Phosphorus Heterocycles Research Articles

Palladium-Catalyzed C-H Functionalization and Flame-Retardant Properties of Isophosphinolines.

C-H activation is a powerful strategy for forming C-C bonds without the need for prefunctionalization. In this paper, we present a general, direct, and regioselective palladium-catalyzed functionalization of a phosphorus heterocycle, 2-phenyl-1H-isophosphinoline 2-oxide. The mild reaction conditions enabled the introduction of various functionalized alkenes. Moreover, the flame-retardant properties of selected products clearly highlighted the synergy between the phosphine oxide and another heteroatom-based group, even in the condensed phase.

Cycloadditions of Diazoalkenes with P4 and tBuCP: Access to Diazaphospholes.

Diazoalkenes readily react with tert-butylphosphaalkyne (tBuCP) and white phosphorus (P4) to afford novel phosphorus heterocycles, 3H-1,2,4-diazamonophospholes and 1,2,3,4-diazadiphospholes. Both species represent rare examples of neutral heterophospholes. The mechanism of formation and the electronic structures of these formal (3+2) cycloaddition products were analyzed computationally. The new phospholes form structurally diverse coordination compounds with transition metal and main group elements. Given the growing number of stable diazoalkenes, this work offers a straightforward route to neutral aza(di-)phospholes as a new ligand class.

Cycloadditionen von Diazoalkenen mit P4 und tBuCP: Ein Zugang zu Diazaphospholen

AbstractReaktionen von Diazoalkenen mit tert‐Butylphosphaalkin (tBuCP) und weißem Phosphor (P4) führen zu neuen Phosphorheterocyclen, 3H‐1,2,4‐Diazamonophospholen und 1,2,3,4‐Diazadiphospholen. Die erhaltenen Verbindungen sind seltene Beispiele für neutrale Heterophosphole. Der Bildungsmechanismus der formalen (3+2)‐Cycloadditionsprodukte wurde quantenchemisch berechnet und die elektronischen Strukturen analysiert. Die neuen Phosphole bilden strukturell vielfältige Koordinationsverbindungen mit Übergangsmetallen und Hauptgruppenelementen. Angesichts der wachsenden Anzahl stabiler Diazoalkene bietet diese Arbeit einen unmittelbaren Zugang zu neutralen Aza(di‐)phospholen als neue Ligandenklasse.

Advancement in Synthetic Strategies of Phosphorus Heterocycles: Recent Progress from Synthesis to Emerging Class of Optoelectronic Materials.

Organophosphorus heterocycles have long been acknowledged for their significant potential across diverse fields, including catalysis, material science, and drug development. Incorporating phosphorus functionalities into organic compounds offers a means to effectively tailor their medicinal properties, augment biological responses, and enhance selectivity and bioavailability. The distinctive physical and photoelectric characteristics of phosphorus-containing conjugated compounds have garnered considerable interest as promising materials for organic optoelectronics. These compounds find extensive utility in various applications such as light-emitting diodes, photovoltaic cells, phosphole-based fluorophores, and semiconductors.

Low-Valent Transition Metalate Anions in Synthesis, Small Molecule Activation, and Catalysis.

This review surveys the synthesis and reactivity of low-oxidation state metalate anions of the d-block elements, with an emphasis on contributions reported between 2006 and 2022. Although the field has a long and rich history, the chemistry of transition metalate anions has been greatly enhanced in the last 15 years by the application of advanced concepts in complex synthesis and ligand design. In recent years, the potential of highly reactive metalate complexes in the fields of small molecule activation and homogeneous catalysis has become increasingly evident. Consequently, exciting applications in small molecule activation have been developed, including in catalytic transformations. This article intends to guide the reader through the fascinating world of low-valent transition metalates. The first part of the review describes the synthesis and reactivity of d-block metalates stabilized by an assortment of ligand frameworks, including carbonyls, isocyanides, alkenes and polyarenes, phosphines and phosphorus heterocycles, amides, and redox-active nitrogen-based ligands. Thereby, the reader will be familiarized with the impact of different ligand types on the physical and chemical properties of metalates. In addition, ion-pairing interactions and metal-metal bonding may have a dramatic influence on metalate structures and reactivities. The complex ramifications of these effects are examined in a separate section. The second part of the review is devoted to the reactivity of the metalates toward small inorganic molecules such as H2, N2, CO, CO2, P4 and related species. It is shown that the use of highly electron-rich and reactive metalates in small molecule activation translates into impressive catalytic properties in the hydrogenation of organic molecules and the reduction of N2, CO, and CO2. The results discussed in this review illustrate that the potential of transition metalate anions is increasingly being tapped for challenging catalytic processes with relevance to organic synthesis and energy conversion. Therefore, it is hoped that this review will serve as a useful resource to inspire further developments in this dynamic research field.

