Synergic deprotonation generates alkali-metal salts of tethered fluorenide NHC ligands co-complexed to alkali metal amides

Synergic combinations of alkali-metal hydrocarbyl/amide reagents were used to synthesise saturated N-heterocyclic carbene (NHC) ligands tethered to a fluorenide anion through deprotonation of a spirocyclic precursor, whereas conventional bases were not successful. The Li2 derivatives displayed a bridging amide between two Li atoms within the fluorenide-NHC pocket, whereas the Na2 and K2 analogues displayed extended solid-state structures with the fluorenide-NHC ligand chelating one alkali metal centre

Indenyl rhodium N-Heterocyclic carbene complexes for catalytic C-H borylation

Metal-catalysed C-H activation offers the ability to access key synthetic targets in more straightforward reactions than previously used methods. However, undirected activation pathways face issues of selectivity and low rates of reaction that make substituting simple hydrocarbons difficult. Indenyl (Ind) and fluorenyl ligands offer increased reactivity compared to cyclopentadienyl groups, which have been used previously in C-H borylation, and combining these donors with electron-donating NHC ligands was investigated for the borylation of arenes and alkanes. Additionally, the effects of tethered systems were explored to see whether the catalytic ability is enhanced. [Rh(Ind)(SIPr)(C2H4)], [Rh(Ind)(SIPr)(COE)] and [Rh(Ind)(SIPr)(CO)] (SIPr = 1,3- bis(2,6-diisopropylphenyl)-4,5-dihydroimidazol-2-ylidene, COE = cis-cyclooctene) were synthesised and characterised by multinuclear NMR spectroscopy and X-ray diffraction. Only the ethylene and cyclooctene complexes were found to be reactive under photolytic conditions and towards silanes. Photolysis led to the loss of coordinated alkenes and the formation of a cyclometallated species due to C-H activation of the NHC substituents. With reducing silanes or hydrogen, a rhodium dihydride complex was observed, that is hypothesised to form via the reaction of the cyclometallated species, while less reducing silanes led to the formation of the oxidative addition product. Both [Rh(Ind)(SIPr)(C2H4)] and [Rh(Ind)(SIPr)(COE)] were found to be catalytically competent for the borylation of benzene, while the carbonyl complex was found to be unreactive under these conditions. Borylation of a selection of arenes showed that the selectivity was comparable to previously reported rhodium catalysts, which is dominated by steric effects, however, the reactivity was lower compared to previously reported catalysts such as [RhCp*(C6Me6)]. Borylation of decane and octane showed that the cyclooctene complex was capable of borylating alkanes, albeit in low yields. Stoichiometric experiments monitored by NMR spectroscopy provided evidence that the catalysis proceeds via rhodium boryl hydride species, with the previously identified cyclometallated species also likely to play a role. The synthesis of fluorenyl-tethered saturated-NHC ligands required the development of homobimetallic synergic bases in order to bring about a ring-opening deprotonation of a spirocyclic intermediate. The structure of [Li2(μ2 ‐Ph){μ2 ‐N(SiMe3)2}] was crystallographically characterised as a coordination polymer, and reaction with the spirocyclic compound led to the formation of dialkali metal complexes of a fluorenidetehered NHC ligand that incorporated a bridging amide group. The use of these bimetallic complexes as ligand transfer reagents gave rhodium carbonyl and ethene complexes in low yields. Initial testing of these complexes in the borylation of benzene found that the carbonyl species was inactive while the ethene complex was less active than the related monodentate species. Overall, this research has demonstrated that NHC ligands can be used to develop Rhcomplexes capable of C-H activation, the oxidative addition of silanes and the catalytic borylation of hydrocarbons. This supports the idea that a [Rh(Ind)(NHC)] fragment (16 electron for η 5 -indenyl, or 14 electron with η 3 -indenyl) can mimic the reactivity of the previously successful [Rh(Cp)(L)] and [Rh(Cp*)] fragments. Although the compounds synthesised in this thesis were not better catalysts than literature examples, they hold much promise because the incorporation of a tuneable NHC ligand on the metal centre can lead to future improvements, especially considering the potential importance of cyclometallated species in C-H activation reactivit

