P4 Activation Research Articles

Schrittweiser Abbau von weißem Phosphor: Experimentelle und computergestützte Studien zum Mechanismus der P4‐Hydrostannylierung

AbstractDie Hydrostannylierung der wichtigen Basischemikalie weißer Phosphor (P4) ermöglicht in einer Eintopf‐Reaktion und sogar auf katalytischem Weg die Synthese nützlicher P1‐Produkte. Bisher ist das mechanistische Verständnis dieser Methode jedoch mangelhaft, was die Nutzung für weitere Reaktionen einschränkt. Mit Hilfe von sterisch anspruchsvollen Zinnhydriden, zeitaufgelösten 31P‐NMR‐Experimenten und DFT‐Rechnungen geben wir nun fundierte Einblicke in den Mechanismus der P4‐Hydrostannylierung und beschreiben die Identifikation und Isolierung bisher unbekannter Reaktionsintermediate. Die Ergebnisse erlauben Rückschlüsse zur Kinetik der Reaktion und liefern praktische Hinweise für zukünftige Arbeiten auf dem Gebiet der P4‐Aktivierung.

Unravelling White Phosphorus: Experimental and Computational Studies Reveal the Mechanisms of P4 Hydrostannylation.

The hydrostannylation of white phosphorus (P4) allows this crucial industrial precursor to be easily transformed into useful P1 products via direct, 'one pot' (or even catalytic) procedures. However, a thorough mechanistic understanding of this transformation has remained elusive, hindering attempts to use this rare example of successful, direct P4 functionalization as a model for further reaction development. Here, we provide a deep and generalizable mechanistic picture for P4 hydrostannylation by combining DFT calculations with in situ 31P NMR reaction monitoring and kinetic trapping of previously unobservable reaction intermediates using bulky tin hydrides. The results offer important insights into both how this reaction proceeds and why it is successful and provide implicit guidelines for future research in the field of P4 activation.

Cooperative Rare-Earth/Lithium-Mediated Conversion of White Phosphorus.

The rare-earth/lithium cooperative effect on functionalization of white phosphorus has been investigated. The reaction of diazabutadiene-supported yttrium hydride chelated a LiPPh2 molecule (LY ⋅ THF)2 (μ-H)2 [μ-PPh2 (Li)] (1, L=N,N'-di(2,6-diisopropylphenyl)-1,4-diazabutadiene) with P4 gave two novel mixed Y/Li multinuclear polyphosphorus complexes (LY ⋅ THF)2 [cyclo-P3 ]Li(THF)3 (2) and [Li(THF)4 ]+ [(LY ⋅ THF)3 (norborane-P7 )Li(THF)]- (3), accompanied with the elimination of diphosphorus compound Ph2 PPPh2 (4) and H2 . However, the comparative reaction of yttrium hydride (LY ⋅ THF)2 (μ-H)2 with P4 afforded a trinuclear yttrium pyramid-P4 complex (LY ⋅ THF)3 (μ3 -P(PH)3 ) (5). Further investigations show that 5 cannot continuously react with LiPPh2 to form 2 and 3, and LiPPh2 reacted with P4 to form a Zintl-P7 lithium complex (TMEDA⋅Li)3 (Zintl-P7 ) (6) and 4. These results indicated that the cooperation of Y/Li for activation of P4 is a key for the formation of 2 and 3. All new compounds have been characterized by NMR spectroscopy and single-crystal X-ray diffraction studies.

PNP Ligands in Cobalt-Mediated Activation and Functionalization of White Phosphorus.

Transition-metal mediated white phosphorus activation is of high interest as an ecological alternative to P4 chlorination pathway to the practically useful phosphorus products. Herein, we report a facile approach for P4 activation, transformation and subsequent functionalization using cobalt complexes bearing PNP ligands. The use of N,N-bis(diphenylphosphino)amine as a ligand allows one to transform P4 tetrahedron into a zig-zag chain with the formation of complex [Co(Ph2 PNHP(Ph2 )PPPPP(Ph2 )NHPPh2 )]BF4 (4). The presence of organic substituent at nitrogen atom in PNP ligand enables one to obtain complexes with η1 -coordinated P4 molecule, which indicates a crucial role of N-H bond in transformation of white phosphorus tetrahedron. Additionally, complex 4 can readily be functionalized by means of the reaction with Ph2 PCl leading to the formation of a new complex bearing unique P9 -ligand. The obtained results provide opportunities for facile construction of new polyphosphorus ligands in the coordination sphere of transition metal complexes.

