Proazaphosphatrane Research Articles

Synthesis, Characterizations and Applications of Fluoroazaphosphatranes.

Haloazaphosphatranes are the halogenated parents of proazaphosphatranes, also known as Verkade's superbase. While the synthesis of iodo-, bromo- and chloroazaphosphatranes was reported more than thirty years ago by J. G. Verkade, the first synthesis of fluoroazaphosphatranes was only described in 2018 by Stephan et al. Currently, no common and versatile procedure exists to access fluoroazaphosphatranes platform with different structural characteristics. In this report, a new and simple synthesis of this class of compounds was developed based on the nucleophilic attack of the fluoride anion on chloroazaphosphatrane derivatives with good to high isolated yields for the corresponding fluoroazaphosphatranes (70-92%). The scope of the reaction was widened to fluoroazaphosphatranes bearing various substituents and X-ray molecular structures of two of them are reported. The stability of fluoroazaphosphatranes toward nucleophilic solvents like water has been investigated. As they revealed much more robust cations than their chloroazaphosphatrane parents, their chloride salts were tested as organocatalysts for the formation of cyclic carbonates from epoxides and CO2 . Fluoroazaphosphatranes proved to be both efficient and stable catalytic systems for CO2 conversion with catalytic activities similar to those of azaphosphatranes, and no decomposition of the cation was observed at the end of reaction.

Encapsulation of Azaphosphatranes and Proazaphosphatranes in Confined Spaces.

Proazaphosphatranes (also named Verkade's superbases) and their azaphosphatrane conjugated acids have been recently been shown to be confined in either covalent or self-assembled molecular cages, or immobilized in nanopores of hybrid materials. The encapsulation of these phosphorus moieties turns out to strongly affect both their acid-base, catalytic, and recognition properties. The thermodynamics and kinetics of the proton transfer as well as the selectivity and catalytic activities of Verkade's superbases were strongly changed upon their confinement in a hemicryptophane cavity. Moreover, self-assembled cages, including azaphosphatrane moieties, were found to display remarkable anion recognition properties in water. In this Minireview, these new aspects of the chemistry of aza- and proaza-phosphatranes are presented, in order to highlight the great potential of such an approach.

Using frustrated Lewis pairs to explore C-F bond activation.

Our interest in C-F bond activation prompted an investigation of the reactions of PhC(O)CF3 with a superbasic proazaphosphatrane (Verkade's base) and a corresponding FLP. The reaction of PhC(O)CF3 with P(MeNCH2CH2)3N in a 2 : 1 ratio generates [FP(NMeCH2CH2)3N][PhC(O)CF2COCF3Ph]. While this salt was not isolable, the anion could be derivatized to allow the isolation of [PhC(O)CF2C(OSiMe2tBu)CF3Ph], 1. To further probe this C-F bond activation, the FLP P(MeNCH2CH2)3N/BPh3 was allowed to react with PhC(O)CF3, which afforded the salt [PhC(CF2)OP(MeNCH2CH2)3N][FBPh3], 2. Insights into the mechanism of the reaction of the proazaphosphatrane with PhC(O)CF3 have emerged from the reactivity of 2 and these have been augmented by DFT computations. Salt 2 could be readily converted to the triflate derivative 3, which was a viable synthon for further C-F bond reactivity. Sequential reaction with Na[HBEt3] afforded the salts [PhC(CF(H))OP(MeNCH2CH2)3N][O3SCF3], 4 and [PhC(CH2)OP(MeNCH2CH2)3N][O3SCF3], 5. Interestingly, the formation of 5 contrasts with the formation of [HP(MeNCH2CH2)3N][PhC(CH2)OB(C6F5)3], 6 observed following the reaction of the FLP P(MeNCH2CH2)3N/B(C6F5)3 with PhC(O)Me. Thus these differing FLP protocols provide avenues to salts containing either an enolate derived cation or anion.

Enantiopure encaged Verkade's superbases: Synthesis, chiroptical properties, and use as chiral derivatizing agent.

Verkade's superbases, entrapped in the cavity of enantiopure hemicryptophane cages, have been synthesized with enantiomeric excess (ee) superior to 98%. Their absolute configuration has been determined by using electronic circular dichroism (ECD) spectroscopy. These enantiopure encaged superbases turned out to be efficient chiral derivatizing agents for chiral azides, underlining that the chirality of the cycloveratrylene (CTV) macrocycle induces different magnetic and chemical environments around the phosphazide functions.

