Atroposelective Arene-Forming Wittig Reaction by Phosphorus PIII/PV=O Redox Catalysis.

The Wittig reaction is renowned as exceptionally versatile method for converting a diversity of aldehydes and ketones into alkenes. Recently, strategies for chiral phosphine catalysis under PIII/PV=O redox cycling emerged to render this venerable transformation stereoselective. Herein, we describe that phosphine redox catalysis enables the enantioselective synthesis of pertinent biaryl atropisomers by means of a stereocontrolled arene-forming Wittig reaction. Key to the process is the release of an endogenous base from readily accessible tert-butyloxycarbonylated Morita-Baylis-Hillman adducts triggered by catalyst intramolecularization, permitting mild phosphine redox catalysis for atroposelective Wittig reactions. By this strategy, a broad diversity of biaryl atropisomers is obtained with up to 94:6 enantioselectivity.

Dialumene-Mediated Production of Phosphines through P4 Reduction.

The formation of phosphorus-rich alanes featuring butterfly-like geometries is achieved. The two-electron reduction products feature a unique P4 2- structure and can act as a source of P3-. The treatment of these phosphorus containing products with electrophiles under mild conditions results in the formation of different phosphines. This approach eliminates the need for high temperatures and/or high pressures, which are commonly required in industrial processes for the preparation of useful phosphines.The activation and further functionalization of white phosphorus (P4) by main group complexes has become an increasingly studied topic in recent times. Herein, we report the controlled formation of phosphorus-rich alanes featuring butterfly-like geometries from the selective reaction of P4 with dialumenes, ([L(IiPr)Al]2) (1: L=Tripp=2,4,6-iPr3C6H2; 2: L=tBu2MeSi; IiPr=[MeCN(iPr)]2C)). The two-electron-reduction product of P4 features a P4 2- structure and is shown to be able to act as a source of P3-. Treatments of different electrophiles (e.g., chlorotrimethylsilane (Me3SiCl), iodotrimethylsilane (Me3SiI), HCl, or acetyl chloride (CH3COCl)) with these alanes under mild conditions gave the corresponding phosphines (e.g., P(SiMe3)3, PH3, or P(COCH3)3).

Control over Anion Coordination on Pd(II), Cu(I), and Ag(I) with Regioisomeric Phosphine-Carboxylate Ligands.

The coordination of anionic donors is involved at various stages of catalytic cycles in transition-metal catalysis, but control over the spatial positioning of anions around a metal center is a challenge in coordination chemistry. Here we show that regioisomeric phosphine-carboxylate ligands provide spatial anion control on palladium(II) centers by favoring either κ2, cis-κ1, or trans-κ1 coordination of the carboxylate donor. Additionally, the palladium(II) carboxylates, which contain a methyl donor, upon protonation, deliver metal-alkyl complexes that feature a coordinated carboxylic acid. Such complexes can be considered as models for the minima that follow the concerted metalation-deprotonation transition state for C-H activation. The predictability of the coordination modes is further demonstrated on silver(I) and copper(I) centers, for which less common structures of mononuclear and dinuclear complexes can be obtained by using spatial anion control. Our results demonstrate the potential for spatial control over carboxylate anions in coordination chemistry.

Ligand Centered Reactivity of a Transition Metal Bound Geometrically Constrained Phosphine.

The electronic properties, coordination chemistry and reactivity of metal complexes of a planar (C2v symmetric) acridane-derived geometrically constrained phosphine, P(NNN), are described. On complexation to metal centers, the phosphine was found to adopt a distorted trigonal pyramidal structure with a high barrier to pyramidal inversion (22.3 kcal/mol at 298 K for Au[P(NNN)]Cl). Spectroscopic data and theoretical calculations carried out at the density functional level of theory indicate that P(NNN) is a moderate σ-donor, with significant π-acceptor properties. Despite the distortion undergone by the phosphorus atom on coordination to metal centers, the P(NNN) ligand retains its ability to react with small molecule substrates with polar E-H bonds (MeOH, NH2Ph, NH3). It does so in a concerted fashion across one of the P-N bonds, and reversibly in the case of amine substrates. This cooperative bond activation chemistry may ultimately prove beneficial in catalysis.