PNP Ligands in Cobalt‐Mediated Activation and Functionalization of White Phosphorus

AbstractTransition‐metal mediated white phosphorus activation is of high interest as an ecological alternative to P4 chlorination pathway to the practically useful phosphorus products. Herein, we report a facile approach for P4 activation, transformation and subsequent functionalization using cobalt complexes bearing PNP ligands. The use of N,N‐bis(diphenylphosphino)amine as a ligand allows one to transform P4 tetrahedron into a zig‐zag chain with the formation of complex [Co(Ph2PNHP(Ph2)PPPPP(Ph2)NHPPh2)]BF4 (4). The presence of organic substituent at nitrogen atom in PNP ligand enables one to obtain complexes with η1‐coordinated P4 molecule, which indicates a crucial role of N−H bond in transformation of white phosphorus tetrahedron. Additionally, complex 4 can readily be functionalized by means of the reaction with Ph2PCl leading to the formation of a new complex bearing unique P9‐ligand. The obtained results provide opportunities for facile construction of new polyphosphorus ligands in the coordination sphere of transition metal complexes.

Recent Breakthroughs in P4 Chemistry: Towards Practical, Direct Transformations into P1 Compounds

AbstractFor several decades, academic researchers have been intensively studying the chemistry of white phosphorus (P4) in the hope of developing direct methods for its transformation into useful P‐containing products. This would bypass the hazardous, multistep procedures currently relied on by industry. However, while academically interesting P4 activation reactions have become well established, their elaboration into useful, general synthetic procedures has remained out of reach. Very recently, however, a series of independent reports has begun to change this state of affairs. Each shows how relatively simple and practical synthetic methods can be used to access academically or industrially relevant P1 compounds from P4 directly, in “one pot” or even in a catalytic fashion. These reports mark a step change in the field of P4 chemistry, and suggest its possible transition from an area of largely academic interest to one with the promise of true synthetic relevance.

Recent Breakthroughs in P4 Chemistry: Towards Practical, Direct Transformations into P1 Compounds.

For several decades, academic researchers have been intensively studying the chemistry of white phosphorus (P4) in the hope of developing direct methods for its transformation into useful P‐containing products. This would bypass the hazardous, multistep procedures currently relied on by industry. However, while academically interesting P4 activation reactions have become well established, their elaboration into useful, general synthetic procedures has remained out of reach. Very recently, however, a series of independent reports has begun to change this state of affairs. Each shows how relatively simple and practical synthetic methods can be used to access academically or industrially relevant P1 compounds from P4 directly, in “one pot” or even in a catalytic fashion. These reports mark a step change in the field of P4 chemistry, and suggest its possible transition from an area of largely academic interest to one with the promise of true synthetic relevance.

Uranium(III)–Phosphorus(III) Synergistic Activation of White Phosphorus and Arsenic

Uranium(III)–Phosphorus(III) Synergistic Activation of White Phosphorus and Arsenic

D/f‐Polypnictides Derived by Non‐Classical Ln2+ Compounds: Synthesis, Small Molecule Activation and Optical Properties

Reduction chemistry induced by divalent lanthanides has been primarily focused on samarium so far. In light of the rich physical properties of the lanthanides, this limitation to one element is a drawback. Since molecular divalent compounds of almost all lanthanides have been available for some time, we used one known and two new non‐classical reducing agents of the early lanthanides to establish a sophisticated reduction chemistry. As a result, six new d/f‐polyphosphides or d/f‐polyarsenides, [K(18‐crown‐6)] [Cp′′2Ln(E5)FeCp*] (Ln=La, Ce, Nd; E=P, As) were obtained. Their reactivity was studied by activation of P4, resulting in a selective expansion of the P5 rings. The obtained compounds [K(18‐crown‐6)] [Cp′′2Ln(P7)FeCp*] (Ln=La, Nd) are the first examples of an activation of P4 by a f‐element‐polypnictide complex. Additionally, the first systematic femtosecond (fs)‐spectroscopy investigations of d/f‐polypnictides are presented to showcase the advantages of having access to a broader series of lanthanide compounds.

Transition-Metal-Mediated Functionalization of White Phosphorus.

Recently there has been great interest in the reactivity of transition‐metal (TM) centers towards white phosphorus (P4). This has ultimately been motivated by a desire to find TM‐mediated alternatives to the current industrial routes used to transform P4 into myriad useful P‐containing products, which are typically indirect, wasteful, and highly hazardous. Such a TM‐mediated process can be divided into two steps: activation of P4 to generate a polyphosphorus complex TM‐Pn, and subsequent functionalization of this complex to release the desired phosphorus‐containing product. The former step has by now become well established, allowing the isolation of many different TM‐Pn products. In contrast, productive functionalization of these complexes has proven extremely challenging and has been achieved only in a relative handful of cases. In this review we provide a comprehensive summary of successful TM‐Pn functionalization reactions, where TM‐Pn must be accessible by reaction of a TM precursor with P4. We hope that this will provide a useful resource for continuing efforts that are working towards this highly challenging goal of modern synthetic chemistry.

