This Review summarizes the advances in fluorination via C(sp 2)-H and C(sp 3)-H activation. Transition metal catalyzed approaches championed by palladium have allowed the installation of a fluorine substituent at C(sp 2) and C(sp 3) sites exploiting the reactivity of high oxidation transition metal fluoride complexes combined with the use of directing group (some transient) to control regio-and stereoselectivity. The large majority of known methods employ electrophilic fluorination reagents, but methods combining a nucleophilic fluoride source with an oxidant have appeared. A number of ligands have proven to be effective for C(sp 3)-H fluorination directed by weakly coordinating auxiliaries, thereby enabling control over reactivity and selectivity. Methods relying on the formation of radical intermediates are complementary to transition metal catalyzed processes as they allow for undirected C(sp 3)-H fluorination. To date, radical C-H fluorinations mainly employ electrophilic N-F fluorination reagents but a unique bio-inspired Mn(III)-catalyzed oxidative C-H fluorination has been developed. Overall, the field of late stage nucleophilic C-H fluorination has progressed much more slowly, a state of play explaining why C-H 18 F-fluorination is still in its infancy. C-F reductive elimination C(sp 2)-H C(sp 3)-H C(sp 3)-H

The past few decades have seen tremendous progress in the synthesis and operation of molecular systems capable of controlled mechanical movement. Here we review the use of molecular machines as catalysts for controlling chemical reactions. We highlight the various catalyst designs with a focus on how the mechanical motion is used to control catalysis with varying degrees of success. This review discusses the current challenges of designing effective catalysts, the scope and limitations of various systems, as well as future potential and aims for the field. Although it is difficult to predict which concepts will become most important as so much work is at the proof of concept level, it seems clear that molecular machines have the potential to significantly impact the field of catalysis.We present an overview of innovations in using molecular machines as catalysts and discuss the concepts and principles emerging from the field. It is apparent that selectivity is a key challenge. 14 Perfectly selective switching of devices between 'on/off' states or between distinct catalytic functions has proven difficult to achieve. As with all catalysis, product chemo-and stereo-selectivity is also challenging. In addition, molecular machines must deal with kinetic factors that may Molecular machine: a system in which a stimulus triggers the controlled motion of one molecular or submolecular component relative to another and potentially results in a net task (or work) being done. 7 Chemoselectivity:The preferential reaction of one functional group over another in a chemical reaction. 15 Stereoselectivity:The preferential formation of one stereoisomer over another in a chemical reaction. If the stereoisomers are enantiomers, enantioselectivity applies (quantified by enantiomeric excess, e.e., or enantiomeric ratio, e.r.), if they are diastereomers, diastereoselectivity applies (quantified by diasteriomeric ratio, d.r.). 16

Protein–carbohydrate interactions are implicated in many biochemical/biological processes that are fundamental to life and to human health. Fluorinated carbohydrate analogues play an important role in the study of these interactions and find application as probes in chemical biology and as drugs/diagnostics in medicine. The availability and/or efficient synthesis of a wide variety of fluorinated carbohydrates is thus of great interest. Here, we report a detailed study on the synthesis of monosaccharides in which the hydroxy groups at their 4- and 6-positions are replaced by all possible mono- and difluorinated motifs. Minimization of protecting group use was a key aim. It was found that introducing electronegative substituents, either as protecting groups or as deoxygenation intermediates, was generally beneficial for increasing deoxyfluorination yields. A detailed structural study of this set of analogues demonstrated that dideoxygenation/fluorination at the 4,6-positions caused very little distortion both in the solid state and in aqueous solution. Unexpected trends in α/β anomeric ratios were identified. Increasing fluorine content always increased the α/β ratio, with very little difference between regio- or stereoisomers, except when 4,6-difluorinated.

Herein, we report a highly effective protocol for the cross-coupling of (hetero)aryl bromides with fluorinated alcohols using the commercially available precatalyst t BuBrettPhos Pd G3 and Cs 2 CO 3 in toluene. This Pd-catalyzed coupling features a short reaction time, excellent functional group tolerance, and compatibility with electron-rich and -poor (hetero)arenes. The method provides access to 18 F-labeled trifluoroethyl ethers by cross-coupling with [ 18 F]trifluoroethanol.

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The diastereoselective synthesis of fluorinated building blocks that contain chiral fluorine substituents is of interest. Here we describe optimisation efforts in the synthesis of anti-2,3-difluorobutane-1,4-diol, as well as the synthesis of the corresponding syn-diastereomer. Both targets were synthesised using an epoxide opening strategy.

This Review summarizes the advances in fluorination via C(sp 2)-H and C(sp 3)-H activation. Transition metal catalyzed approaches championed by palladium have allowed the installation of a fluorine substituent at C(sp 2) and C(sp 3) sites exploiting the reactivity of high oxidation transition metal fluoride complexes combined with the use of directing group (some transient) to control regio-and stereoselectivity. The large majority of known methods employ electrophilic fluorination reagents, but methods combining a nucleophilic fluoride source with an oxidant have appeared. A number of ligands have proven to be effective for C(sp 3)-H fluorination directed by weakly coordinating auxiliaries, thereby enabling control over reactivity and selectivity. Methods relying on the formation of radical intermediates are complementary to transition metal catalyzed processes as they allow for undirected C(sp 3)-H fluorination. To date, radical C-H fluorinations mainly employ electrophilic N-F fluorination reagents but a unique bio-inspired Mn(III)-catalyzed oxidative C-H fluorination has been developed. Overall, the field of late stage nucleophilic C-H fluorination has progressed much more slowly, a state of play explaining why C-H 18 F-fluorination is still in its infancy. C-F reductive elimination C(sp 2)-H C(sp 3)-H C(sp 3)-H

No abstract