Frustrated Lewis Pair Oxidation Permits Synthesis of a Fluoroazaphosphatrane, [FP(MeNCH2CH2)3N

Proazaphosphatranes, also known as Verkade's superbases, are among the strongest nonionic bases available. Their extreme basicity derives in part from their ability to form a P-N transannulation upon interaction of the P atom with an electrophile. Although haloazaphosphatrane cations of the form [XP(RNCH2CH2)3N]+ have previously been reported for X = Cl, Br, and I, no fluoroazaphosphatranes (X = F) have been prepared. Unlike treatment with Cl2, Br2, I2, and surrogates thereof, reaction of proazaphosphatranes with XeF2 results in decomposition. Analysis of the decomposition products suggested that fluoride ions may be the destructive agent. However, oxidation of a proazaphosphatrane/BPh3 frustrated Lewis pair affords [FP(RNCH2CH2)3N][FBPh3]. Systematic trends in the experimental and computed NMR and structural data are considered. A computational analysis suggests that the transannular P-N distance varies as a result of the flexibility of the molecules and their capacity to deform in the solid state.

Verkade's Superbase as an Organocatalyst for the Strecker Reaction

Proazaphosphatranes ‐Verkade's superbases‐ proved to be efficient organocatalysts for the Strecker reaction between protected imines and trimethylsilyl cyanide (TMSCN). Excellent to quantitative yields were reached and, compared to other systems, only low catalyst loading and short reaction times were required for the reaction to proceed efficiently. A remarkable initial turnover frequency (TOF), close to 105 h–1, was achieved, associated with an excellent selectivity since no side reactions were observed. A reaction mechanism was proposed and the key role played by the apical nitrogen in the proazaphosphatrane structure was demonstrated.

Endohedral Functionalized Cage as a Tool to Create Frustrated Lewis Pairs.

A frustrated Lewis pair (FLP) system was obtained by confinement of the Lewis base partner, a Verkade's superbase, in a molecular cavity. Whereas the model superbase lacking cavity displayed no catalytic activity in Morita-Baylis-Hillman (MBH) reactions, when associated to titanium (IV) chloride, the encaged superbase turns out to be an efficient catalyst under the same conditions. The crucial role of the endohedral functionalized cage on catalytic performance was further demonstrated by the fact that model superbases with bulky substituents were much less efficient to produce active catalysts, as well as by inhibition and substrate selection experiments. 31 P NMR spectroscopy and mass spectrometry experiments evidenced that no interaction between the Lewis acidic and basic partners occurred when the superbase was capped by a cycloveratrylene (CTV) unit, thus creating a true FLP active system.

Endohedral Functionalized Cage as a Tool to Create Frustrated Lewis Pairs

AbstractA frustrated Lewis pair (FLP) system was obtained by confinement of the Lewis base partner, a Verkade's superbase, in a molecular cavity. Whereas the model superbase lacking cavity displayed no catalytic activity in Morita–Baylis–Hillman (MBH) reactions, when associated to titanium (IV) chloride, the encaged superbase turns out to be an efficient catalyst under the same conditions. The crucial role of the endohedral functionalized cage on catalytic performance was further demonstrated by the fact that model superbases with bulky substituents were much less efficient to produce active catalysts, as well as by inhibition and substrate selection experiments. 31P NMR spectroscopy and mass spectrometry experiments evidenced that no interaction between the Lewis acidic and basic partners occurred when the superbase was capped by a cycloveratrylene (CTV) unit, thus creating a true FLP active system.

Organocatalyzed Anionic Ring-Opening Polymerizations of N-Sulfonyl Aziridines with Organic Superbases.

The anionic ring-opening polymerizations (AROPs) of N-sulfonyl aziridines, in the presence of organic superbases including phosphazene (t-Bu-P4), Verkade's base (P(i-PrNCH2CH2)3N, TiPP), DBU, MTBD, and N,N,N',N'-tetramethylguanidine (TMG), using N-benzyl-p-toluenesulfonamide (BnN(H)Ts) as initiator were explored to produce metal-free poly(sulfonylaziridine)s. Among the superbases used, the catalytic activity was found directly proportional to their basicity. Remarkably, t-Bu-P4 and TiPP gave a living/controlled AROP of 2-methyl-N-tosylaziridine (TsMAz), where t-Bu-P4 performed better, affording the metal-free and well-defined poly(sulfonylaziridine)s with high molar masses (Mn(SEC) > 30 kg mol-1) and low dispersities (Đ < 1.10) in 3.5 h. For the less reactive monomers of 2-methyl-N-ethylsulfonyl aziridine (EsMAz) and 2-phenyl-N-tosylaziridine (TsPhAz), t-Bu-P4 showed the same excellent catalytic efficiency (30 equiv, conv. > 95%, 5 h). The organocatalyzed AROP allowed the use of lower catalyst (t-Bu-P4) loading than the amount of initiator (BnN(H)Ts), but the propagating polymer chains were as many as the number of equivalents of the introduced initiators, which could lower the loading of catalyst used to amounts as low as 0.05 mol %.

