Formation of Strong Boron Lewis Acid Sites on Silica.

Bis(1-methyl-ortho-carboranyl)borane (HBMeoCb2) is a very strong Lewis acid that reacts with the isolated silanols present on silica partially dehydroxylated at 700 °C (SiO2-700) to form the well-defined Lewis site MeoCb2B(OSi≡) (1) and H2. 11B{1H} magic-angle spinning (MAS) nuclear magnetic resonance (NMR) data of 1 are consistent with that of a three-coordinate boron site. Contacting 1 with O═PEt3 (triethylphosphine oxide TEPO) and measuring 31P{1H} MAS NMR spectra show that 1 preserves the strong Lewis acidity of HBMeoCb2. Hydride ion affinity and fluoride ion affinity calculations using small molecules analogs of 1 also support the strong Lewis acidity of the boron sites in this material. Reactions of 1 with Cp2Hf(13CH3)2 show that the Lewis sites are capable of abstracting methide groups from Hf to form [Cp2Hf-13CH3][H313C-B(MeoCb2)OSi≡], but with a low overall efficiency.

Cage hydrocarbons as linkers in dimeric drug design: Case studies with trimethoprim and tedizolid.

The looming threat of a "post-antibiotic era" has been caused by a rapid rise in antibacterial resistance and subsequent depletion of effective antibiotic agents in the clinic. An efficient strategy to address this shortfall lies in the reengineering of pre-existing and commercially available antibiotic drugs. This is exemplified by dimerization, a design concept in which two pharmacophores are covalently linked to form a new chemical entity. The cage hydrocarbons cubane (1), bicyclo[2.2.2]octane (BCO) (2), adamantane (3), and bicyclo[1.1.1]pentane (BCP) (4) present themselves as an attractive family of linkers in this regard. In this report, all four hydrocarbon cages were employed as linkers in a series of dimers based on the commercially available antibiotics trimethoprim and tedizolid. A detailed synthetic roadmap for the protection and deprotection of each pharmacophore is outlined. Several members of the trimethoprim series showed activity on par with that of their trimethoprim progenitor, although this was not the case for the tedizolid series. The design strategy outlined herein highlights the utility of the group as a platform for the rapid and modular construction of future novel antibiotics.

The Effect of Carborane Substituents on the Lewis Acidity of Boranes.

The Lewis acidity of primary, secondary, and tertiary boranes with phenyl, pentafluorophenyl, and all three isomers of the C-substituted icosahedral carboranes (ortho, meta, and para) was investigated by computing their fluoride, hydride, and ammonia affinities as well as their global electrophilicity indices and LUMO energies. From these calculations, it was determined that the substituent effects on the Lewis acidity of these boranes follow the trend of ortho-carborane > meta-carborane > para-carborane > C6F5 > C6H5.

Bis(1-Methyl-ortho-Carboranyl)Borane.

The Lewis superacid, bis(1-methyl-ortho-carboranyl)borane, is rapidly accessed in two steps. It is a very effective hydroboration reagent capable of B-H addition to alkenes, alkynes, and cyclopropanes. To date, this is the first identified Lewis superacidic secondary borane and most reactive neutral hydroboration reagent.

Accessing Boron-Doped Pentaphene Analogues from 12-Boradibenzofluorene.

Borole-doped polycyclic aromatic hydrocarbons (PAHs) have garnered attention in recent years due to their attractive photophysical properties and potential utility in electronic devices. In this work, a borole-doped PAH, 12-boradibenzofluorene, is synthesized and formal intermolecular nitrene and oxygen atom insertion reactions were employed to access 1,2-azaborine- and 1,2-oxaborine-containing analogues of the carbonaceous PAH pentaphene. Iodosobenzene is established as a versatile reagent for oxygen atom insertion reactions into a variety of borole species to access 1,2-oxaborine systems.

On the potential intermediacy of PhIBr2 as a brominating agent.

PhIBr2, first purported to exist over 100 years ago, has been subject of few reports due to its low stability. However, a recent publication proposes a reaction of PIFA (PhI(OC(O)-CF3)2) with TMSBr to form PhIBr2in situ and demonstrated its efficacy in aryl brominations. This report investigates this synthesis by replicating bromination reactions claiming to use in situ PhIBr2 as described. The spectroscopical and computational results indicate formation of PhI and Br2 where Br2 is responsible for bromination and no supporting evidence for invoking PhIBr2 as an intermediate is found.

Synthesis and Structural Verification of an ArI(OTf)2 , NO2 -Ph-I(OTf)2.

