Correction: Synthetic ramoplanin analogues are accessible by effective incorporation of arylglycines in solid-phase peptide synthesis.

[This corrects the article DOI: 10.1039/D3SC01944F.].

Lewis acid catalysed polymerisation of cyclopentenone.

A modest structural change of a ß-diketiminate-supported aluminium complex leads to dramatic differences in the reactivity towards cyclopentenone. While the bulkier complex efficiently executes Diels Alder transformations the smaller analogue performs unique polymerisation of this substrate. This observation appears to be unprecedented in the chemistry of Lewis acids and cyclic dienophiles as it represents a unique way to polymerise a functionalised olefin.

Synthetic ramoplanin analogues are accessible by effective incorporation of arylglycines in solid-phase peptide synthesis.

The threat of antimicrobial resistance to antibiotics requires a continual effort to develop alternative treatments. Arylglycines (or phenylglycines) are one of the signature amino acids found in many natural peptide antibiotics, but their propensity for epimerization in solid-phase peptide synthesis (SPPS) has prevented their use in long peptide sequences. We have now identified an optimized protocol that allows the synthesis of challenging non-ribosomal peptides including precursors of the glycopeptide antibiotics and an analogue of feglymycin (1 analogue, 20%). We have exploited this protocol to synthesize analogues of the peptide antibiotic ramoplanin using native chemical ligation/desulfurization (1 analogue, 6.5%) and head-to-tail macrocyclization in excellent yield (6 analogues, 3-9%), with these compounds extensively characterized by NMR (U-shaped structure) and antimicrobial activity assays (two clinical isolates). This method significantly reduces synthesis time (6-9 days) when compared with total syntheses (2-3 months) and enables drug discovery programs to include arylglycines in structure-activity relationship studies and drug development.

The preservation of sarin and O,O'-diisopropyl fluorophosphate inside coordination cage hosts.

The host-guest chemistry of O,O'-diisopropyl fluorophosphate (DFP), a phosphonofluoridate G-series chemical warfare agent simulant, was investigated in the presence of a number of octanuclear cubic coordination cage hosts. The aim was to demonstrate cage-catalysed hydrolysis of DFP at near neutral pH: however, two octanuclear coordination cages, HPEG (containing water-solubilising PEG groups) and HW (containing water-solubilising hydroxymethyl groups), were actually found to increase the lifetime of DFP in aqueous buffer solution (pH 8.7). Crystallographic analysis of DFP with a structurally related host cage revealed that DFP binds to windows in the cage surface, not in the internal cavity. The phosphorus-fluorine bond is directed into the cavity rather than towards the external environment, with the cage/DFP association protecting DFP from hydrolysis. Initial studies with the chemical warfare agent (CWA) sarin (GB) with HPEG cage in a buffered solution also showed a drastically reduced rate of hydrolysis for sarin when bound in the host cage. The ability of these cages to inhibit hydrolysis of these P-F bond containing organophosphorus guests, by encapsulation, may have applications in forensic sample preservation and analysis.

A photo-switchable molecular capsule: sequential photoinduced processes.

The metastable trilacunary heteropolyoxomolybdate [PMo9O31(py)3]3- - {PMo9}; py = pyridine) and the ditopic pyridyl bearing diarylethene (DAE) (C25H16N2F6S2) self-assemble via a facile ligand replacement methodology to yield the photo-active molecular capsule [(PMo9O31)2(DAE)3]6-. The spatial arrangement and conformation of the three DAE ligands are directed by the surface chemistry of the molecular metal oxide precursor with exclusive ligation of the photo-active antiparallel rotamer to the polyoxometalate (POM) while the integrity of the assembly in solution has been verified by a suite of spectroscopic techniques. Electrocyclisation of the three DAEs occurs sequentially and has been investigated using a combination of steady-state and time-resolved spectroscopies with the discovery of a photochemical cascade whereby rapid photoinduced ring closure is followed by electron transfer from the ring-closed DAE to the POM in the latent donor-acceptor system on subsequent excitation. This interpretation is also supported by computational and detailed spectroelectrochemical analysis. Ring-closing quantum yields were also determined using a custom quantum yield determination setup (QYDS), providing insight into the impact of POM coordination on these processes.

