Fluorination/Dearomatization of C6F5 Groups: An FLP Route to an Electrophilic Borane and Non-Coordinating Anions.

B(C6F5)3 and the corresponding anion [B(C6F5)4]- are ubiquitous in main group and transition metal chemistry. Known derivatives are generally limited to the incorporation of electron donating substituents. Herein we describe electrophilic fluorination and dearomatization of such species using XeF2 in the presence of BF3 or Lewis acidic cations. In this fashion the anions [HB(C6F5)3]-, [B(C6F5)4]- and [(C6F5)3BC≡NB(C6F5)3]-, are converted to [FB(C6F7)3]-, [B(C6F7)4]-, and [(C6F7)3BC≡NB(C6F7)3]-, respectively. Similarly, the borane adducts (L)B(C6F7)3 (L=MeCN, OPEt3) are produced. These rare examples of electrophilic attack of electron deficient rings proceed as [XeF][BF4] acts as a frustrated Lewis pair effecting fluorination and dearomatization of C6F5 rings.

Reversible Postsynthetic Modification in a Metal-Organic Framework.

Postsynthetic modification (PSM) of metal-organic frameworks (MOFs) provides access to functional materials and advanced porous solid engineering. Herein, we report the reversible PSM of a multivariate isoreticular MOF by applying dynamic furan-maleimide Diels-Alder (DA) chemistry. The key step involves incorporating a furan group into the MOF via "click" PSM, which can then undergo repeated cycles of modification and de-modification with maleimides. The structural integrity, crystallinity, and porosity of the furan-appended MOF remained intact even after three consecutive PSM/de-modification cycles using three different functionalized maleimides.

A Facile and High-Sensitivity Method for Determining Proteinogenic Amino Acid Enantiomers by Integrating Chiral Phosphinate Derivatizing, 31P NMR and Parallel Reaction Monitoring.

Here, we have documented a new protocol to determine d/l-amino acids by derivatizing amino acids via a chiral phosphinate. (RP)-l-Menthyl phenylphosphinate was able to bond both primary and secondary amines, as well as improve the sensitivity of analytes in MS. Eighteen pairs of amino acids were successfully labeled except for Cys which has a thiol group on the side chain, and the chirality of amino acids can be discriminated by 31P NMR. Seventeen pairs of amino acids were separated by a C18 column within 45 min of elution, and resolution values ranged from 2.01 to 10.76. The lowest limit of detection was 10 pM acquired at parallel reaction monitoring, in which two factors collectively contributed that the ability of protonation of phosphine oxide and the sensitivity of parallel reaction monitoring. Chiral phosphine oxides might be a promising tool in future chiral metabolomics.

Reactions of Diethylazo-Dicarboxylate with Frustrated Lewis Pairs.

Reactions of PAr3 /B(C6 F5 )3 (Ar=o-Tol, Mes, Ph) FLPs with diethyl azodicarboxylate (DEAD) afford the corresponding FLP addition products 1-3 in which P-N and B-O linkages are formed. In contrast, the reaction of BPh3 , PPh3 and DEAD gave product 4 where P-N and N-B linkages were confirmed. In all cases, other binding modes were computed to be both higher in energy and readily distinguishable by 31 P and 11 B NMR parameters. These data illustrate the influence of steric demands and electronic structures on the nature of the products of FLP reactions with DEAD.

Reactions of Frustrated Lewis Pairs with Chloro-Diazirines: Cleavage of N=N Double Bonds.

The reactions of FLPs with diazomethanes leads to the rapid loss of N2 . In contrast, in this work, we reported reactions of phosphine/borane FLPs with chlorodiazirines which led to the reduction of the N=N double bond, affording linked phosphinimide/amidoborate zwitterions of the general form R3 PNC(Ar)NR'BX(C6 F5 )2 . A detailed DFT mechanistic study showed that these reactions proceed via FLP addition to the N=N bond, followed by subsequent group transfer reactions to nitrogen and capture of the halide anion.

Fluorine-18 Labeling of Difluoromethyl and Trifluoromethyl Groups via Monoselective C-F Bond Activation.

We report a general method for the labeling of both CF3 and CF2 H groups in a broad range of chemical settings (aryl, oxide, sulfide). The method utilizes frustrated Lewis pair mediated selective C-F activation to formally substitute fluorine-19 with fluorine-18 in a two-step defluorination/radiofluorination process, and as such can utilize the target compounds as starting materials. The radiotracer precursors can be isolated as stable salts prior to radiofluorination. The method delivers good radiochemical yields and molar activities (up to 35.2±6.5 % non-decay corrected isolated activity yields and 12.0±1.7 GBq µmol-1 molar activities) and is shown to be applicable to biologically relevant compounds. The ability to utilize the target compound as the starting material and the synthetic simplicity of the method coupled with the ever-increasing use of CF3 and CF2 H groups in pharmaceuticals makes this method attractive for drug and radiotracer development.