Highly selective, reversible water activation by P,N-cooperativity in pyridyl-functionalized phosphinines.

Tetrapyridyl-functionalized phosphinines were prepared and structurally characterized. The donor-functionalized aromatic phosphorus heterocycles react highly selectively and even reversibly with water. Calculations reveal P,N-cooperativity for this process, with the flanking pyridyl groups serving to kinetically enhance the formal oxidative addition process of H2O to the low-coordinate phosphorus atom via H-bonding. Subsequent tautomerization forms 1,2-dihydrophosphinine derivatives, which can be quantitatively converted back to the phosphinine by applying vacuum, even at room temperature. This process can be repeated numerous times, without any sign of decomposition of the phosphinine. In the presence of CuI·SMe2, dimeric species of the type ([Cu2I2(phosphinine)]2) are formed, in which each phosphorus atom shows the less common μ2-bridging 2e--lone-pair-donation to two Cu(i)-centres. Our results demonstrate that fully unsaturated phosphorus heterocycles, containing reactive P[double bond, length as m-dash]C double bonds, are interesting candidates for the activation of E-H bonds, while the aromaticity of such compounds plays an appreciable role in the reversibility of the reaction, supported by NICS calculations.

Transition-Metal-Free Electrochemical Selenylative Cyclization of Alkynyl Phosphonates.

Unprecedented regioselective electrochemical tandem selenation/cyclization of alkynyl phosphonates with diselenide is described here. These obtained selenoether products can be chemo-selectively converted into halogen-functionalized cyclic enol phosphonates under our electrochemical conditions. These protocols provide straightforward access to valuable cyclic enol phosphonate or phosphaisocoumarins under the electrochemical and transition-metal-free conditions. The robustness of these transformations was illustrated by their compatibility with various complex natural products and bioactive molecules. The selenoether and halogen functional groups allow the further diversification of the phosphorus heterocycles thus obtained.

Synthesis and Chemistry of 1,2,4,3-Triazaphosphole Derivatives

Abstract: This review describes the progress made during the last fifty years in the synthesis and chemistry of 1,2,4,3 triazaphospholes. This class of compounds has attracted tremendous homogeneous catalysis and interest in molecular materials science. These fascinating phosphorus heterocycles have conjugated π systems with high degrees of aromaticity. 1,2,4,3- Triazaphospholes can be designed through [3+2] cyclocondensation between functionalized hydrazines with phosphonoimidates that allow the incorporation of additional donor substituents into specific positions of the phosphorus heterocycle. In addition, [4+1] cyclocondensation between functionalized amidrazones and active phosphorus reagents is the most synthetically accessible method. The used strategies facilitated synthetic access to a completely new set of triazaphospholes leading to a much broader scope for potential applications. 1,2,4,3-triazaphospholes displayed reactivity towards a variety of reagents. The phosphorus is particularly prone to undergo oxidative 1,1-addition. Protic reagents such as alcohols, phenols, and amines can be added across the P=N bond of 2H-1,2,4,3-triazaphospholes to yield the dihydro-1,2,4,3-triazaphosphole derivatives. 1H- and 2H-1,2,4,3- triazaphospholes reacted with alcohols, ammonia and amines in the presence of sulfur or selenium to form dihydro- 1,2,4,3-triazaphosphole 3-chalcogenides. The appropriate difunctional reagents such as glycols, 2-azido alcohols and phenol with a heterodiene function in the ortho position reacted with 2H-1,2,4,3-triazaphospholes to yield products formed via 1,2-addition on P=N bond. Similar behavior is shown by 2-hydroxyacetophenone and 2- hydroxy-benzophenone. 2H-1,2,4,3-Triazaphospholes reacted with acetylenes to form [3+2] cycloadducts; the latter change to 1,2,3-diazaphospholes. [4+1] Cycloadditions occurred with α-diimines, azodicarboxylic esters, and 1,2-diketones; in the latter two cases, the resulting products dimerize.

Boundaries of the Hyperconjugation from π-Extended Six-Membered Phosphorus Heterocycles.