Enantioselective Rhodium-Catalyzed C-H Arylation Enables Direct Synthesis of Atropisomeric Phosphines.

Atropisomeric phosphines hold considerable significance in asymmetric catalysis, yet their synthesis presents a formidable challenge owing to intricate multistep procedures. In this context, a groundbreaking methodology has been presented for their preparation. This innovative approach entails an atroposelective rhodium-catalyzed C-H activation employing aryl and heteroaryl halides, chelated by a P(III) center. The essence of this strategy lies in its ability to directly construct chiral phosphine ligands in a single step, thereby exhibiting exceptional efficiency in terms of atom and redox economy. Illustrative examples serve to demonstrate the immense potential of in situ-formed ligands in asymmetric catalysis. Mechanistic experiments have further provided invaluable insights into this transformation.

Phosphine Catalyzed Michael-Type Additions: The Synthesis of Glutamic Acid Derivatives from Arylidene-α-amino Esters.

The reaction of arylidene-α-amino esters with electrophilic alkenes to yield Michael-type addition compounds is optimized using several phosphines as organocatalysts. The transformation is very complicated due to the generation of several final compounds, including those derived from the 1,3-dipolar cycloadditions. For this reason, the selection of the reaction conditions is a very complex task and the slow addition of the acrylic system is very important to complete the process. The study of the variation in the structural components of the starting imino ester is performed as well as the expansion of other electron-poor alkenes. The crude products have a purity higher than 90% in most cases without any purification. A plausible mechanism is detailed based on the bibliography and the experimental results. The synthesis of pyroglutamate entities, after the reduction of the imino group and cyclization, is performed in high yields. In addition, the hydrolysis of the imino group, under acidic media, represents a direct access to glutamate surrogates.

A Continuous-Wave EPR Investigation into the Photochemical Transformations of the Chromium(I) Carbonyl Complex [Cr(CO)4bis(diphenylphosphino)]+ and Reactivity with 1-hexene.

Chromium complexes containing a bis(diphenylphosphino) ligand have attracted significant interest over many years due to their potential as active catalysts for ethylene oligomerisation when combined with suitable co-catalysts such as triethylaluminium (TEA) or methylaluminoxane (MAO). While there has been considerable attention devoted to the possible reaction intermediates and the nature of the Cr oxidation states involved, the potential UV photoactivity of the Cr(I) complexes has so far been overlooked. Therefore, to explore the photoinduced transformations of bis(diphenylphosphino) stabilized Cr(I) complexes, we used continuous-wave (CW) EPR to study the effects of UV radiation on a cationic [Cr(CO)4(dppp)]+[Al(OC(CF3)3)4]- complex (1), where dppp represents the 1,3 bis-(diphenylphosphino)propane ligand, Ph2P(C3H6)PPh2. Our preliminary investigations into the photochemistry of this complex revealed that [Cr(CO)4(dppp)]+ (1) can be readily photo-converted into an intermediate mer-[Cr(CO)3(κ1-dppp)(κ2-dppp)]+ complex (2) and eventually into a trans-[Cr(CO)2(dppp)2]+ complex (3) in solution at room temperature under UV-A light. Here, we show that the intermediate species (2) involved in this transformation can be identified by EPR at much lower temperature (140 K) and at a specific wavelength (highlighting the wavelength dependency of the reaction). In addition, small amounts of a 'piano-stool'-type complex, namely [Cr(CO)2(dppp-η6-arene)]+ (4), can also be formed during the photoconversion of [Cr(CO)4(dppp)]+ using UV-A light. There was no evidence for the formation of the [Cr(L-bis-η6-arene)]+ complex (5) in these UV irradiation experiments. For the first time, we also evidence the formation of a 1-hexene coordinated [Cr(CO)3(dppp)(1-hexene)]+ complex (6) following UV irradiation of [Cr(CO)4(dppp)]+ in the presence of 1-hexene; this result demonstrates the unprecedented opportunity for exploiting light activation during Cr-driven olefin oligomerisation catalysis, instead of expensive, difficult-to-handle, and hazardous chemical activators.

Carboranylphosphines: B9-Substituted Derivatives with Enhanced Reactivity for the Anchoring to Dendrimers.

