We report herein an operationally simple method for the direct conversion of benzylic C–H groups to C–F. We show that visible light can activate diarylketones to abstract a benzylic hydrogen atom selectively. Adding a fluorine radical donor yields the benzylic fluoride and regenerates the catalyst. The selective formation of mono- and difluorination products can be achieved by catalyst-control. 9-Fluorenone catalyzes benzylic C–H monofluorination while xanthone catalyzes benzylic C–H difluorination. The scope and efficiency of this new C–H fluorination method are significantly better than those of the existing methods. This is also the first report of selective C–H gem-difluorination.

To meet their metabolic needs, starved cells first activate autophagy, but activation in parallel of the general amino acid control pathway increases amino acid uptake, leading to reactivation of mTOR and down-regulation of autophagy.

Invasive pathogens interface with the host and its resident microbiota through interkingdom signaling. The bacterial receptor QseC, which is a membrane-bound histidine sensor kinase, responds to the host stress hormones epinephrine and norepinephrine and the bacterial signal AI-3, integrating interkingdom signaling at the biochemical level. Importantly, the QseC signaling cascade is exploited by many bacterial pathogens to promote virulence. Here, we translated this basic science information into development of a potent small molecule inhibitor of QseC, LED209. Extensive structure activity relationship (SAR) studies revealed that LED209 is a potent prodrug that is highly selective for QseC. Its warhead allosterically modifies lysines in QseC, impairing its function and preventing the activation of the virulence program of several Gram-negative pathogens both in vitro and during murine infection. LED209 does not interfere with pathogen growth, possibly leading to a milder evolutionary pressure toward drug resistance. LED209 has desirable pharmacokinetics and does not present toxicity in vitro and in rodents. This is a unique antivirulence approach, with a proven broad-spectrum activity against multiple Gram-negative pathogens that cause mammalian infections.

Aryl and heteroaryl boronic acids and boronate esters are rapidly, often within minutes, transformed into the corresponding phenols by N-oxides in an open flask at ambient temperature. This transformation has broad compatibility with a variety of functional groups.

Metrics & MoreArticle Recommendations CONSPECTUS: Alkenes are ubiquitous in natural products and are extensively used as synthetic feedstocks in multiple fields including organic synthesis, medicinal chemistry, and materials science. Radical-mediated difunctionalization of alkenes provides a powerful tactic for alkene utilization. Despite the considerable progress made in the past several decades, state-of-the-art methods are highly dependent upon activated alkenes in which a proximal group with a π-electron system (e.g., aryl, carbonyl, and heteroatom) is requisite to stabilize the nascent alkyl radical intermediate via p−π conjugation or p orbitals of the heteroatom. In contrast, the transformation of unactivated alkenes, such as aliphatic alkenes, remains challenging.To overcome this obstacle, we have recently disclosed the strategy of intramolecular distal functional group migration (FGM), which has been efficiently applied in radical difunctionalization of unactivated alkenes. A portfolio of functional groups, such as cyano, heteroaryl, oximino, formyl, and alkynyl groups, showcase the excellent migratory aptitude. Mechanistically, after the addition of an extrinsic radical to the alkene, the newly formed active alkyl radical is rapidly captured by the intramolecular migratory group to generate a cyclic intermediate. Subsequent cleavage of the cyclic C−C bond of the intermediate leads to the functionalized product through the FGM process. Based on the strategy of FGM, a set of elusive difunctionalizations of unactivated alkenes have been accomplished (Part A). Alongside this research, an upgraded highly efficient synthetic strategy, "dock-migration," is created for intermolecular difunctionalization of alkenes. A diversity of sulfone-based dual-function reagents are developed. The intermolecular transformation is initiated by docking the dual-function reagent to the alkene, followed by intramolecular migration of the functional group.Compared to the original FGM protocol, the scope of alkenes is significantly extended from the strategically placed tertiary alcoholsubstituted alkenes to general alkenes. Both activated and unactivated alkenes are well tolerated. By this approach, radical-mediated fluoroalkylheteroarylation, fluoroalkylalkynylation, and alkylation of alkenes have been achieved (Part B). Direct elaboration of C−H bonds into the targeted functional groups represents one of the most ideal and straightforward methods for molecular functionalization. The FGM strategy proves to be an ingenious tool for radical-mediated functionalization of remote unactivated C(sp 3 )−H bonds. Based on the FGM process, we have accomplished: (a) remote C(sp 3 )−H heteroarylation and cyanation of unprotected alcohols via the cascade of alkoxy radical-enabled hydrogen atom transfer (HAT) and intramolecular functional group (e.g., heteroaryl, cyano) migration, and (b) distal C(sp 3 )−H vinylation of propargylic alcohols through consecutive alkenyl radical-promoted HAT process and subsequent alkenyl migration (Part C).

A regioselective synthesis of β- and γ-fluorinated ketones via silver-catalyzed ring opening is described. A variety of β- and γ-fluorinated ketones are efficiently prepared, respectively, from tertiary cyclopropanol and cyclobutanol precursors, providing a straightforward approach for the introduction of a fluorine atom into complex molecules. Preliminary mechanistic studies suggest that a radical-mediated sequential C-C bond cleavage and C-F bond formation pathway is involved.

Photoexcited acetophenone can catalyze the fluorination of unactivated C(sp3)–H groups. While acetophenone, a colorless oil, only has a trace amount of absorption in the visible light region, its photoexcitation can be achieved by irradiation with light generated by a household compact fluorescent lamp (CFL). This operational simple method provides improved substrate scope for the direct incorporation of a fluorine atom into simple organic molecules. CFL-irradiation can also be used to promote certain classic UV-promoted photoreactions of colorless monoarylketones and enones/enals.

Reported herein is a novel, useful, visible light-promoted ring-opening functionalization of unstrained cycloalkanols.