Controlled oligomerization of [1.1.1]propellane through radical polarity matching: selective synthesis of SF- and CFSF-containing [2]staffanes.

Selectivity in radical chain oligomerizations involving [1.1.1]propellane - i.

Overcoming a Radical Polarity Mismatch in Strain-Release Pentafluorosulfanylation of [1.1.0]Bicyclobutanes: An Entryway to Sulfone- and Carbonyl-Containing SF-Cyclobutanes.

The first assortment of achiral pentafluorosulfanylated cyclobutanes (SF-CBs) are now synthetically accessible through strain-release functionalization of [1.1.0]bicyclobutanes (BCBs) using SFCl.

Competition between C-C and C-H Bond Fluorination: A Continuum of Electron Transfer and Hydrogen Atom Transfer Mechanisms.

In 2015, we reported a photochemical method for directed C-C bond cleavage/radical fluorination of relatively unstrained cyclic acetals using Selectfluor and catalytic 9-fluorenone. Herein, we provide a detailed mechanistic study of this reaction, during which it was discovered that the key electron transfer step proceeds through substrate oxidation from a Selectfluor-derived -centered radical intermediate (rather than through initially suspected photoinduced electron transfer). This finding led to proof of concept for two new methodologies, demonstrating that unstrained C-C bond fluorination can also be achieved under chemical and electrochemical conditions.

Strain-Release Pentafluorosulfanylation and Tetrafluoro(aryl)sulfanylation of [1.1.1]Propellane: Reactivity and Structural Insight.

We leveraged the recent increase in synthetic accessibility of SF Cl and Ar-SF Cl compounds to combine chemistry of the SF and SF Ar groups with strain-release functionalization. By effectively adding SF and SF Ar radicals across [1.1.

Evidence for C-F Bond Formation through Formal Reductive Elimination from Tellurium(VI).

The fundamental challenge of C-F bond formation by reductive elimination has been met by compounds of select transition metals and fewer main group elements. The work detailed herein expands the list of main group elements known to be capable of reductively eliminating a C-F bond to include tellurium. Surprising and novel modes of both sp and sp C-F bond formation were observed alongside formation of Te cations during two separate attempts to synthesize/characterize fluorinated organotellurium(VI) cations in superacidic media (SbF /SO ClF).

Oxidative Fluorination of Heteroatoms Enabled by Trichloroisocyanuric Acid and Potassium Fluoride.

In synthetic method development, the most rewarding path is seldom a straight line. While our initial entry into pentafluorosulfanyl (SF ) chemistry did not go according to plan (due to inaccessibility of reagents such as SF Cl at the time), a "detour" led us to establish mild and inexpensive oxidative fluorination conditions that made aryl-SF compound synthesis more accessible. The method involved the use of potassium fluoride and trichloroisocyanuric acid (TCICA)-a common swimming pool disinfectant-as opposed to previously employed reagents such as F , XeF , HF, and Cl .

Structural proof of a [C-F-C] fluoronium cation.

Organic fluoronium ions can be described as positively charged molecules in which the most electronegative and least polarizable element fluorine engages in two partially covalent bonding interactions to two carbon centers. While recent solvolysis experiments and NMR spectroscopic studies on a metastable [C-F-C] fluoronium ion strongly support the divalent fluoronium structure over the alternative rapidly equilibrating classical carbocation, the model system has, to date, eluded crystallographic analysis to confirm this phenomenon in the solid state. Herein, we report the single crystal structure of a symmetrical [C-F-C] fluoronium cation.

The Supramolecular Structural Chemistry of Pentafluorosulfanyl and Tetrafluorosulfanylene Compounds.

The analysis of crystal structures of SF - or SF -containing molecules revealed that these groups are often surrounded by hydrogen or other fluorine atoms. Even though fluorine prefers F⋅⋅⋅H over F⋅⋅⋅F contacts, the latter appeared to be important in many compounds. In a significant number of datasets, the closest F⋅⋅⋅F contacts are below 95 % of the van der Waals distance of two F atoms.