Synthesis of Gold(I) Complexes Bearing Verkade's Superbases

Proazaphosphatranes, also known as Verkade's superbases, have been investigated as ligands for gold(I). If the coordination to the gold center by the phosphorus atom suggests phosphine‐like behavior, gold(I)‐containing Verkade's superbase complexes could also be prepared from the weak conjugate acid azaphosphatrane by the formation of the corresponding silver complex and subsequent transmetalation to gold, similarly to the synthetic route used for complexes bearing N‐heterocyclic carbene ligands (NHCs). A competitive transmetalation experiment highlighted the higher lability of Verkade's superbases compared with NHCs. Furthermore, combined theoretical and experimental studies showed that they display strong σ‐donor ability, better than phosphines and similar to NHCs. Thus, some specific properties of both NHCs and phosphines are combined in Verkade's superbases, thereby providing a new approach to tuning the ligand properties of gold(I) complexes.

Complete Series of Alkali-Metal M(BH3NH2BH2NH2BH3) Hydrogen-Storage Salts Accessed via Metathesis in Organic Solvents.

We report a new efficient way of synthesizing high-purity hydrogen-rich M(BH3NH2BH2NH2BH3) salts (M = Li, Na, K, Rb, Cs). The solvent-mediated metathetic synthesis applied here uses precursors containing bulky organic cations and weakly coordinating anions. The applicability of this method permits the entire series of alkali-metal M(BH3NH2BH2NH2BH3) salts (M = Li, Na, K, Rb, Cs) to be obtained, thus enabling their comparative analysis in terms of crystal structures and hydrogen-storage properties. A novel polymorphic form of Verkade's base (C18H39N4PH)(BH3NH2BH2NH2BH3) precursor was also characterized structurally. For all compounds, we present a comprehensive structural, spectroscopic, and thermogravimetric characterization (PXRD, NMR, FTIR, Raman, and TGA/DSC/MS).

Incorporation of Pendant Bases into Rh(diphosphine)2 Complexes: Synthesis, Thermodynamic Studies, And Catalytic CO2 Hydrogenation Activity of [Rh(P2N2)2]+ Complexes

A series of five [Rh(P2N2)2](+) complexes (P2N2 = 1,5-diaza-3,7-diphosphacyclooctane) have been synthesized and characterized: [Rh(P(Ph)2N(Ph)2)2](+) (1), [Rh(P(Ph)2N(Bn)2)2](+) (2), [Rh(P(Ph)2N(PhOMe)2)2](+) (3), [Rh(P(Cy)2N(Ph)2)2](+) (4), and [Rh(P(Cy)2N(PhOMe)2)2](+) (5). Complexes 1-5 have been structurally characterized as square planar rhodium bis-diphosphine complexes with slight tetrahedral distortions. The corresponding hydride complexes 6-10 have also been synthesized and characterized, and X-ray diffraction studies of HRh(P(Ph)2N(Bn)2)2 (7), HRh(P(Ph)2N(PhOMe)2)2 (8) and HRh(P(Cy)2N(Ph)2)2 (9) show that the hydrides have distorted trigonal bipyramidal geometries. Equilibration of complexes 2-5 with H2 in the presence of 2,8,9-triisopropyl-2,5,8,9-tetraaza-1-phosphabicyclo[3,3,3]undecane (Verkade's base) enabled the determination of the hydricities and estimated pKa's of the Rh(I) hydride complexes using the appropriate thermodynamic cycles. Complexes 1-5 were active for CO2 hydrogenation under mild conditions, and their relative rates were compared to that of [Rh(depe)2](+), a nonpendant-amine-containing complex with a similar hydricity to the [Rh(P2N2)2](+) complexes. It was determined that the added steric bulk of the amine groups on the P2N2 ligands hinders catalysis and that [Rh(depe)2](+) was the most active catalyst for hydrogenation of CO2 to formate.

Catalytic activity of an encaged Verkade's superbase in a base-catalyzed Diels-Alder reaction.