Frustrated Lewis-Pair-Meditated Selective Single Fluoride Substitution in Trifluoromethyl Groups.

Single fluoride substitution in trifluoromethylarenes is an ongoing synthetic challenge that often leads to "over-reaction", where multiple fluorides are replaced. Development of this reaction would allow simple access to a vast range of difluoromethyl derivatives of current interest to pharmaceutical, agrochemistry, and materials sciences. Using a catalytic frustrated Lewis pair approach, we have developed a generic protocol that allows a single substitution of one fluoride in trifluoromethyl groups with neutral phosphine and pyridine bases. The resulting phosphonium and pyridinium salts can be further functionalized via nucleophilic substitution, photoredox coupling, and electrophilic transfer reactions allowing the generation of a vast array of difluoromethyl products.

Selective Monodefluorination and Wittig Functionalization of gem-Difluoromethyl Groups to Generate Monofluoroalkenes.

Monodefluorination of gem-difluoromethyl groups is achieved using a frustrated Lewis pair (FLP) approach. Triarylphosphines and group 13 Lewis acids were surveyed as FLP components, with the combination of P( o-Tol)3 and B(C6F5)3 found to provide the best results, although the reaction is feasible with more economical components (PPh3 and BF3·OEt2). The α-fluoroalkylphosphonium products arising from the reaction were of lower activity, in regard to further fluoride abstraction, as compared to difluoride starting materials, leading to highly selective monodefluorination. The activated substrates were subject to Wittig reaction protocols to generate a variety of monofluoroalkenes in moderate to high yields.

Multi-stimuli-responsive organometallic gels based on ferrocene-linked poly(aryl ether) dendrons: reversible redox switching and Pb2+-ion sensing.

We describe the design, synthesis, and "stimuli-responsive" study of ferrocene-linked Fréchet-type [poly(aryl ether)]-dendron-based organometallic gels, in which the ferrocene moiety is attached to the dendron framework through an acyl hydrazone linkage. The low-molecular-weight gelators (LMWGs) form robust gels in both polar and non-polar solvent/solvent mixtures. The organometallic gels undergo stimuli-responsive behavior through 1) thermal, 2) chemical, and 3) electrochemical methods. Among them, conditions 1 and 3 lead to seamlessly reversible with repeated cycles of identical efficiency. Results indicate that the flexible nature of the poly(aryl ether) dendron framework plays a key role in retaining the reversible electrochemical behavior of ferrocene moiety in the LMWGs. Further, the organometallic gelators have exhibited unique selectivity towards Pb(2+) ions (detection limit ≈10(-8) M). The metal ion-sensing results in a gel-sol phase transition associated with a color change visible to the naked eye. Most importantly, decomplexing the metal ion from the system leads to the regeneration of the initial gel morphology, indicating the restoring ability of the organometallic gel. The metal-ligand binding nature has been analyzed by using (1)H NMR spectroscopy, mass spectrometry, and DFT calculations.

The impact of Lewis acid variation on reactions with di-tert-butyl diazo diesters.

Reactions of (tBuO2CN)2 with Lewis acids and FLPs have previously been shown to prompt the formation of diazene compounds. In this work, we show that the reaction of (tBuO2CN)2 with 9-BBN leads to a bicyclic heterocyclic product (tBuOCO(BBN)CN)21. In contrast, the reactions of (tBuO2CN)2 with BF3 or [Et3Si][B(C6F5)4] lead to the isolation of [tBuNHNH2tBu][BF4] 2 and [tBuN(H)NtBu][B(C6F5)4] 3, respectively. The mechanism for the formation of 2 is probed computationally, demonstrating that steric and electronic considerations of the Lewis acid impact the reaction pathway.

Sensitive and selective redox, chromogenic, and "turn-on" fluorescent probe for Pb(II) in aqueous environment.

The electrochemical, optical, and metal cation sensing properties of the triazole-tethered ferrocene-anthracene conjugates, C(48)H(40)FeO(2)N(6) (3) and C(52)H(40)FeO(2)N(6) (4), and the ferrocene-pyrene conjugates, C(29)H(25)FeON(3) (5) and C(31)H(25)FeON(3) (6), have been documented. All the compounds 3-6 behave as very selective redox, chromogenic, and "turn-on" fluorescent probes for Pb(2+) ion in an aqueous environment (CH(3)CN/H(2)O, 2/8). The significant changes in their absorption spectra are accompanied by a strong color change from yellow to greenish blue, which allows a prospective use for the "naked eye" detection of Pb(2+) ion over other competitor cations such as Hg(2+) and Cd(2+). These chemosensors present immense brightness and fluorescence enhancement (chelation-enhanced fluorescence = 85 for 3 and 92 for 4) following Pb(2+) coordination within the limit of detection at 2 ppb. Interestingly, their fluorescence, redox, and colorimetric responses are preserved in presence of water, which can be used for the selective colorimetric detection of Pb(2+) ion in aqueous environment over Hg(2+) and Cd(2+) cations. All the compounds have been characterized by (1)H, (13)C NMR spectroscopy and electrospray ionization mass spectrometry (ESI-MS) spectrometric analysis, and the solid-state structures of 5 and 6 have been unequivocally established by X-ray diffraction analysis.