Ideality in Context: Motivations for Total Synthesis.

Total synthesis-the ultimate proving ground for the invention and field-testing of new methods, exploration of disruptive strategies, final structure confirmation, and empowerment of medicinal chemistry on natural products-is one of the oldest and most enduring subfields of organic chemistry. In the early days of this field, its sole emphasis focused on debunking the concept of vitalism, that living organisms could create forms of matter accessible only to them. Emphasis then turned to the use of synthesis to degrade and reconstitute natural products to establish structure and answer questions about biosynthesis.

Deoxygenative Fluorination of Phosphine Oxides: A General Route to Fluorinated Organophosphorus(V) Compounds and Beyond.

Fluorinated organophosphorus(V) compounds are a very versatile class of compounds, but the synthetic methods available to make them bear the disadvantages of 1) occasional handling of toxic or pyrophoric P starting materials and 2) a dependence on hazardous fluorinating reagents such as XeF . Herein, we present a simple solution and introduce a deoxygenative fluorination (DOF) approach that utilizes easy-to-handle phosphine oxides as starting materials and effectively replaces harsh fluorinating reagents by a combination of oxalyl chloride and potassium fluoride. The reaction has proven to be general, as R PF , R PF , and RPF compounds (as well as various cations and anions derived from these) are accessible in good yields and on up to a multi-gram scale.

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.

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.

Quest for a Symmetric [C-F-C] Fluoronium Ion in Solution: A Winding Path to Ultimate Success.

In this Account, we chronicle our tortuous but ultimately fruitful quest to synthesize a [C-F-C] fluoronium ion in solution, thus providing the last piece of the organic halonium ion puzzle. Inspiration for the project can be traced all the way back to the graduate career of the corresponding author, wherein the analogy between a [C-H-C]+ "hydrido" bridge and a hypothetical [C-F-C] bridge was first noted. The earliest attempt to construct a bicyclo[5.

Difluoro(aryl)(perfluoroalkyl)-λ -sulfanes and Selanes: Missing Links of Trichloroisocyanuric Acid/Potassium Fluoride Chemistry.

The TCICA/KF approach to oxidative fluorination of heteroatoms has emerged as a surprisingly simple, safe, and versatile surrogate to classically challenging fluorination reactions. Although polyfluorination (or chlorofluorination) of diaryl disulfides, diaryl diselenides, diaryl ditellurides, aryl iodides, and aryl(perfluoroalkyl)tellanes has been described, the application of this TCICA/KF methodology to aryl(perfluoroalkyl)sulfanes and selanes remains an area of unexplored chemical space. Accordingly, to address the "missing links" in the developing series of chalcogen-based substrate reactivity, we report mild syntheses of metastable difluoro(aryl)(perfluoroalkyl)-λ -sulfanes and selanes.

Substituent-controlled, mild oxidative fluorination of iodoarenes: synthesis and structural study of aryl I(iii)- and I(v)-fluorides.

We report a mild approach to the synthesis of difluoro(aryl)-λ-iodanes (aryl-IF compounds) and tetrafluoro(aryl)-λ-iodanes (aryl-IF compounds) using trichloroisocyanuric acid (TCICA) and potassium fluoride (KF). Under these reaction conditions, selective access to either the I(iii)- or I(v)-derivatives is predictable based solely on the substitution pattern of the iodoarene starting material. Moreover, the discovery of this TCICA/KF approach prompted detailed dynamic NMR, kinetic, computational, and crystallographic studies on the relationship between the IF group and the -substituents on carefully designed probe molecules.

Observation of the dipole- and quadrupole-bound anions of 1,4-dicyanocyclohexane.

Quadrupole-bound anions are negative ions in which their excess electrons are loosely bound by long-range electron-quadrupole attractions. Experimental evidence for quadrupole-bound anions has been scarce; until now, only trans-succinonitrile had been experimentally confirmed to form a quadrupole-bound anion. In this study, we present experimental evidence for a new quadrupole-bound anion.