PhI(OTf)2 and related ArI(OTf)2 species have been incorrectly invoked as intermediates in oxidation reactions for many years. We recently established that such compounds did not yet exist but remain an attractive target. Here we describe the synthesis, isolation, and structural characterization of NO2 -PhI(OTf)2, which is resistant to decomposition and more reactive than PhI(OTf)(OAc), the species previously misidentified as PhI(OTf)2 .

Tris(ortho-carboranyl)borane: An Isolable, Halogen-Free, Lewis Superacid.

The synthesis of tris(ortho-carboranyl)borane (BoCb3 ), a single site neutral Lewis superacid, in one pot from commercially available materials is achieved. The high fluoride ion affinity (FIA) confirms its classification as a Lewis superacid and the Gutmann-Beckett method as well as adducts with Lewis bases indicate stronger Lewis acidity over the widely used fluorinated aryl boranes. The electron withdrawing effect of ortho-carborane and lack of pi-delocalization of the LUMO rationalize the unusually high Lewis acidity. Catalytic studies indicate that BoCb3 is a superior catalyst for promoting C-F bond functionalization reactions than tris(pentafluorophenyl)borane [B(C6 F5 )3 ].

Ligation of Boratabenzene and 9-Borataphenanthrene to Coinage Metals.

The reactions of boratabenzene and borataphenanthrene anions with group 11 Ph3PMCl reagents furnished η2 coordination complexes, with the exception of the copper boratabenzene species that adopted an η6 mode. The binding of arene ligands to copper in an η6 manner is rare, and altering the ancillary ligand on copper to an N-heterocyclic carbene switched the binding of the boratabenzene to η2, indicating that such ligands are capable of vacating coordination sites. The η2 coordination complexes bind side-on, akin to olefins, via a borataalkene unit, although with the carbon atom much more proximal to the metal center than boron.

PhI(OTf)2 Does Not Exist (Yet)*.

PhI(OTf)2 has been used for the past 30 years as a strong I(III) oxidant for organic and inorganic transformations. It has been reported to be generated in situ from the reactions of either PhI(OAc)2 or PhI=O with two equivalents of trimethylsilyl trifluoromethanesulfonate (TMS-OTf). In this report it is shown that neither of these reactions generate a solution with spectroscopic data consistent with PhI(OTf)2 , with supporting theoretical calculations, and thus this compound should not be invoked as the species acting as the oxidant for transformations that have been associated with its use.

Metathesis Reactions between Heavy d-8 Fluorides and I(III)-Pyridine Complexes.

The reaction between trans-[AuF2(pyridine)2]+ and [PhI(pyridine)2]2+ results in the formation of PhIF2 and [Au(pyridine)4]3+. Investigation of the reaction pathway using model Pd and Pt analogues of the gold complex indicate that the most likely mechanism is attack by the Au-F onto the I(III), rather than a redox process. This demonstrates that the Au(III)-F fragment can behave in a nucleophilic manner even in a relatively electron-poor cationic complex.

The 9-Borataphenanthrene Anion.

The 9-borataphenanthrene anion is easily accessed by deprotonation of a 9,10-dihydro-9-boraphenanthrene and its diverse reactivity is investigated. Alkylation occurs at the carbon atom adjacent to boron, and room temperature hydroboration occurs across the B=C bond. The π-manifold of the central BC5 ring coordinates to chromium in an η6 fashion while only the B=C unit binds η2 to gold, indicating versatility of the 9-borataphenanthrene anion as a ligand. Supporting calculations rationalize the reactivity and aromaticity is corroborated by nucleus-independent chemical shift (NICS) indices.

Diverse Reactivity of Dienes with Pentaphenylborole and 1-Phenyl-2,3,4,5-Tetramethylborole Dimer.

The reactions of a monomeric borole and a dimeric borole with 2,3-dimethyl-1,3-butadiene and 1,3-cyclohexadiene were investigated. The monomeric borole reacted at ambient temperature whereas heat was required to crack the dimer to form the monomer and induce reactivity. 2,3-Dimethyl-1,3-butadiene reacts to give diverse products resulting from a cycloaddition process with the B-C moiety of the boroles acting as a dienophile, followed by rearrangements to furnish bicyclic species. For 1,3-cyclohexadiene, a [4+2] process is observed in which 1,3-cyclohexadiene serves as the dienophile and the boroles as the diene partner. The experimental results are corroborated with mechanistic theoretical calculations that indicate boroles can serve as either a diene or dienophile in cycloaddition reactions with dienes.

Revisiting the Perfluorinated Trityl Cation.

Although ultimately not isolable for X-ray structural characterization, the free perfluorinated trityl cation was shown to be observable in neat triflic acid, which represents milder conditions than previous reports of this cation in "magic acid" or oleum. A triflate-bound species could be generated in organic solvents using stoichiometric amounts of triflic acid and was shown to be synthetically viable for hydride abstraction from Et3 SiH. It was demonstrated that the para-position on the -C6 F5 rings is the primary point of attack for decomposition of the cation.

