Spectroscopic and Crystallographic Characterization of the R N -C-H⋅⋅⋅X Interaction.

As appreciation for nonclassical hydrogen bonds has progressively increased, so have efforts to characterize these interesting interactions. Whereas several kinds of C-H hydrogen bonds have been well-studied, much less is known about the R N -C-H⋅⋅⋅X variety. Herein, we present crystallographic and spectroscopic evidence for the existence of these interactions, with special relevance to Selectfluor chemistry.

Acetyl nitrate mediated conversion of methyl ketones to diverse carboxylic acid derivatives.

The development of a novel acetyl nitrate mediated oxidative conversion of methyl ketones to carboxylic acid derivatives is described. By analogy to the haloform reaction and supported by experimental and computational investigation we propose a mechanism for this transformation.

Arene Amination Instead of Fluorination: Substitution Pattern Governs the Reactivity of Dialkoxybenzenes with Selectfluor.

Arene substitution patterns are well-known to affect the regioselectivity of a given transformation but not necessarily the type of reactivity. Herein, we report that the substitution pattern of alkoxyarenes dictates whether a putative one-electron or two-electron reaction predominates in reactions with Selectfluor. A series of amination products is presented, resulting from the single-electron oxidation of electron-rich arenes followed by direct C-H to C-N bond formation.

Cooperative Noncovalent Interactions Lead to a Highly Diastereoselective Sulfonyl-Directed Fluorination of Steroidal α,β-Unsaturated Hydrazones.

A series of steroidal α,β-unsaturated hydrazones is presented whose behavior and reactivity are governed by various types of weak C-H hydrogen bonds. Several interesting features in a representative X-ray crystal structure and H NMR spectrum are examined that provide evidence for a unique bifurcated intramolecular C-H interaction. Moreover, these steroid derivatives undergo functionalization in the form of a highly regio- and stereoselective fluorination; the sulfonyl oxygen atoms are proposed to direct the fluorinating reagent through C-H hydrogen bonds.

Carbonyl-Directed Aliphatic Fluorination: A Special Type of Hydrogen Atom Transfer Beats Out Norrish II.

Recently, our group reported that enone and ketone functional groups, upon photoexcitation, can direct site-selective sp C-H fluorination in terpenoid derivatives. How this transformation actually occurred remained mysterious, as a significant number of mechanistic possibilities came to mind. Herein, we report a comprehensive study describing the reaction mechanism through kinetic studies, isotope-labeling experiments, F NMR, electrochemical studies, synthetic probes, and computational experiments.

Light-controlled twister ribozyme with single-molecule detection resolves RNA function in time and space.

Small ribozymes such as twister spontaneously cleave their own RNA when the ribozyme folds into its active conformation. The coupling between twister folding and self-cleavage has been difficult to study, however, because the active ribozyme rapidly converts to product. Here, we describe the synthesis of a photocaged nucleotide that releases guanosine within microseconds upon photosolvolysis with blue light.

Site-Selective Photochemical Fluorination of Ketals: Unanticipated Outcomes in Selectivity and Stability.

We report a method for the regioselective photochemical sp C-H fluorination of acetonide ketals that presents interesting problems in chemical reactivity. The question of why certain products of the reaction are stable while others are not is addressed, as is the question of why only select α-ethereal hydrogen atoms are targeted in the reaction. We demonstrate that the method can be employed to synthesize unprecedented fluorinated sugars and steroids, and it can also be applied toward the fluorination of carbamates.

Fluorofunctionalization of C═C Bonds with Selectfluor: Synthesis of β-Fluoropiperazines through a Substrate-Guided Reactivity Switch.

The halofunctionalization of alkene substrates remains an essential tool for synthetic chemists. Herein, we report regioselective ammoniofluorination of unactivated alkenes through photochemical means. A one-pot transformation of the ammonium fluoride products into pharmaceutically relevant β-fluoropiperazines is highlighted.

Ketones as directing groups in photocatalytic sp C-H fluorination.

The ubiquitous ketone carbonyl group generally deactivates substrates toward radical-based fluorinations, especially sites closest to it. Herein, ketones are used instead to direct aliphatic fluorination using Selectfluor, catalytic benzil, and visible light. Selective β- and γ-fluorination are demonstrated on rigid mono-, di-, tri-, and tetracyclic (steroidal) substrates employing both cyclic and exocyclic aliphatic ketones as directing groups.

Development of a novel series of non-natural triaryl agonists and antagonists of the Pseudomonas aeruginosa LasR quorum sensing receptor.

Bacterial chemical communication, through a process called quorum sensing (QS), plays a central role in infection in numerous bacterial pathogens. Quorum sensing in Pseudomonas aeruginosa employs a series of small molecule receptors including the master QS regulator, LasR. In this study we investigate a non-natural triaryl series of LasR ligands using a combination of structure activity relationship studies and computational modeling.

Lipoxin A4 augments host defense in sepsis and reduces Pseudomonas aeruginosa virulence through quorum sensing inhibition.

Bacterial infections can quickly turn into sepsis, with its attendant clinical sequelae of inflammation, tissue injury, and organ failure. Paradoxically, sustained inflammation in sepsis may lead to immune suppression, because of which the host is unable to clear the existing infection. Use of agents that suppress the inflammatory response may accelerate host immune suppression, whereas use of traditional antibiotics does not significantly affect inflammation.