In the context of materials science, six-membered phosphorus heterocycles are intriguing building blocks due to their tunable properties through phosphorus post-functionalization and their unique hyperconjugative effects arising from the phosphorus substituents that contribute to further tuning the optoelectronic properties of the system. Seeking for the discovery of improved materials, the latter features have triggered an astonishing evolution of molecular architectures based on phosphorus heterocycles. Theoretical calculations showed that the hyperconjugation causes a reduction in the S0-S1 gap, which strongly depends on the nature of both the P-substituent and the π-conjugated core, but where are the limits? Outlining the hyperconjugative effects of six-membered phosphorus heterocycles would allow scientists to know how to design next-generation organophosphorus systems with enhanced properties. Herein, we discovered that, in cationic six-membered phosphorus heterocycles, an increase in the hyperconjugation does not affect the S0-S1 gap anymore; i.e., quaternizing the phosphorus atoms leads to properties that go beyond those provoked by hyperconjugative effects. DFT calculations revealed that the latter is particularly marked in phosphaspiro derivatives. Our detailed investigations spotlight the potential of π-extended systems based on six-membered phosphorus spiroheterocycles for accessing properties beyond those achieved to date through hyperconjugative effects, thus laying the groundwork for new research possibilities toward improved organophosphorus systems.

Synthesis and Unexpected Optical Properties of Ionic Phosphorus Heterocycles with P-Regulated Noncovalent Interactions.

Optoelectronic properties of organic chromophores (OCPs) are to a large extent dictated by the chemical structures. Herein, we synthesized a new series of ionic phosphorus(P)-heteropines via the methylation of the P(III) center. Our studies revealed that methylation is highly dependent on the P(III) environments (NPN, NPC, and CPC), in which adjacent nitrogen atoms greatly withdraw electron density of the P(III) center. The observation of noncovalent interactions between solvent molecules and the molecular backbones of the related P-heterocycle in the single crystal structure implied tunable molecular conformations. Different from the red-shifted absorption and emission spectra of ionic P-OCPs induced by either decreased lowest unoccupied molecular orbital (LUMO) or intramolecular charge transfer (ICT) state in previous studies, current ionic P-heterocycles exhibit blue-shifted absorption and emission spectra compared to the nonionic counterparts. Our experimental and theoretical studies suggest that the unexpected photophysical characters are probably due to the counter-anion induced structure twisting via intermolecular noncovalent interactions between NH-indole and O(OTf), and/or strong intermolecular O···F bonding between O(MI) and F(OTf). Our studies also revealed that the P-environments (NPN, NPC, and CPC) conjunctly impact the photophysical properties of the ionic P-heteropines. Overall, the fact that the P-environment-regulated noncovalent interactions induce the rich structure dynamics and photophysics offers us with a new and effective strategy to fine-tune the optical properties of OCPs.

Fe3O4 nanoparticles as an efficient catalyst for one-pot synthesis of novel fused phosphorus heterocycles bearing diethyl phosphonate

An efficient and practical method for the synthesis of novel fused phosphorus heterocycles incorporating diethyl phosphonate by the one-pot in the presence of Fe3O4 nanoparticles as a reusable catalyst was achieved. The four-component reactions of ortho-substituted anilines, namely 2-aminophenol, 2-aminothiophenol and 1,2-phenylenediamine with salicylaldehyde, diethyl phosphite and hexaethylphosphorus triamide in the presence of Fe3O4 nanoparticles as a catalyst at 80–90 °C afforded the corresponding 1,3,2-benzo(oxaza/thiaza/diaza)phospholo[2,3-b][1,3,2]benzoxazaphosphinines 1–3 in good yields (80-84%). When the same reactions were repeated by substitution of salicylaldehyde with benzaldehyde, the 1,2-benzazaphospholo[2,1-b][1,3,2]benzo(oxaza/thiaza)phospholes 4 and 5 and 1,3,2-benzodiazaphosphole 6 derivatives were isolated in 78–83% yields. The structures of the synthesized compounds were established by elemental analysis and spectroscopic techniques (IR, MS and NMR).

Improving the accuracy of 31P NMR chemical shift calculations by use of scaling methods.