An indenide-tethered N-heterocyclic stannylene

The structure of (μ-1κN:2(η2),κ2N,N′-(2-{[2,6-bis(propan-2-yl)phen­yl]aza­nid­yl}eth­yl)[2-(1H-inden-1-yl)eth­yl]aza­nido)(1,4,7,10,13,16-hexa­oxa­cyclo­octa­dec­ane-1κ6O)lithiumtin, [LiSn(C8H16O4)(C25H31N2)], at 100 K has monoclinic (P21/n) symmetry. Analysis of the coordination of the Sn to the indenyl ring shows that the Sn inter­acts in an η2 fashion. A database survey showed that whilst this coordination mode is unusual for Ge and Pb compounds, Sn displays a wider range of coordination modes to cyclo­penta­dienyl ligands and their derivatives

Rhodium Indenyl NHC and Fluorenyl-Tethered NHC Half-Sandwich Complexes : Synthesis, Structures and Applications in the Catalytic C−H Borylation of Arenes and Alkanes

Indenyl (Ind) rhodium N-heterocyclic carbene (NHC) complexes [Rh(η5-Ind)(NHC)(L)] were synthesised for 1,3-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazol-2-ylidene (SIPr) with L=C2H4 (1), CO (2 a) and cyclooctene (COE; 3), for 1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene (SIMes) with L=CO (2 b) and COE (4), and 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene (IMes) with L=CO (2 c) and COE (5). Reaction of SIPr with [Rh(Cp*)(C2H4)2] did not give the desired SIPr complex, thus demonstrating the “indenyl effect” in the synthesis of 1. Oxidative addition of HSi(OEt)3 to 3 proceeded under mild conditions to give the Rh silyl hydride complex [Rh(Ind){Si(OEt)3}(H)(SIPr)] (6) with loss of COE. Tethered-fluorenyl NHC rhodium complexes [Rh{(η5-C13H8)C2H4N(C)C2HxNR}(L)] (x=4, R=Dipp, L=C2H4: 11; L=COE: 12; L=CO: 13; R=Mes, L=COE: 14; L=CO: 15; x=2, R=Me, L=COE: 16; L=CO: 17) were synthesised in low yields (5–31 %) in comparison to good yields for the monodentate complexes (49–79 %). Compounds 3 and 1, which contain labile alkene ligands, were successful catalysts for the catalytic borylation of benzene with B2pin2 (Bpin=pinacolboronate, 97 and 93 % PhBpin respectively with 5 mol % catalyst, 24 h, 80 °C), with SIPr giving a more active catalyst than SIMes or IMes. Fluorenyl-tethered NHC complexes were much less active as borylation catalysts, and the carbonyl complexes were inactive. The borylation of toluene, biphenyl, anisole and diphenyl ether proceeded to give meta substitutions as the major product, with smaller amounts of para substitution and almost no ortho product. The borylation of octane and decane with B2pin2 at 120 and 140 °C, respectively, was monitored by 11B NMR spectroscopy, which showed high conversions into octyl and decylBpin over 4–7 days, thus demonstrating catalysed sp3 C−H borylation with new piano stool rhodium indenyl complexes. Irradiation of the monodentate complexes with 400 or 420 nm light confirmed the ready dissociation of C2H4 and COE ligands, whereas CO complexes were inert. Evidence for C−H bond activation in the alkyl groups of the NHC ligands was obtained

Circulating unmethylated CHTOP and INS DNA fragments provide evidence of possible islet cell death in youth with obesity and diabetes

Background Identification of islet β cell death prior to the onset of type 1 diabetes (T1D) or type 2 diabetes (T2D) might allow for interventions to protect β cells and reduce diabetes risk. Circulating unmethylated DNA fragments arising from the human INS gene have been proposed as biomarkers of β cell death, but this gene alone may not be sufficiently specific to report β cell death. Results To identify new candidate genes whose CpG sites may show greater specificity for β cells, we performed unbiased DNA methylation analysis using the Infinium HumanMethylation 450 array on 64 human islet preparations and 27 non-islet human tissues. For verification of array results, bisulfite DNA sequencing of human β cells and 11 non-β cell tissues was performed on 5 of the top 10 CpG sites that were found to be differentially methylated. We identified the CHTOP gene as a candidate whose CpGs show a greater frequency of unmethylation in human islets. A digital PCR strategy was used to determine the methylation pattern of CHTOP and INS CpG sites in primary human tissues. Although both INS and CHTOP contained unmethylated CpG sites in non-islet tissues, they occurred in a non-overlapping pattern. Based on Naïve Bayes classifier analysis, the two genes together report 100% specificity for islet damage. Digital PCR was then performed on cell-free DNA from serum from human subjects. Compared to healthy controls (N = 10), differentially methylated CHTOP and INS levels were higher in youth with new onset T1D (N = 43) and, unexpectedly, in healthy autoantibody-negative youth who have first-degree relatives with T1D (N = 23). When tested in lean (N = 32) and obese (N = 118) youth, increased levels of unmethylated INS and CHTOP were observed in obese individuals. Conclusion Our data suggest that concurrent measurement of circulating unmethylated INS and CHTOP has the potential to detect islet death in youth at risk for both T1D and T2D. Our data also support the use of multiple parameters to increase the confidence of detecting islet damage in individuals at risk for developing diabetes