Organocatalysis in a confined space has been performed through encapsulation of a proazaphosphatrane superbase in a hemicryptophane host. The resulting catalyst displays good to high catalytic activity in the base-catalyzed Diels-Alder reactions investigated. A comparison with the model superbase, which lacks a cavity, shows much higher diastereomeric excess with the encaged proazaphosphatrane for the reaction of 3-hydroxy-2-pyrone with N-methylmaleimide. The use of an encaged superbase as organocatalyst is unprecedented and highlights how the confinement may impact the stereoselectivity.

Ligand-Based Carbon–Nitrogen Bond Forming Reactions of Metal Dinitrosyl Complexes with Alkenes and Their Application to C–H Bond Functionalization

Over the past few decades, researchers have made substantial progress in the development of transition metal complexes that activate and functionalize C-H bonds. For the most part, chemists have focused on aliphatic and aromatic C-H bonds and have put less effort into complexes that activate and functionalize vinylic C-H bonds. Our groups have recently developed a novel method to functionalize vinylic C-H bonds that takes advantage of the unique ligand-based reactivity of a rare class of metal dinitrosyl complexes. In this Account, we compare and discuss the chemistry of cobalt and ruthenium dinitrosyl complexes, emphasizing alkene binding, C-H functionalization, and catalysis. Initially discovered in the early 1970s by Brunner and studied more extensively in the 1980s by the Bergman group, the cyclopentadienylcobalt dinitrosyl complex CpCo(NO)2 reacts reversibly with alkenes to give, in many cases, stable and isolable cobalt dinitrosoalkane complexes. More recently, we found that treatment with strong bases, such as lithium hexamethyldisilazide, Verkade's base, and phosphazene bases, deprotonates these complexes and renders them nucleophilic at the carbon α to the nitroso group. This conjugate anion of metal dinitrosoalkanes can participate in conjugate addition to Michael acceptors to form new carbon-carbon bonds. These functionalized cobalt complexes can further react through alkene exchange to furnish the overall vinylic C-H functionalized organic product. This stepwise sequence of alkene binding, functionalization, and retrocycloaddition represents an overall vinylic C-H functionalization reaction of simple alkenes and does not require directing groups. We have also developed an asymmetric variant of this reaction sequence and have used this method to synthesize C1- and C2-symmetric diene ligands with high enantioinduction. Building upon these stepwise reactions, we eventually developed a simple one-pot procedure that uses stoichiometric amounts of a cobalt dinitrosoalkane complex for both inter- and intramolecular C-H functionalization. We can achieve catalysis in one-pot intramolecular reactions with a limited range of substrates. Our groups have also reported an analogous ruthenium dinitrosyl complex. In analogy to the cobalt complex, this ruthenium complex reacts with alkenes in the presence of neutral bidentate ligands, such as TMEDA, to give octahedral dinitrosoalkane complexes. Intramolecular functionalization or cyclization of numerous ruthenium dinitrosoalkane complexes proceeds under mild reaction conditions to give the functionalized organic products in excellent yields. However, despite extensive efforts, so far we have not been able to carry out intermolecular reactions of these complexes with a variety of electrophiles or C-H functionalization reactions. Although additional work is necessary to further boost the catalytic capabilities of both cobalt and ruthenium dinitrosyl complexes for vinylic C-H functionalization of simple alkenes, we believe this ligand-based vinylic C-H functionalization reaction has provided chemists with a useful set of tools for organic synthesis.

Homogeneous and silica-supported azidoproazaphosphatranes as efficient catalysts for the synthesis of substituted coumarins

Homogeneous and silica-supported azidoproazaphosphatranes derived from the Verkade's superbase catalyze the synthesis of substituted coumarins with moderate to good yields and high selectivity.

Syntheses and Structural Characterizations of Anionic Borane-Capped Ammonia Borane Oligomers: Evidence for Ammonia Borane H2 Release via a Base-Promoted Anionic Dehydropolymerization Mechanism