Electron-deficient cyclopropenium cations as Lewis acids in FLP chemistry.

Cyclopropenium cations incorporating electron deficient substituents are Lewis acidic despite the presence of π-electrons. The chloride and electron affinities are examined computationally and experimentally, respectively. These cations form classic Lewis acid-base adducts with PPh3, while sterically demanding phosphines yield frustrated Lewis pairs (FLPs) which participate in FLP additions. Depending on the basicity of the phosphine used, addition to alkynes or alkyne deprotonation is observed. In either case, new C-C bonds are formed, thus extending the utility of the concept of FLP chemistry to these delocalized π-cations.

Transient hydroboration and hydroalumination of activated azo-species: avenues to NBO and NAlO-heterobicycles.

Reactions of the boranes, BH(C6F5)2 or 9-BBN, with azodicarboxylates or an azodicarbonylamide provide facile access to NBO heterocyclic compounds. The products [(C6F5)2BOC(X)N]2 X = OEt 1, OiPr 2, OCH2CCl33, OCH2Ph 4, NC5H105) and [(9-BBN)OC(X)N]2 (X = OEt 6, OiPr 7, NC5H108) and [Ph2B)OC(OtBu)N]29 were prepared. In another variation, (nacnac)AlH2 (nacnac = (C6H3iPr2NC(Me))2CH) afforded the Al-heterobicycle [(nacnac)Al(H)OC(OEt)N]210. The mechanism for the formation of these products is proposed to involve transient hydroboration or hydroalumination of the NN double bond.

B(C6F5)3-Catalyzed site-selective N1-alkylation of benzotriazoles with diazoalkanes.

Alkylation of benzotriazoles is synthetically challenging, often leading to mixtures of N1 and N2 alkylation. Herein, metal-free catalytic site-selective N1-alkylation of benzotriazoles with diazoalkanes is described in the presence of 10 mol% of B(C6F5)3. These reactions provide N1-alkylated benzotriazoles in good to excellent yields and this protocol is successfully adapted to gram-scale syntheses as well as a derivative with antimicrobial activity.

FLP-Catalyzed Monoselective C-F Functionalization in Polyfluorocarbons at Geminal or Distal Sites.

We report frustrated Lewis pair (FLP)-catalyzed monoselective C-F activation in a range of aliphatic polyfluorocarbons with equivalent geminal and distal C-F positions. This methodology can be applied to aromatic-, ether-, thioether-, and alkyl-supported fluoromethyl groups. We expand the range of FLP base partners that work with monoselective C-F activation to include sulfide. The activated products can be subsequently functionalized via SN2 substitutions, photoredox-alkylations, and Suzuki couplings.

Double deboronation and homometalation of 1,1'-bis(ortho-carborane).

Double deboronation of 1,1'-bis(ortho-carborane) results in a mixture of racemic and meso diastereoisomers which are sources of the [7-(7'-7',8'-nido-C2B9H10)-7,8-nido-C2B9H10]4- tetraanion. Consistent with this, metalation of the mixture with {Ru(p-cymene)} affords the diastereoisomers α-[1-(8'-2'-(p-cymene)-2',1',8'-closo-RuC2B9H10)-3-(p-cymene)-3,1,2-closo-RuC2B9H10] (3α) and ß-[1-(8'-2'-(p-cymene)-2',1',8'-closo-RuC2B9H10)-3-(p-cymene)-3,1,2-closo-RuC2B9H10] (3ß) in which the primed cage has undergone a spontaneous 3',1',2' to 2',1',8'-RuC2B9 isomerisation. Analogous cobaltacarboranes α-[1-(8'-2'-Cp-2',1',8'-closo-CoC2B9H10)-3-Cp-3,1,2-closo-CoC2B9H10] (4α) and ß-[1-(8'-2'-Cp-2',1',8'-closo-CoC2B9H10)-3-Cp-3,1,2-closo-CoC2B9H10] (4ß) are formed by metalation with CoCl2/NaCp followed by oxidation, along with a small amount of the unique species [8-(8'-2'-Cp-2',1',8'-closo-CoC2B9H10)-2-Cp-2,1,8-closo-CoC2B9H10] (5) if the source of the tetraanion is [HNMe3]2[7-(7'-7',8'-nido-C2B9H11)-7,8-nido-C2B9H11]. Two-electron reduction and subsequent reoxidation of 4α and 4ß afford species indistinguishable from 5. The reaction between [Tl]2[1-(1'-3',1',2'-closo-TlC2B9H10)-3,1,2-closo-TlC2B9H10] and [CoCpI2(CO)] leads to the isolation of a further isomer of (CpCoC2B9H11)2, rac-[1-(1'-3'-Cp-3',1',2'-closo-CoC2B9H10)-3-Cp-3,1,2-closo-CoC2B9H10] (6), which displays intramolecular dihydrogen bonding. Thermolysis of 6 yields 4α, allowing a link to be established between the α and ß forms of 3 and 4 and racemic and meso forms of the [7-(7'-7',8'-nido-C2B9H10)-7,8-nido-C2B9H10]4- tetraanion, whilst reduction-oxidation of 6 again results in a product indistinguishable from 5.