Several ortho-carboranes bearing a phenoxy or a phenylamino group in the B9 position were prepared employing various protection and deprotection strategies. Following established protocols, dendritic compounds were synthesized from a hexachlorocyclotriphosphazene or thiophosphoryl chloride core, and possible anchoring options for the B9-substituted ortho-carboranes were investigated experimentally and theoretically (DFT). Furthermore, 1- or 1,2-phosphanyl-substituted carborane derivatives were obtained. The resulting diethyl-, diisopropyl-, di-tert-butyl-, diphenyl- or diethoxyphosphines bearing a tunable ortho-carborane moiety are intriguing ligands for future applications in homogeneous catalysis or the medicinal sector.

N-heterocyclic-carbene vs diphosphine auxiliary ligands in thioamidato Cu(I) and Ag(I) complexes towards the development of potent and dual-activity antibacterial and apoptosis-inducing anticancer agents.

Group 11 metal complexes exhibit promising antibacterial and anticancer properties which can be further enhanced by appropriate ligands. Herein, a series of mononuclear thioamidato Cu(I) and Ag(I) complexes bearing either a diphosphine (P^P) or a N-heterocyclic carbene (NHC) auxiliary ligand (L) was synthesized, and the impact of the co-ligand L on the in vitro antibacterial and anticancer properties of their complexes was assessed. All complexes effectively inhibited the growth of various bacterial strains, with the NHC-Cu(I) complex found to be particularly effective against the Gram (+) bacteria (IC50 = 1-4 µg mL-1). Cytotoxicity studies against various human cancer cells revealed their high anticancer potency and the superior activity of the NHC-Ag(I) complex (IC50 = 0.95-4.5 µΜ). Flow cytometric analysis on lung and breast cancer cells treated with the NHC-Ag(I) complex suggested an apoptotic cell-death pathway; molecular docking calculations provided mechanistic insights, proving the capacity of the complex to bind on apoptosis-regulating proteins and affect their functionalities.

Comparison of Monophosphine and Bisphosphine Precatalysts for Ni-Catalyzed Suzuki-Miyaura Cross-Coupling: Understanding the Role of the Ligation State in Catalysis.

Practical advances in Ni-catalyzed Suzuki-Miyaura cross-coupling (SMC) have been limited by a lack of mechanistic understanding of phosphine ligand effects. While bisphosphines are commonly used in these methodologies, we have observed instances where monophosphines can provide comparable or higher levels of reactivity. Seeking to understand the role of ligation state in catalysis, we performed a head-to-head comparison study of C(sp2)-C(sp2) Ni SMCs catalyzed by mono and bisphosphine precatalysts using six distinct substrate pairings. Significant variation in optimal precatalyst was observed, with the monophosphine precatalyst tending to outperform the bisphosphines with electronically deactivated and sterically hindered substrates. Mechanistic experiments revealed a role for monoligated (P1Ni) species in accelerating the fundamental organometallic steps of the catalytic cycle, while highlighting the need for bisligated (P2Ni) species to avoid off-cycle reactivity and catalyst poisoning by heterocyclic motifs. These findings provide guidelines for ligand selection against challenging substrates and future ligand design tailored to the mechanistic demands of Ni-catalyzed SMCs.

Merging Visible Light Photocatalysis and P(III)-Directed C-H Activation by a Single Catalyst: Modular Assembly of P-Alkyne Hybrid Ligands.

Metal-catalyzed C-H activation strategies provide an efficient approach for synthesis by minimizing atom, step, and redox economy. Developing milder, greener, and more effective protocols for these strategies is always highly desirable to the scientific community. In this study, the utilization of a single rhodium complex enabled the visible-light-induced late-stage C-H activation of biaryl-type phosphines with alkynyl bromides, employing inherent phosphorus atoms as directing groups. This chemistry combines P(III)-directed C-H activation with visible light photocatalysis, under exogenous photosensitizer-free conditions, offering a unique platform for ligand design and preparation. Furthermore, this study also explores the asymmetric catalysis and coordination chemistry of the resulting P-alkyne hybrid ligands with specific transition metals. Experimental results and density functional theory calculations demonstrate the mechanistic intricacies of this transformation.