Quantitative High-Field NMR- and Mass Spectrometry-Based Fatty Acid Sequencing Reveals Internal Structure in Ru-Catalyzed Deuteration of Docosahexaenoic Acid.

Ru-based catalysis results in highly unsaturated fatty acid (HUFA) ethyl esters (EE) deuterated to various extents. The products carry 2H (D) mainly at their bis-allylic positions, where they are resistant to autoxidation compared to natural HUFA and are promising as neurological and retinal drugs. We characterized the extent of deuteration at each allylic position of docosa-4,7,10,13,16,19-hexaenoic acid deuterated to completion at bis-allylic and allylic positions (D-DHA) by two-dimensional (2D) and high-field (600 and 950 MHz) NMR. In separate experiments, the kinetics of docosahexaenoic acid (DHA) EE deuteration was evaluated using Paternò-Büchi (PB) reaction tandem mass spectrometry (MS/MS) analysis, enabling deuteration to be quantitatively characterized for isotopologues (D0-D14 DHA) at each internal allylic position. NMR analysis shows that the net deuteration of the isotopologue mixture is about 94% at the bis-allylic positions, and less than 1% remained as the protiated -CH2-. MS analysis shows that deuteration kinetics follow an increasing curve at bis-allylic positions with higher rate for internal bis-allylic positions. Percent D of bis-allylic positions increases linearly from D1 to D9 in which all internal bis-allylic positions (C9, C12, C15) deuterate uniformly and more rapidly than external bis-allylic positions (C6, C18). The mono-allylic positions near the methyl end (C21) show a steep increase of D only after the D10 isotopologue has been deuterated to >90%, while the mono-allylic position near the carboxyl position, C3, deuterates last and least. These data establish detailed methods for the characterization of Ru-catalyzed deuteration of HUFA as well as the phenomenological reaction kinetics as net product is formed.

Carbodiphosphorane-Stabilized Parent Dioxophosphorane: A Valuable Synthetic HO2P Source.

Introducing a small phosphorus-based fragment into other molecular entities via, for example, phosphorylation/phosphonylation is an important process in synthetic chemistry. One of the approaches to achieve this is by trapping and subsequently releasing extremely reactive phosphorus-based molecules such as dioxophosphoranes. In this work, electron-rich hexaphenylcarbodiphosphorane (CDP) was used to stabilize the least thermodynamically favorable isomer of HO2P to yield monomeric CDP·PHO2. The title compound was observed to be a quite versatile phosphonylating agent; that is, it showed a great ability to transfer, for the first time, the HPO2 fragment to a number of substrates such as alcohols, amines, carboxylic acids, and water. Several phosphorous-based compounds that were generated using this synthetic approach were also isolated and characterized for the first time. According to the initial computational studies, the addition-elimination pathway was significantly more favorable than the corresponding elimination-addition route for "delivering" the HO2P unit in these reactions.

A Series of Crystallographically Characterized Linear and Branched σ-Alkane Complexes of Rhodium: From Propane to 3-Methylpentane.

