylalaninderivat in 83 %Ausbeute in Gegenwart von 10 mol %d es Chinolinliganden entsteht, während bei dessen Fehlen kein Produkt resultiert, kann der Effekt des Liganden als signifikant bezeichnet werden. Eine Schema 14. a) Kupferkatalysierte C-H-Radiofluorierungmit K 18 F, wie von Sanford und Mitarbeitern verçffentlicht.…”