Cross-Electrophile C-PIII Coupling of Chlorophosphines with Organic Halides: Photoinduced PIII and Aminoalkyl Radical Generation Enabled by Pnictogen Bonding.

Pnictogen bonding (PnB) has gained recognition as an appealing strategy for constructing novel architectures and unlocking new properties. Within the synthetic community, the development of a straightforward and much simpler protocol for cross-electrophile C-PIII coupling remains an ongoing challenge with organic halides. In this study, we present a simple strategy for photoinduced PnB-enabled cross-electrophile C-PIII couplings using readily available chlorophosphines and organic halides via merging single electron transfer (SET) and halogen atom transfer (XAT) processes. In this photomediated transformation, the PnB formed between chlorophosphines and alkyl amines facilitates the photogeneration of PIII radicals and α-aminoalkyl radicals through SET. Subsequently, the resulting α-aminoalkyl radicals activate C-X bonds via XAT, leading to the formation of carbon radicals. This methodology offers operational simplicity and compatibility with both aliphatic and aromatic chlorophosphines and organic halides.

Phosphino-Phosphination Reactions: Frustrated Lewis Pair Reactivity of Phosphino-Phosphonium Cations with Alkynes.

The phosphino-phosphonium cations of the form [R3 PPR'2 ]+ are labile and provide access to the constituent Lewis acidic and Lewis basic fragments. This permits frustrated Lewis pair-type addition reactions to alkynes, affording unprecedented phosphino-phosphination reactions and giving cations of the form [cis-R3 PCHC(R'')PR'2 ]+ . This reactivity is further adapted to prepare several examples of a rare class of dissymmetric cis-olefin-linked bidentate phosphines.

Access to Enantiomerically Pure P-Chiral 1-Phosphanorbornane Silyl Ethers.

Sulfur-protected enantiopure P-chiral 1-phosphanorbornane silyl ethers 5a,b are obtained in high yields via the reaction of the hydroxy group of P-chiral 1-phosphanorbornane alcohol 4 with tert-butyldimethylsilyl chloride (TBDMSCl) and triphenylsilyl chloride (TPSCl). The corresponding optically pure silyl ethers 5a,b are purified via crystallization and fully structurally characterized. Desulfurization with excess Raney nickel gives access to bulky monodentate enantiopure phosphorus(III) 1-phosphanorbornane silyl ethers 6a,b which are subsequently applied as ligands in iridium-catalyzed asymmetric hydrogenation of a prochiral ketone and enamide. Better activity and selectivity were observed in the latter case.

Synthesis of Photochromic Phosphines by Pd-Catalyzed Annulation Reaction of Alkynes Bearing Phosphinyl Substituent with a Silacyclopropene.

The synthesis of phosphines with light controlled basicity is presented in this study. A methodological approach for the preparation of these unconventional photochromic phosphines based on a dithienylethene organic moiety is reported. It relies on the palladium-catalyzed annulation of alkynyl phosphines in the presence of a 2,3-Dithienylsilacyclopropene. Accordingly, a diphenyphosphino moiety is connected to the organic photochrome thanks to different linkers. Their influence on the photochromism and on the phosphinyl group basicity is studied and evaluated based on experimental an NMR descriptor as well as DFT calculations.

A General Strategy for Increasing the Air Stability of Phosphines Including Primary Phosphines.

A general approach for increasing the air-stability of various primary phosphines in the absence of kinetic stabilization is presented that contrasts with previous interpretations, which were limited to specific phosphines. This contribution shows the synthesis of a series of air-stable primary phosphines Fc(CH2 )n PH2 , where n=0,1,2,3; and Fc=ferrocenyl, and their corresponding isolable primary phosphine oxides. It was demonstrated that the ferrocene moiety exerts an antioxidant effect on the primary phosphine group, which is intermolecular, solvent dependent and increases with the electron density on the ferrocene moiety. Furthermore, we demonstrated that the presence of ferrocene in solution also inhibits the oxidation of other secondary and tertiary phosphines in air. Together our findings suggest that quenching of singlet oxygen is the actual reason for the antioxidant effect; this was experimentally confirmed by using other established singlet oxygen quenchers, thus demonstrating a key role of singlet oxygen in the aerobic oxidation of phosphines.