Using solid-state molecular organometallic (SMOM) techniques, in particular solid/gas single-crystal to single-crystal reactivity, a series of σ-alkane complexes of the general formula [Rh(Cy2PCH2CH2PCy2)(ηn:ηm-alkane)][BArF4] have been prepared (alkane = propane, 2-methylbutane, hexane, 3-methylpentane; ArF = 3,5-(CF3)2C6H3). These new complexes have been characterized using single crystal X-ray diffraction, solid-state NMR spectroscopy and DFT computational techniques and present a variety of Rh(I)···H-C binding motifs at the metal coordination site: 1,2-η2:η2 (2-methylbutane), 1,3-η2:η2 (propane), 2,4-η2:η2 (hexane), and 1,4-η1:η2 (3-methylpentane). For the linear alkanes propane and hexane, some additional Rh(I)···H-C interactions with the geminal C-H bonds are also evident. The stability of these complexes with respect to alkane loss in the solid state varies with the identity of the alkane: from propane that decomposes rapidly at 295 K to 2-methylbutane that is stable and instead undergoes an acceptorless dehydrogenation to form a bound alkene complex. In each case the alkane sits in a binding pocket defined by the {Rh(Cy2PCH2CH2PCy2)}+ fragment and the surrounding array of [BArF4]- anions. For the propane complex, a small alkane binding energy, driven in part by a lack of stabilizing short contacts with the surrounding anions, correlates with the fleeting stability of this species. 2-Methylbutane forms more short contacts within the binding pocket, and as a result the complex is considerably more stable. However, the complex of the larger 3-methylpentane ligand shows lower stability. Empirically, there therefore appears to be an optimal fit between the size and shape of the alkane and overall stability. Such observations are related to guest/host interactions in solution supramolecular chemistry and the holistic role of 1°, 2°, and 3° environments in metalloenzymes.

Using electrospray ionization-tandem mass spectrometry to explore formation and gas-phase chemistry of silver nanoclusters generated from the reaction of silver salts with NaBH4 in the presence of bis(diphenylarsino)methane.

Electrospray ionization-mass spectrometry (ESI-MS) of mixtures of AgBF4 or AgNO3 with the capping ligand bis(diphenylarsino)methane ((Ph2 As)2 CH2 = dpam) in a solution of acetonitrile revealed the formation of the following cations: [Ag(CH3 CN)(dpam)]+ , [Ag(dpam)2 ]+ , [Ag2 (Cl)(dpam)2 ]+ , and [Ag3 (Cl)2 (dpam)3 ]+ . Addition of NaBH4 to these solutions results in the formation of the cluster cations [Ag2 (BH4 )(dpam)2 ]+ , [Ag2 (BH4 )(dpam)3 ]+ , [Ag3 (H)(BH4 )(dpam)3 ]+ , [Ag3 (BH4 )2 (dpam)3 ]+ , [Ag3 (H)(Cl)(dpam)3 ]+ , and [Ag3 (I)(BH4 )(dpam)3 ]+ , as established by ESI-MS. Use of NaBD4 confirmed that borohydride is the source of the hydride in these clusters. An Orbitrap Fusion LUMOS mass spectrometer was used to explore the gas-phase unimolecular chemistry of selected clusters via multistage mass spectrometry (MSn ) experiments employing low-energy collision-induced dissociation (CID) and high-energy collision-induced dissociation (HCD) experiments. The borohydride containing clusters fragment via two competing pathways: (i) ligand loss and (ii) B-H bond activation involving BH3 loss. Density functional theory (DFT) calculations were used to calculate the energetics of the optimized structures for all precursor ions, fragment ions, and neutrals and to estimate the reaction endothermicities. Generally, there is reasonable agreement between the most abundant product ion formed and the predicted endothermicity of the associated reaction channel. The DFT calculations predicted that the novel dimer [Ag2 (BH4 )(dpam)2 ]+ has a paddlewheel structure in which the dpam and BH4 - ligands bridge both silver centers.

Iridium-catalysed 3,5-bis-borylation of phthalonitrile enables access to a family of C4h octaarylphthalocyanines.

Ir-catalysed borylation of phthalonitrile produces both 4-(Bpin)phthalonitrile (1) and 3,5-bis(Bpin)phthalonitrile (2), which are potential divergent intermediates for the synthesis of functionalized phthalocyanines. To exemplify the utility of 2, we have prepared a series of 3,5-bis-arylphthalonitriles that in turn undergo sterically controlled regioselective cyclotetramization to give previously unknown C4h 1,3,8,10,15,17,22,24-octaarylphthalocyanines.

Bulky bis(aryl)triazenides: just aspiring amidinates? A structural and spectroscopic study.