Calculation of 31P NMR chemical shifts for a series of tri- and tetracoordinate phosphorus compounds using several basis sets and density functional theory (DFT) functionals gave a modest fit to experimental chemical shifts, but an excellent linear fit when plotted against the experimental values. The resultant scaling methods were then applied to a variety of "large" compounds previously selected by Latypov et al. and a set of stereoisomeric and unusual compounds selected here. No one method was best for all structural types. For compounds that contain P-P bonds and P-C multiple bonds, the Latypov et al. method using the PBE0 functional was best (mean absolute deviation/root mean square deviation (MAD/RMSD) = 6.9/8.5 ppm and 6.6/8.2 ppm, respectively), but for the full set of compounds gave higher deviations (MAD/RMSD = 8.2/12.3 ppm), and failed by over 60 ppm for a three-membered phosphorus heterocycle. Use of the M06-2X functional for both the structural optimization and NMR chemical shift calculation was best overall for the compounds without P-C multiple bonds (MAD/RMSD = 5.4/7.1 ppm), but failed by 30-49 ppm for compounds having any P-C multiple-bond character. Failures of these magnitudes have not been reported previously for these widely used functionals. These failures were then used to screen a variety of recommended functionals, leading to better overall methods for calculation of these chemical shifts: optimization with the M06-2X functional and NMR calculation with the PBE0 or ωB97x-D functionals gave values for MAD/RMSD = 6.9/8.5 ppm and 6.8/9.1 ppm, respectively, over an experimental chemical shift range of -181 to 356 ppm. Due to the unexplained failures observed, we recommend use of more than one method when looking at novel structures.

Copper(I) and Gold(I) Complexes of Aminofunctionalized Phosphinines: Synthesis and Structural Characterization

AbstractA series of novel 3‐N,N‐dimethylaminofunctionalized phosphinines were synthesized and structurally characterized. DFT calculations showed that these aromatic phosphorus heterocycles possess stronger π‐donor and σ‐donor properties compared to the parent phosphinine C5H5P. With CuBr ⋅ SMe2, the corresponding complexes of the type [(phosphinine)2CuBr]2are formed, which show the classical terminal σ‐coordination mode of the phosphorus donor towards the Cu(I) center. Upon reaction with AuCl ⋅ SMe2, mononuclear phosphinine‐Au(I)Cl complexes could be obtained and crystallographically characterized. Moreover, the presence of a SiMe3‐group and a donor‐functionality provide the possibility for post‐synthetic ligand modifications. With CuCl ⋅ SMe2the phosphinine‐based hydrochloride salts forms a rare Cu(I) complex with a Cu4Cl4‐core, that contains two pairs of differently coordinating phosphinine ligands.

Phospholenes from Phosphabenzenes by Selective Ring Contraction.

A 3-amino-functionalized phosphabenzene (phosphinine) has been synthesized and structurally characterized. The pyramidalized nitrogen atom of the dimethylamino substituent indicates only a weak interaction between the lone pair of the nitrogen atom and the aromatic phosphorus heterocycle, resulting in somewhat basic character. It turned out that the amino group can indeed be protonated by HCl. In contrast to pyridines, however, the phosphabenzene-ammonium salt undergoes a selective ring contraction to form a hydroxylphospholene oxide in the presence of additional water. Based on deuterium labeling experiments and quantum chemical calculations, a rational mechanism for this hitherto unknown conversion is proposed.

Phosphinine Selenide: Noncovalent Interactions with Organoiodines and Elemental Iodine, and Reactivity towards Potassium Cyanide.

A co-crystalline adduct consisting of a phosphinine selenide and an organohalide was obtained by slow evaporation of the solvent from a mixture of 2,6-bis(trimethylsilyl)phosphinine selenide and 1,4-diiodotetrafluorobenzene (1,4-TFDIB). The crystallographic characterization of the product shows π-π stacking, F⋅⋅⋅H hydrogen bonding between 1,4-TFDIB and the phosphinine selenide, as well as F⋅⋅⋅F interactions between 1,4-TFDIB molecules. Moreover, the phosphorus heterocycle could be crystallized with diiodine to form a 1 : 1 adduct. The d(I-I) distance in this compound is 2.8475(3) Å, which is shorter than the corresponding one in triphenylphosphine selenide diiodide, reflecting the weaker net-donor power of the phosphinine selenide towards diiodine. The phosphinine selenide could also be used as a selenium transfer reagent to generate KSeCN from KCN.

Muon Spin Rotation/Resonance (μSR) for Studying Radical Reactivity of Unsaturated Organophosphorus Compounds.