Frontispiece:functionalised N-heterocyclic carbene ligands in bimetallic architectures

N-Heterocyclic carbenes (NHCs) have become immensely successful ligands in coordination chemistry and homogeneous catalysis due to their strong terminal σ-donor properties. However, by targeting NHC ligands with additional functionalisation, a new area of NHC coordination chemistry has developed that has enabled NHCs to be used to construct bimetallic and multimetallic architectures. In their Minireview on page 5927 ff., S. M. Mansell and K. J. Evans discuss the development of functionalised NHC ligands that incorporate additional donor sites in order to coordinate two or more metal atoms. This can be through the N-atom of the NHC ring, through a donor group attached to the N-atom or the carbon backbone, coordination of the π-bond or an annulated π-donor on the backbone, or through direct metalation of the backbone

Frontispiece: Functionalised N‐Heterocyclic Carbene Ligands in Bimetallic Architectures

N-Heterocyclic carbenes (NHCs) have become immensely successful ligands in coordination chemistry and homogeneous catalysis due to their strong terminal σ-donor properties. However, by targeting NHC ligands with additional functionalisation, a new area of NHC coordination chemistry has developed that has enabled NHCs to be used to construct bimetallic and multimetallic architectures. In their Minireview on page 5927 ff., S. M. Mansell and K. J. Evans discuss the development of functionalised NHC ligands that incorporate additional donor sites in order to coordinate two or more metal atoms. This can be through the N-atom of the NHC ring, through a donor group attached to the N-atom or the carbon backbone, coordination of the π-bond or an annulated π-donor on the backbone, or through direct metalation of the backbone

On the Reactivity of N-tert-Butyl-1,2-Diaminoethane: Synthesis of 1-tert-Butyl-2-Imidazoline, Formation of an Intramolecular Carbamate Salt from the Reaction with CO2, and Generation of a Hydroxyalkyl-Substituted Imidazolinium Salt

N-tert-Butyl-1,2-diaminoethane was shown to react rapidly with atmospheric carbon dioxide to generate the zwitterionic ammonium carbamate salt CO2N(H)C2H4N(H)2tBu (1). Reaction of N-tert-butyl-1,2-diaminoethane with triethylorthoformate gave 1-tert-butyl-2-imidazoline (2) in 24% yield after fractional distillation, and the hydroxyalkyl-tethered imidazolinium salt [HOC(Me)2CH2NC2H4N(CH)tBu][Cl] (3) was synthesised from the sequential reaction of N-tert-butyl-1,2-diaminoethane with isobutylene epoxide, HCl, and triethylorthoformate

One-step synthesis of heteroleptic rare-earth amide complexes featuring fluorenyl-tethered N-heterocyclic carbene ligands

Reaction of the fluorenyl-tethered imidazolium bromide salt [9-(C13H9)C2H4N(CH)C2H2N(Me)][Br] (I) with [Y{N(SiMe3)2}3] generated the heteroleptic yttrium complex [Y{(η5-C13H8)C2H4N(κ-C)C2H2N(Me)}(Br){N(SiMe3)2}] (1), which contains an Y centre with a piano-stool geometry and four different donors. The reaction of I with [Nd{N(SiMe3)2}3] led to single crystals of the dimeric Nd complex [Nd{(η5-C13H8)C2H4N(κ-C)C2H2N(Me)}(μ-Br){N(SiMe3)2}]2 (2), likely due to the larger ionic radius of Nd3+. Reactions of I with [La{N(SiMe3)2}3], which contains the larger La3+ ion, demonstrated the formation of multiple products from ligand redistribution, including [La{(η5-C13H8)C2H4N(κ-C)C2H2N(Me)}{N(SiMe3)2}2] (3) and [La{(η5-C13H8)C2H4N(κ-C)C2H2N(Me)}2(Br)] (4)