Antibactericidal Ir(III) and Ru(II) Complexes with Phosphine-Alkaloid Conjugate and Their Interactions with Biomolecules: A Case of N-Methylphenethylamine.

The phosphine ligand (Ph2 PCH2 N(CH3 )(CH2 )2 Ph, PNMPEA) obtained by the reaction of the (hydroxymethyl)diphenylphosphine with naturally occurring alkaloid N-methylphenethylamine, was used to synthesize the half-sandwich iridium(III) (Ir(η5 -Cp*)Cl2 Ph2 PCH2 N(CH3 )(CH2 )2 Ph, IrPNMPEA) and ruthenium(II) (Ru(η6 -p-cymene)Cl2 Ph2 PCH2 N(CH3 )(CH2 )2 Ph, RuPNMPEA) complexes. They were characterized using a vast array of methods, including 1D and 2D NMR, ESI(+)MS spectrometry, elemental analysis, cyclic voltammetry (CV), electron spectroscopy in the UV-Vis range (absorption, fluorescence) and density functional theory (DFT). The initial antimicrobial activity in vitro toward Gram-positive and Gram-negative bacterial strains was examined, indicating that both complexes are selective towards Gram-positive bacteria, e. g., Staphylococcus aureus, where the IrPNMPEA has been more bactericidal compared to RuPNMPEA. Additionally, the interactions of these compounds with various biomolecules, such as DNA (ctDNA, plasmid DNA, 9-ethylguanine (9-EtG), and 9-methyladenine (9-MeA)), nicotinamide adenine dinucleotide (NADH), glutathione (GSH), and ascorbic acid (Asc) were described. The results showed that both Ir(III) and Ru(II) complexes accelerate the oxidation process of NADH, GSH and Asc that appeared to occur by an electron transfer mechanism. Interestingly, only IrPNMPEA leads to the formation of various biomolecule adducts, which can explain its higher activity. Furthermore, RuPNMPEA and IrPNMPEA have been interacting with the DNA through weak noncovalent interactions.

Synthesis of 1,2,3-triazoles using Grignard reactions through the protection of azides.

An efficient method to prepare organomagnesium intermediates having a protected azido group is reported. Protection of azido groups with di-(tert-butyl)(4-(dimethylamino)phenylphosphine (amphos) and following iodine-magnesium exchange realized the preparation of organomagnesium intermediates, which served in the synthesis of diverse azides by transformation with various electrophiles followed by deprotection with elemental sulfur. Furthermore, click reactions of azides with alkynes enabled synthesizing a wide variety of 1,2,3-triazoles.

Atroposelective PIII /PV =O Redox Catalysis for the Isoquinoline-Forming Staudinger-aza-Wittig Reaction.

Herein, we describe the feasibility of atroposelective PIII /PV =O redox organocatalysis by the Staudinger-aza-Wittig reaction. The formation of isoquinoline heterocycles thereby enables the synthesis of a broad range of valuable atropisomers under mild conditions with enantioselectivities of up to 98 : 2 e.r. Readily prepared azido cinnamate substrates convert in high yield with stereocontrol by a chiral phosphine catalyst, which is regenerated using a silane reductant under Brønsted acid co-catalysis. The reaction provides access to diversified aryl isoquinolines, as well as benzoisoquinoline and naphthyridine atropisomers. The products are expeditiously transformed into N-oxides, naphthol and triaryl phosphine variants of prevalent catalysts and ligands. With dinitrogen release and aromatization as ideal driving forces, it is anticipated that atroposelective redox organocatalysis provides access to a multitude of aromatic heterocycles with precise control over their configuration.

Serinol-Based Versatile Disulfide-Reducing Reagent.

Here, we report the synthesis of disulfide-reducing agents 2-(dibenzylamino) propane-1,3-dithiol (DPDT) and 2-(dibenzylamino)-2-methylpropane-1,3-dithiol (DMPDT) from serinol and methyl serinol, respectively. DPDT was found to show greater stability than DMPDT. Hence, the effectiveness of DPDT as a reducing agent was evaluated in both liquid and solid phases. The reducing capacity of this agent was comparable to that of DTT.