The positive muon (μ+ ) can be regarded as a light isotope of proton and has been an important tool to study radical reactions of organic compounds. Recently, muons have been applied to produce short-lived paramagnetic species from the heavier unsaturated organic molecules including the p-block elements. This article overviews recent muon spin rotation/resonance (μSR) studies on the phosphorus analogs of alkenes, anthracenes, and cyclobutane-1,3-diyls together with the fundamentals of μSR. The acyclic phosphaalkene of P=C and phosphasilenes of P=Si can accept muonium (Mu=[μ+ e- ]) at the heavier double bonds, and the corresponding radicals have been characterized. The phosphorus atom in 9-phosphaanthracene, whose P=C double bond is stabilized by the peri-substituted CF3 groups, predominantly captures muonium to provide the corresponding paramagnetic fused heterocyclic system. The peri-trifluoromethyl groups are functional to promote the unprecedented light isotope effect of muon providing the planar three-cyclic molecular structure to consume the increased zero-point energy. The formally open-shell singlet 1,3-diphosphacyclobutane-2,4-diyl unit can accept muonium at the (ylidic) phosphorus or the skeletal radicalic carbon, and the corresponding paramagnetic phosphorus heterocycles can be characterized by μSR. The findings on these muoniation processes to the unsaturated phosphorus-containing compounds will contribute not only to development of novel paramagnetic functional species but also to progress on muon science.

Luminescent Pyrrole-Based Phosphaphenalene Gold Complexes: Versatile Anticancer Tools with Wide Applicability.

Brain cancer, one of the most lethal diseases, urgently requires the discovery of novel theranostic agents. In this context, molecules based on six‐membered phosphorus heterocycles – phosphaphenalenes – are especially attractive; they possess unique characteristics that allow precise chemical engineering. Herein, we demonstrate that subtle structural modifications of the phosphaphenalene‐based gold(I) complexes lead to modify their electronic distribution, endow them with marked photophysical properties and enhance their efficacy against cancer. In particular, phosphaphenalene‐based gold(I) complexes containing a pyrrole ring show antiproliferative properties in 14 cell lines including glioblastomas, brain metastases, meningiomas, IDH‐mutant gliomas and head and neck cancers, reaching IC50 values as low as 0.73 μM. The bioactivity of this new family of drugs in combination with their photophysical properties thus offer new research possibilities for both the fundamental investigation and treatment of brain cancer.

Copper‐Catalyzed Dynamic Kinetic C−P Cross‐Coupling/Cyclization for the Concise Asymmetric Synthesis of Six‐, Seven‐ and Eight‐MemberedP‐Stereogenic Phosphorus Heterocycles

AbstractA copper‐catalyzed asymmetric aryl C−P cross‐coupling/cyclization reaction was successfully developed via dynamic kinetic asymmetric transformation (DYKAT) under mild conditions. This study provides a general and simple method for the catalytic enantioselective synthesis of stable six‐, seven‐ and eight‐membered P‐stereogenic phosphorus heterocycles with excellent enantioselectivities and moderate to high yields. One‐pot gram‐scale asymmetric synthesis of the P‐stereogenic P‐heterocycle from commercially available materials was also successfully accomplished with excellent enantioselectivity and high yield.

Copper-Catalyzed Dynamic Kinetic C-P Cross-Coupling/Cyclization for the Concise Asymmetric Synthesis of Six-, Seven- and Eight-Membered P-Stereogenic Phosphorus Heterocycles.

A copper-catalyzed asymmetric aryl C-P cross-coupling/cyclization reaction was successfully developed via dynamic kinetic asymmetric transformation (DYKAT) under mild conditions. This study provides a general and simple method for the catalytic enantioselective synthesis of stable six-, seven- and eight-membered P-stereogenic phosphorus heterocycles with excellent enantioselectivities and moderate to high yields. One-pot gram-scale asymmetric synthesis of the P-stereogenic P-heterocycle from commercially available materials was also successfully accomplished with excellent enantioselectivity and high yield.

Cover Feature: Borane Adducts of Aromatic Phosphorus Heterocycles: Synthesis, Crystallographic Characterization and Reactivity of a Phosphinine‐B(C6F5)3 Lewis Pair (Chem. Eur. J. 7/2022)

The first crystallographically characterized phosphinine–borane adduct mimics frustrated Lewis-pair reactivity. In the presence of alkynes, alkenes and esters, a facile conversion to novel phosphinine-based species is achieved even at room temperature. Our results provide fascinating new perspectives for the future, particularly with respect to the activation of small molecules. More information can be found in the Research Article by T. Böttcher, C. Müller et al. (DOI: 10.1002/chem.202104135).