The synthesis and molecular structures (by single crystal X-ray diffraction) of s-, p- and d-metal complexes of the sterically demanding N,N'-bis(2,6-diisopropylphenyl)triazenide are reported and the spectroscopic (NMR spectroscopy and infrared spectroscopy) and physical properties of these complexes compared to related formamidinate complexes. Through the use of infrared spectroscopy the σ-donor capacity of this ligand is demonstrated to be reduced relative to the structurally isomorphous formamidinate congener, which supports previously advanced theoretical calcluations and DFT results reported herein. These electronic differences are highlighted by the stark contrast in reaction outcomes at rhodium; where [(Dipp2N3)Rh(CO)2] (1) is an isolable, stable complex and the formamidinate complex is not. The coordination chemistry of the triazenide ligand for the s-block metal complexes (M = Li, Na, K) has been shown to give structurally isomorphous complexes to the formamidinate analogue. In contrast to the amidinate complexes, these complexes show extreme lability of coordinated, volatile Lewis-bases, which in turn-yields the highly insoluble base-free triazenide complexes. These complexes are also synthesized directly in the absence of donor solvents. This triazenide ligand has proven to be a suitable ligand for stabilising reactive main group hydrides of Group 13 (M = Ga, In) and attempts at the analogous thallium hydride complex by halide-hydride exchange are reported. Finally attempts at the synthesis of low valent main group complexes are reported ([MIL], M = In, Ga) are also reported, which yield instead disproportionation products ([MIIIXL2], M = Ga, In; [{MIIXL}2], M = Ga).

Tolerant to air σ-alkane complexes by surface modification of single crystalline solid-state molecular organometallics using vapour-phase cationic polymerisation: SMOM@polymer.

Vapour-phase surface-initiated cationic polymerisation of ethylvinylether occurs at single-crystals of the σ-alkane complex [Rh(Cy2PCH2CH2PCy2)(NBA)][BArF4]. This new surface interface makes these normally very air sensitive materials tolerant to air, while also allowing for onward single-crystal to single-crystal reactivity at metal sites within the lattice.

Mechanistic Studies of the Palladium-Catalyzed Desulfinative Cross-Coupling of Aryl Bromides and (Hetero)Aryl Sulfinate Salts.

Pyridine and related heterocyclic sulfinates have recently emerged as effective nucleophilic coupling partners in palladium-catalyzed cross-coupling reactions with (hetero)aryl halides. These sulfinate reagents are straightforward to prepare, stable to storage and coupling reaction conditions, and deliver efficient reactions, thus offering many advantages, compared to the corresponding boron-derived reagents. Despite the success of these reactions, there are only scant details of the reaction mechanism. In this study, we use structural and kinetic analysis to investigate the mechanism of these important coupling reactions in detail. We compare a pyridine-2-sulfinate with a carbocyclic sulfinate and establish different catalyst resting states, and turnover limiting steps, for the two classes of reagent. For the carbocyclic sulfinate, the aryl bromide oxidative addition complex is the resting state intermediate, and transmetalation is turnover-limiting. In contrast, for the pyridine sulfinate, a chelated Pd(II) sulfinate complex formed post-transmetalation is the resting-state intermediate, and loss of SO2 from this complex is turnover-limiting. We also investigated the role of the basic additive potassium carbonate, the use of which is crucial for efficient reactions, and deduced a dual function in which carbonate is responsible for the removal of free sulfur dioxide from the reaction medium, and the potassium cation plays a role in accelerating transmetalation. In addition, we show that sulfinate homocoupling is responsible for converting Pd(OAc)2 to a catalytically active Pd(0) complex. Together, these studies shed light on the challenges that must be overcome to deliver improved, lower temperature versions of these synthetically important processes.

Identification of the Side Products That Diminish the Yields of the Monoamidated Product in Metal-Catalyzed C-H Amidation of 2-Phenylpyridine with Arylisocyanates.

The Ru(II)-catalyzed amidation of 2-arylpyridines with aryl isocyanates via C-H bond activation is less efficient than described previously, due to the formation of a series of side products, which were readily identified using direct infusion electrospray mass spectrometry and high-performance liquid chromatography-mass spectrometry.

Synthesis of Highly Fluorinated Arene Complexes of [Rh(Chelating Phosphine)]+ Cations, and their use in Synthesis and Catalysis.