Steric versus electronic factors in metallacarborane isomerisation: nickelacarboranes with 3,1,2-, 4,1,2- and 2,1,8-NiC2B9 architectures and pendant carborane groups, derived from 1,1'-bis(o-carborane).

Metalation of the [7-(1'-1',2'-closo-C2B10H11)-7,8-nido-C2B9H10](2-) dianion with various {NiPP(2+)} or {NiP2(2+)} fragments (PP = chelating diphosphine; P = monodentate phosphine or phosphite) leads either to unisomerised 3,1,2-NiC2B9 species or to isomerised 4,1,2-NiC2B9 or 2,1,8-NiC2B9 species, all with a pendant C2B10 substituent. The products [1-(1'-1',2'-closo-C2B10H11)-3-dppe-3,1,2-closo-NiC2B9H10] (1), [2-(1'-1',2'-closo-C2B10H11)-4-dppe-4,1,2-closo-NiC2B9H10] (2), [8-(1'-1',2'-closo-C2B10H11)-2-dmpe-2,1,8-closo-NiC2B9H10] (3), [1-(1'-1',2'-closo-C2B10H11)-3,3-(PMe3)2-3,1,2-closo-NiC2B9H10] (4), [1-(1'-1',2'-closo-C2B10H11)-3,3-(PMe2Ph)2-3,1,2-closo-NiC2B9H10] (6), [1-(1'-1',2'-closo-C2B10H11)-3,3-{P(OMe)3}2-3,1,2-closo-NiC2B9H10] (9) and [1-(1'-1',2'-closo-C2B10H11)-2,2-{P(OMe)3}2-2,1,8-closo-NiC2B9H10] (10) were fully characterised spectroscopically and crystallographically, whilst [2-(1'-1',2'-closo-C2B10H11)-4,4-(PMePh2)2-4,1,2-closo-NiC2B9H10] (8) was characterised spectroscopically. Overall the results suggest that an important factor in a 3,1,2 to 4,1,2 isomerisation is the relief gained from steric crowding, whereas a 3,1,2 to 2,1,8 isomerisation appears to be favoured by strongly electron-donating ligands on the metal.

Synthesis and crystal structures of the racemic and meso forms of [1-{1'-4'-cyclopentadienyl-4'-cobalta-1',12'-dicarba-closo-dodecaboranyl(10)}-4-cyclopentadienyl-4-cobalta-1,12-dicarba-closo-dodecaborane(10)], the former as its tetrahydrofuran disolvate.

Both rac-[1-(1'-4'-Cp-4',1',12'-closo-CoC2B10H11)-4-Cp-4,1,12-closo-CoC2B10H11]·2THF (Cp is cyclopentadienyl and THF is tetrahydrofuran) or [Co2(C5H5)2(C4H22B20)]·2C4H8O, (1), and meso-[1-(1'-4'-Cp-4',1',12'-closo-CoC2B10H11)-4-Cp-4,1,12-closo-CoC2B10H11] or [Co2(C5H5)2(C4H22B20)], (2), were prepared by thermolysis of a rac/meso mixture of the precursor species [1-(1'-4'-Cp-4',1',6'-closo-CoC2B10H11)-4-Cp-4,1,6-closo-CoC2B10H11] and were separated, spectroscopically characterized and studied crystallographically. Cage C-atom identification was accomplished by both the vertex-to-centroid distance and boron-hydrogen distance methods, and, in both cases, the structure established crystallographically is fully consistent with the spectroscopic data. Both the rac-(1) and meso-(2) forms share the same overall conformation (Co-C-C'-Co' ca 136°) and show clear evidence of intramolecular steric crowding resulting in tilted cyclopentadienyl ligands.