Evaluation of the σ-Donating and π-Accepting Properties of N-Heterocyclic Boryl Anions.

The relative σ-donating and π-accepting capacities of a range of synthetically relevant boryl anions have been evaluated by examining the geometric, thermochemical, and electronic properties of their adducts to the Li+ cation and Se atom, as compared to the properties of the analogous neutral N-heterocyclic carbenes (NHCs), by theoretical methods. The results indicate that boryl anions have a weaker π-accepting capability compared to NHCs, but it is still a non-negligible factor in the bonding contributions between boryl and the Se atom. The tunability of the π-accepting capacity of boryl anions is similar to that of NHCs, indicating a potential for the modification of the electronic properties of metal complexes incorporating either boryl or NHC ligands. In all cases, the boryl ligands were found to be superior σ-donors to NHCs.

Cyclic(alkyl)(amino) Carbene-Promoted Ring Expansion of a Carbodicarbene Beryllacycle.

Recent synthetic efforts have uncovered several bond activation pathways mediated by beryllium. Having the highest charge density and electronegativity, the chemistry of beryllium often diverges from that of its heavier alkaline earth metal congeners. Herein, we report the synthesis of a new carbodicarbene beryllacycle (2). Compound 2 converts to 3 via an unprecedented cyclic(alkyl)(amino) carbene (CAAC)-promoted ring expansion reaction (RER). While CAAC activates a carbon-beryllium bond, N-heterocyclic carbene (NHC) coordinates to beryllium to give the tetracoordinate complex 4, which contains the longest carbeneC-Be bond to date at 1.856(4) Å. All of the compounds were fully characterized by X-ray crystallography, Fourier transform infrared spectroscopy, and 1H, 13C, and 9Be NMR spectroscopy. The ring expansion mechanism was modeled with both NHC and CAAC using density functional theory calculations. While the activation energy for the observed beryllium ring expansion with CAAC was found to be 14 kJ mol-1, the energy barrier for the hypothetical NHC RER is significantly higher (199.1 kJ mol-1).

Exploiting Pincer Ligands to Perturb the Geometry at Boron.

Boranes are ubiquitous in synthesis and materials but advancements in their development have been primarily restricted to the geometric energetic minima, trigonal planar complexes. This report discloses a class of boranes with expanded bond angles achieved by taking advantage of the structural rigidity of tridentate pincer ligands. The bonding of these novel boranes is investigated by X-ray crystallography and computationally.

NHC-Stabilised Acetylene-How Far Can the Analogy Be Pushed?

Experimental studies suggest that the compound (NHCbz )2 C2 H2 can be considered as a complex of a distorted acetylene fragment which is stabilised by benzoannelated N-heterocyclic carbene ligands (NHCbz )→(C2 H2 )←(NHCbz ). A quantum chemical analysis of the electronic structures shows that the description with dative bonds is more favourable than with electron-sharing double bonds (NHCbz )=(C2 H2 )=(NHCbz ).

Diverse Reactions of Thiophenes, Selenophenes, and Tellurophenes with Strongly Oxidizing I(III) PhI(L)2 Reagents.

We report the outcomes of the reactions of aromatic group 16 thiophene, selenophene, and tellurophene rings with the I(III) oxidants PhI(OAc)(OTf) and [PhI(Pyr)2][OTf]2 (Pyr = pyridine). In all reactions, oxidative processes take place, with generation of PhI as the reduction product. However, with the exception of tellurophene with PhI(OAc)(OTf), +4 oxidation state complexes are not observed, but rather a variety of other processes occur. In general, where a C-H unit is available on the 5-membered ring, an electrophilic aromatic substitution reaction of either -IPh or pyridine onto the ring occurs. When all positions are blocked, reactions with PhI(OAc)(OTf) give acetic and triflic anhydride as the identifiable oxidative byproducts, while [PhI(Pyr)2][OTf]2 gives pyridine electrophilic aromatic substitution onto the peripheral rings. Qualitative mechanistic studies indicate that the presence of the oxidizable heteroatom is required for pyridine to act as an electrophile in a substantial manner.

A Strong cis-Effect in an Imidazole-Imidazolium-Substituted Alkene.

We report the first example of an alkene with two carbon-bound substituents (imidazole and imidazolium rings) where the Z-isomer has a greater thermodynamic stability than the E-isomer which persists in both the gas phase and in solution. Theoretical calculations, solution fluorescence spectroscopy and gas-phase ion mobility mass spectrometry studies confirm the preference for the Z-isomer, the stability of which is traced to a non-covalent interaction between the imidazole lone pair and the imidazolium ring.