The synthesis of rhodium complexes with weakly binding highly fluorinated benzene ligands is described: 1,2,3-F3 C6 H3 , 1,2,3,4-F4 C6 H2 and 1,2,3,4,5-F5 C6 H are shown to bind with cationic [Rh(Cy2 P(CH2 )x PCy2 )]+ fragments (x=1, 2). Their structures and reactivity with alkenes, and use in catalysis for promoting the Tishchenko reaction of a simple aldehyde, are demonstrated. Key to the synthesis of these complexes is the highly concentrated reaction conditions and use of the [Al{OC(CF3 )3 }4 ]- anion.

Structural characterization and gas-phase studies of the [Ag10H8(L)6]2+ nanocluster dication.

The reactions between silver salts and borohydrides produce a rich set of products that range from discrete mononuclear compounds through to silver nanoparticles and colloids. Previous studies using electrospray ionization mass spectrometry (ESI-MS) to track the cationic products in solutions containing sodium borohydride, silver(i) tetrafluoroborate and the bisphosphine ligands, L, bis(diphenylphosphino)methane (dppm) and bis(diphenylphosphino)amine (dppa) have identified the dications [Ag10H8(L)6]2+. Here we isolate and structurally characterize [Ag10H8(dppa)6](BF4)2, and [Ag10H8(dppa)6](NO3)2via X-ray crystallography. Both dications have nearly identical structural features consisting of a Ag10 scaffold with the atoms lying on vertices of a bicapped square antiprism. DFT calculations were carried out to suggest potential sites for the hydrides. Ion-mobility mass spectrometry experiments revealed that [Ag10H8(dppa)6]2+ and [Ag10H8(dppm)6]2+ have similar collision cross sections, while multistage mass spectrometry experiments were used to compare their unimolecular gas-phase chemistry. Although the same initial sequential ligand loss followed by cluster fission and H2 evolution is observed, the more acidic N-H of the dppa provides a more labile H for H2 loss and H/D scrambling processes as revealed by isotope labelled experiments.

Kinetic stabilization of low-oxidation state and terminal hydrido main group metal complexes by a sterically demanding N,N'-bis(2,6-terphenyl)triazenide.

A sterically demanding N,N'-bis(2,6-terphenyl)triazenide was employed to stabilize a number of low-coordinate main group metal terminal hydride complexes. These complexes display enhanced thermal stabilities relative to analogous complexes ligated by ß-diketiminates, which we attribute to the steric shielding of the metal hydride moiety by the ligand. We also show this triazenide ligand can stabilize low-oxidation state Group 13 metals. DFT calculations conducted on these triazenide ligated Group 13 metal(i) complexes revealed they possess a narrower HOMO-LUMO gap relative to analogous complexes ligated by other monoanionic N,N'-ligands. In addition, several heteroleptic Group 13 metal(iii) and Group 14 metal(ii) complexes featuring this triazenide are reported.

Room Temperature Acceptorless Alkane Dehydrogenation from Molecular σ-Alkane Complexes.

The non-oxidative catalytic dehydrogenation of light alkanes via C-H activation is a highly endothermic process that generally requires high temperatures and/or a sacrificial hydrogen acceptor to overcome unfavorable thermodynamics. This is complicated by alkanes being such poor ligands, meaning that binding at metal centers prior to C-H activation is disfavored. We demonstrate that by biasing the pre-equilibrium of alkane binding, by using solid-state molecular organometallic chemistry (SMOM-chem), well-defined isobutane and cyclohexane σ-complexes, [Rh(Cy2PCH2CH2PCy2)(η:η-(H3C)CH(CH3)2][BArF4] and [Rh(Cy2PCH2CH2PCy2)(η:η-C6H12)][BArF4] can be prepared by simple hydrogenation in a solid/gas single-crystal to single-crystal transformation of precursor alkene complexes. Solid-gas H/D exchange with D2 occurs at all C-H bonds in both alkane complexes, pointing to a variety of low energy fluxional processes that occur for the bound alkane ligands in the solid-state. These are probed by variable temperature solid-state nuclear magnetic resonance experiments and periodic density functional theory (DFT) calculations. These alkane σ-complexes undergo spontaneous acceptorless dehydrogenation at 298 K to reform the corresponding isobutene and cyclohexadiene complexes, by simple application of vacuum or Ar-flow to remove H2. These processes can be followed temporally, and modeled using classical chemical, or Johnson-Mehl-Avrami-Kologoromov, kinetics. When per-deuteration is coupled with dehydrogenation of cyclohexane to cyclohexadiene, this allows for two successive KIEs to be determined [kH/kD = 3.6(5) and 10.8(6)], showing that the rate-determining steps involve C-H activation. Periodic DFT calculations predict overall barriers of 20.6 and 24.4 kcal/mol for the two dehydrogenation steps, in good agreement with the values determined experimentally. The calculations also identify significant C-H bond elongation in both rate-limiting transition states and suggest that the large kH/kD for the second dehydrogenation results from a pre-equilibrium involving C-H oxidative cleavage and a subsequent rate-limiting ß-H transfer step.