Pentafluoro(aryl)-λ -tellanes and Tetrafluoro(aryl)(trifluoromethyl)-λ -tellanes: From SF to the TeF and TeF CF Groups.

The TeF group is significantly underexplored as a highly fluorinated substituent on an organic framework, despite it being a larger congener of the acclaimed SF group. In fact, only one aryl-TeF compound (phenyl-TeF ) has been reported to date, synthesized using XeF . Our recently developed mild TCICA/KF approach to oxidative fluorination provides an affordable and scalable alternative to XeF .

Making the SF Group More Accessible: A Gas-Reagent-Free Approach to Aryl Tetrafluoro-λ -sulfanyl Chlorides.

Modern pentafluorosulfanyl (SF ) chemistry has an Achilles heel: synthetic accessibility. Herein, we present the first approach to aryl-SF Cl compounds (key intermediates in state-of-the-art aryl-SF synthesis) that overcomes the reliance on hazardous fluorinating reagents and/or gas reagents (e.g.

Determining the predominant tautomeric structure of iodine-based group-transfer reagents by O NMR spectroscopy.

Cyclic benziodoxole systems have become a premier scaffold for the design of electrophilic transfer reagents. A particularly intriguing aspect is the fundamental I-I tautomerism about the hypervalent bond, which has led in certain cases to a surprising re-evaluation of the classic hypervalent structure. Thus, through a combination of O NMR spectroscopy at natural abundance with DFT calculations, we establish a convenient method to provide solution-phase structural insights for this class of ubiquitous reagents.

Catalyzed and Promoted Aliphatic Fluorination.

In the last six years, the direct functionalization of aliphatic C-H (and C-C) bonds through user-friendly, radical-based fluorination reactions has emerged as an exciting research area in fluorine chemistry. Considering the historical narratives about the challenges of developing practical radical fluorination in organic frameworks, notable advancements in controlling both reactivity and selectivity have been achieved during this time. As one of the participants in the field, herein, we a provide brief account of research efforts in our laboratory from the initial discovery of radical monofluorination on unactivated C-H bonds in 2012 to more useful strategies to install fluorine on biologically relevant molecules through directed fluorination methods.

Spectroscopic Characterization of a [C-F-C] Fluoronium Ion in Solution.

We report the first spectroscopic evidence for a [C-F-C] fluoronium ion in solution. Extensive NMR studies ( F, H, C) characterize a symmetric cage-like species in which fluorine exhibits substantial covalent bonding to each of the two carbon atoms involved in the three-center interaction. Experimental NMR data comport well with calculated values to lend credence to the structural assignment.

Sensitized Aliphatic Fluorination Directed by Terpenoidal Enones: A "Visible Light" Approach.

In our continued effort to address the challenges of selective sp C-H fluorination on complex molecules, we report a sensitized aliphatic fluorination directed by terpenoidal enones using catalytic benzil and visible light (white LEDs). This sensitized approach is mild, simple to set up, and an economical alternative to our previous protocol based on direct excitation using UV light in a specialized apparatus. Additionally, the amenability of this protocol to photochemical flow conditions and preliminary evidence for electron-transfer processes are 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.

Fluorine in a C-F Bond as the Key to Cage Formation.

Cage molecules have long been employed to trap reactive or transient species, as their rigid nature allows them to enforce situations that otherwise would not persist. In this Minireview, we discuss our use of rigid cage structures to investigate the close noncovalent interactions of fluorine with other functional groups and determine how mutual proximity affects both physical properties and reactivity. Unusual covalent interactions of fluorine are also explored: the cage can close to form the first solution-phase C-F-C fluoronium ion.

Through-Space Activation Can Override Substituent Effects in Electrophilic Aromatic Substitution.

Electrophilic aromatic substitution (EAS) represents one of the most important classes of reactions in all of chemistry. One of the "iron laws" of EAS is that an electron-rich aromatic ring will react more rapidly than an electron-poor ring with suitable electrophiles. In this report, we present unique examples of electron-deficient arenes instead undergoing preferential substitution in intramolecular competition with more electron-rich rings.