Fluorination reactions of medicinal and biologically-active compounds will be discussed. Late stage fluorination strategies of medicinal targets have recently attracted considerable attention on account of the influence that the fluorine atom can impart to targets of medicinal importance, such as a modulation of lipophilicity, electronegativity, basicity and bioavailability, this latter as a consequence of membrane permeability. Therefore, the recourse to late-stage fluorine substitution on compounds with already known and relevant biological activity can provide the pharmaceutical industry with new leads with improved medicinal properties. The fluorination strategies will take into account different fluorinating reagents, nucleophilic, electrophilic and of radical nature. Diverse families of organic compounds such as (hetero)aromatic rings, and aliphatic substrates (sp 3 , sp 2 , and sp carbon atoms) will be studied in late-stage fluorination reaction strategies. The omniphobicity/lipophilicity and electrostatic interactions can be considered among the most prominent effects. Thus, introducing fluorine into an organic compound can significantly alter its biological properties.One other subtle but important effect of introducing fluorine into the backbone of a medicinal target is the inflection of acidity and basicity of the parent compound 4 , which can change, inter alia, the binding affinity, and bioavailability. Highly basic groups can have a detrimental effect on the bioavailability of a drug. Thus introducing a fluorine atom next to a basic group can reduce its basicity, enhancing its membrane permeability, and increasing bioavailability. Although the replacement of hydrogen for fluorine does not have a profound steric influence, electrostatic interactions with other groups can change conformations significantly. The replacement of hydrogen for fluorine on aromatic rings is a well-known strategy to decelerate oxidative metabolic processes by Cytochrome P450 monooxygenases. In this respect, the electron-withdrawing properties of fluorine on aromatic rings, which can slow down hydrolytic metabolism, alter reaction rates and stability of intermediates. Fluorine substitution on aromatic rings is also known to increase binding affinity, as a result of enhancing electrostatic interactions.However, it is difficult to predict the influence of fluorine substitution on the overall profile in a given situation.As numerous reports attest 1 , the number of marketed drugs that contain a fluorine atom has increased rapidly. As of 2009, the FDA-had approved >140 fluorine-containing drugs. This review article is intended to present new synthetic methodologies 9 for accomplishing fluorination reactions on molecules (drugs/prodrugs) with pharmacological activity. It is not our aim (Figure 3). would be beneficial to the syntheses. 3a.-Conversion of C Ar -H into C Ar -F BondsXu and co-workers 38 have developed an ortho C-H bond fluorination of 2-phenoxyl pyridine derivatives through a palladium-catalyzed reaction v...

The relevance of the -CF H moiety has attracted considerable attention from organic synthetic and medicinal chemistry communities, because this group can act as a more lipophilic isostere of the carbinol, thiol, hydroxamic acid, or amide groups. Being weakly acidic, the CF H moiety can establish hydrogen-bonding interactions to improve the binding selectivity of biologically active compounds. Therefore, the hydroxyl, amino, and thio substituents of lead structures are routinely replaced by a CF H motif in drug discovery, with great benefits in the pharmacological activity of drugs and drug candidates and agrochemicals. Consequently, the late-stage introduction of CF H is a sought-after strategy in designing bioactive compounds. Secondly, but nonetheless relevant and meaningful, is the study of synthetic pathways to introduce a CF -Y moiety (Y≠H, F) into organic substrates because compounds that contain a CF -Y functionality have also found vast applications in medicinal chemistry and in other areas, such as that of fungicides, insecticides, etc., and thus, this functionality deserves special attention. Although emphasis is made on difluoromethylation strategies to functionalize different families of organic compounds, three main methodological protocols will be presented in this review article for the late-stage introduction of a CF H or CF Y moieties into organic substrates: i) a metal-photoredox catalysis; ii) through transition metal-catalyzed thermal protocols; and iii) from transition-metal-free strategies.

In this work, we present a room‐ or solar‐light‐initiated transition‐metal‐free radical homolytic aromatic substitution (HAS) reaction of aniline derivatives with perfluoroalkyl moieties employing perfluoroalkyl halides as readily available perfluoroalkyl sources in the presence of cesium carbonate as base and inexpensive Rose Bengal as organophotocatalyst in MeCN as solvent, rendering perfluoroalkyl‐substituted aniline derivatives in good‐to‐excellent yields, even upon scaling up. Although the mechanism of this reaction is still under investigation, we shall present some evidence based on competitive substitution rate experiments that cast some light onto the reaction intermediates.

Advances in visible light-photocatalyzed preparative synthetic organic transformations in water or aqueous media are studied. Both the convenience of visible light photocatalytic strategies to achieve synthetic organic transformations and the employment of water or aqueous mixtures make this approach a very resourceful methodology. Mechanistic aspects for such photocatalyzed processes are discussed. The effects of water in the stereoselectivity of some reactions and considerations regarding the improved enantioselectivity in chiral catalytic photoredox reactions are manifested with the use of water. The use of water as a result of a protocol improvement or environmentally friendlier methodology as compared to the same reaction performed in organic solvents are also considered. All these combined effects of water as a reaction medium or its very presence in photocatalytic reactions have an ultimate goal which is to diminish the environmental impact of synthetic and photocatalytic processes. This perspective highlights the progress and state of the art organic transformations realized by photocatalytic techniques in water or aqueous systems as well as water as a reactant. In this regard, aromatic substitution reactions, radical additions to carbon–carbon double bonds, photooxidation reactions, decarboxylation processes, and miscellaneous reactions are presented.

The use of Zn-phthalocyanine in a red-light-driven process for the perfluoroalkylation reactions of (hetero)arenes and sufides represents a friendlier environmental alternative.

The first perfluoroalkylation reaction of activated arenes (amino-substituted arenes and alkoxyarenes) has been achieved in water by employing the dyad Rose Bengal and hydrosoluble unmodified vitamin B12 (cyanocobalamin) as photocatalyst...

The (TMEDA)I·I3 complex as a new radical initiator for the perfluoroalkylation of RSH.

Radical initiation for the perfluoroalkylation reaction of amino(hetero)aromatics has been accomplished employing the complex [(TMEDA)I$I 3 ] and visible light. This methodology circumvents the use of metal(organo)catalysts and biologically-relevant substrates are easily substituted with R F moieties employing a mild and environmentally benign radical strategy starting from readily-available perfluoroalkyl iodides R F I.