Dehydropolymerization of H3B·NMeH2 Using a [Rh(DPEphos)]+ Catalyst: The Promoting Effect of NMeH2.

[Rh(κ2-PP-DPEphos){η2η2-H2B(NMe3)(CH2)2 tBu}][BArF 4] acts as an effective precatalyst for the dehydropolymerization of H3B·NMeH2 to form N-methylpolyaminoborane (H2BNMeH) n . Control of polymer molecular weight is achieved by variation of precatalyst loading (0.1-1 mol %, an inverse relationship) and use of the chain-modifying agent H2: with M n ranging between 5 500 and 34 900 g/mol and D between 1.5 and 1.8. H2 evolution studies (1,2-F2C6H4 solvent) reveal an induction period that gets longer with higher precatalyst loading and complex kinetics with a noninteger order in [Rh]TOTAL. Speciation studies at 10 mol % indicate the initial formation of the amino-borane bridged dimer, [Rh2(κ2-PP-DPEphos)2(µ-H)(µ-H2BN=HMe)][BArF 4], followed by the crystallographically characterized amidodiboryl complex [Rh2(cis-κ2-PP-DPEphos)2(σ,µ-(H2B)2NHMe)][BArF 4]. Adding ∼2 equiv of NMeH2 in tetrahydrofuran (THF) solution to the precatalyst removes this induction period, pseudo-first-order kinetics are observed, a half-order relationship to [Rh]TOTAL is revealed with regard to dehydrogenation, and polymer molecular weights are increased (e.g., M n = 40 000 g/mol). Speciation studies suggest that NMeH2 acts to form the  precatalysts [Rh(κ2-DPEphos)(NMeH2)2][BArF 4] and [Rh(κ2-DPEphos)(H)2(NMeH2)2][BArF 4], which were independently synthesized and shown to follow very similar dehydrogenation kinetics, and produce polymers of molecular weight comparable with [Rh(κ2-PP-DPEphos){η2-H2B(NMe3)(CH2)2 tBu}][BArF 4], which has been doped with amine. This promoting effect of added amine in situ is shown to be general in other cationic Rh-based systems, and possible mechanistic scenarios are discussed.

Structural diversity in a homologous series of donor free alkali metal complexes bearing a sterically demanding triazenide.

The reactivity of the sterically demanding triazene Dmp-N[double bond, length as m-dash]N-N(H)-Dmp (Dmp2N3H, Dmp = 2,6-bis(2,4,6-trimethylphenyl)phenyl) with alkali metal bases and elemental heavy alkali metals has been examined. All reactions afforded the respective alkali metal triazenide complex. The solid-state molecular structures of these complexes display κ2-N,N'-chelation of the triazenide by the metal. The coordination sphere of each metal center is further furnished by Mπ-arene interactions to the pendant mesityl groups of the triazenide, which enables each complex to exist as a mononuclear species with complexes of the heavier alkali metals display weak aggregation in solid-state. A heteroleptic dilithium complex, featuring µ-κ1-N,N'-bridging of the triazenide by the two lithium centers, was also characterized.