Studies of the activating effect of Verkade's base, 2,8,9-triisobutyl-2,5,8,9-tetraaza-1-phosphabicyclo[3.3.3]undecane (VB), on the rate and extent of H(2) release from ammonia borane (AB) have led to the syntheses and structural characterizations of three anionic aminoborane chain-growth products that provide direct support for anionic dehydropolymerization mechanistic steps in the initial stages of base-promoted AB H(2) release reactions. The salt VBH(+)[H(3)BNH(2)BH(2)NH(2)BH(3)](-) (1) containing a linear five-membered anionic aminoborane chain was produced in 74% yield via the room-temperature reaction of a 3:1 AB/VB mixture in fluorobenzene solvent, while the branched and linear-chain seven-membered anionic aminoborane oligomers VBH(+)[HB(NH(2)BH(3))(3)](-) (2a) and VBH(+)[H(3)BNH(2)BH(2)NH(2)BH(2)NH(2)BH(3)](-) (2b) were obtained from VB/AB reactions carried out at 50 °C for 5 days when the AB/VB ratio was increased to 4:1. X-ray crystal structure determinations confirmed that these compounds are the isoelectronic and isostructural analogues of the hydrocarbons n-pentane, 3-ethylpentane, and n-heptane, respectively. The structural determinations also revealed significant interionic B-H···H-N dihydrogen-bonding interactions in these anions that could enhance dehydrocoupling chain-growth reactions. Such mechanistic pathways for AB H(2) release, involving the initial formation of the previously known [H(3)BNH(2)BH(3)](-) anion followed by sequential dehydrocoupling of B-H and H-N groups of growing borane-capped aminoborane anions with AB, are supported by the fact that 1 was observed to react with an additional AB equivalent to form 2a and 2b.

Encaging the Verkade’s Superbases: Thermodynamic and Kinetic Consequences

Proazaphosphatranes, also known as Verkade's superbases, are nonionic species, which exhibit catalytic properties for a wide range of reactions. The properly designed host molecule 3 and its protonated counterpart [3·H](+)Cl(-) were synthesized to study how confinement can modify the stability and the reactivity of a Verkade's superbase. The results show that the encapsulation does not alter the strong basicity of the proazaphosphatrane, but dramatically decreases the rate of proton transfer.

Verkade super base-catalysed transesterification of propylene carbonate with methanol to co-produce dimethyl carbonate and propylene glycol

The co-generation of dimethyl carbonate (potential fuels additive, environmentally friendly replacement for more toxic methylating agents, etc.) and propylene glycol via the transesterification reaction of propylene carbonate and methanol was studied using base catalysis. Verkade super bases (proazaphosphatranes) proved especially effective at low catalyst loadings (0.5%) for the rapid transesterification of propylene carbonate with methanol under mild conditions and with high product selectivity (typically >99.5%). These bases neatly avoid the use of alkoxide catalysts which generate by-products in their neutralisation. The kinetics of the reactions were studied using data obtained from in situ NMR reaction monitoring. The influences of several reaction optimisation parameters are also dealt with.

Basicity of exceedingly strong non-ionic organic bases in acetonitrile —Verkade's superbase and some related phosphazenes

The basicity of Verkade's superbase (12) in MeCN solution is considered by a quite accurate theoretical model. It is shown that the corresponding pKa value is 29.0. Hence, its basicity is comparable or higher than that of some other P1 phosphazenes, but it is lower than the basicity of P2 phosphazenes. Structural characteristics of Verkade's superbase and its conjugate acid, as well as the origin of its pronounced basicity, are briefly discussed. Extended Verkade's superbase 13 and some Janus-type phosphazenes are examined too. It is shown that they are very good candidates for even stronger neutral organic superbases. A very useful by-product of the present study are quite accurate estimates of the gas phase proton affinities of some P1, P2, P3 and P4 polyaminophosphazenes obtained by the B3LYP/6-311+G(2df,p)//B3LYP/6-31G* scheme. The latter was successfully tested against G2 results on small molecules. This is of importance, because the experimentally measured gas phase values for phosphazenes are not available, implying that the theoretical data fill this gap with reliable information.

Development of catalysts for the Baylis–Hillman reaction: the application of tetramethylguanidine and attempts to use a supported analogue

We show here that tetramethylguanidine (TMG) is a useful catalyst for the Baylis–Hillman reaction of aldehydes with methyl acrylate, showing good activity with a range of aldehyde substrates and, unlike many other catalysts or catalyst mixtures, it can be used to good effect with simple aliphatic aldehydes. We show that the activity of the catalyst is decreased when the reaction is run using solvents rather than solvent-free but, in the case where a solvent is necessary, dichloromethane offers the best results. Attempts to use supported or derivatised TMG complexes as catalysts for the reaction have been unsuccessful suggesting that the presence of an amine hydrogen is key to the activity of TMG. Attempts to use stabilised aliphatic phosphines as catalysts for the reaction have proven partly successful, with only modest yields of product being obtained with 2-(dicyclohexylphosphino)biphenyl and 2-(di-tert-butylphosphino)biphenyl. The Verkade superbase, P(MeNCH2CH2)3N, proved inactive as a catalyst, an adduct with the acrylate being the only product formed.