P4H]+[Al(OTeF5)4]-: protonation of white phosphorus with the Brønsted superacid H[Al(OTeF5)4](solv).

A sustainable transformation of white phosphorus (P4) into chemicals of higher value is one of the key aspects in modern phosphorus research. Even though the chemistry of P4 has been investigated for many decades, its chemical reactivity towards the simplest electrophile, the proton, is still virtually unknown. Based on quantum-chemical predictions, we report for the first time the successful protonation of P4 by the Brønsted acid H[Al(OTeF5)4](solv). Our spectroscopic results are in agreement with acid-mediated activation of P4 under protonation of an edge of the P4-tetrahedron and formation of a three-center two-electron P-H-P bond. These investigations are of fundamental interest as they permit the activation of P4 with the simplest electrophile as a new prototype reaction for this molecule.

Cross talk between progesterone receptors and retinoic acid receptors in regulation of cytokeratin 5-positive breast cancer cells.

Half of estrogen receptor-positive breast cancers contain a subpopulation of cytokeratin 5 (CK5)-expressing cells that are therapy resistant and exhibit increased cancer stem cell (CSC) properties. We and others have demonstrated that progesterone (P4) increases CK5+ breast cancer cells. We previously discovered that retinoids block P4 induction of CK5+ cells. Here we investigated the mechanisms by which progesterone receptors (PR) and retinoic acid receptors (RAR) regulate CK5 expression and breast CSC activity. After P4 treatment, sorted CK5+ compared to CK5- cells were more tumorigenic in vivo. In vitro, P4-treated breast cancer cells formed larger mammospheres and silencing of CK5 using small hairpin RNA abolished this P4-dependent increase in mammosphere size. Retinoic acid (RA) treatment blocked the P4 increase in CK5+ cells and prevented the P4 increase in mammosphere size. Dual small interfering RNA (siRNA) silencing of RARα and RARγ reversed RA blockade of P4-induced CK5. Using promoter deletion analysis, we identified a region 1.1 kb upstream of the CK5 transcriptional start site that is necessary for P4 activation and contains a putative progesterone response element (PRE). We confirmed by chromatin immunoprecipitation that P4 recruits PR to the CK5 promoter near the -1.1 kb essential PRE, and also to a proximal region near -130 bp that contains PRE half-sites and a RA response element (RARE). RA induced loss of PR binding only at the proximal site. Interestingly, RARα was recruited to the -1.1 kb PRE and the -130 bp PRE/RARE regions with P4, but not RA alone or RA plus P4. Treatment of breast cancer xenografts in vivo with the retinoid fenretinide reduced the accumulation of CK5+ cells during estrogen depletion. This reduction, together with the inhibition of CK5+ cell expansion through RAR/PR cross talk, may explain the efficacy of retinoids in prevention of some breast cancer recurrences.

Nacnac-Cobalt-Mediated P4 Transformations.

A comparison of P4 activations mediated by low‐valent β‐diketiminato (L) cobalt complexes is presented. The formal Co0 source [K2(L3Co)2(μ2:η1,η1‐N2)] (1) reacts with P4 to form a mixture of the monoanionic complexes [K(thf)6][(L3Co)2(μ2:η4,η4‐P4)] (2) and [K(thf)6][(L3Co)2(μ2:η3,η3‐P3)] (3). The analogue CoI precursor [L3Co(tol)] (4 a), however, selectively yields the corresponding neutral derivative [(L3Co)2(μ2:η4,η4‐P4)] (5 a). Compound 5 a undergoes thermal P atom loss to form the unprecedented complex [(L3Co)2(μ2:η3,η3‐P3)] (6). The products 2 and 3 can be obtained selectively by an one‐electron reduction of their neutral precursors 5 a and 6, respectively. The electrochemical behaviour of 2, 3, 5 a, and 6 is monitored by cyclic voltammetry and their magnetism is examined by SQUID measurements and the Evans method. The initial CoI‐mediated P4 activation is not influenced by applying the structurally different ligands L1 and L2, which is proven by the formation of the isostructural products [(LCo)2(μ2:η4,η4‐P4)] [L=L3 (5 a), L1 (5 b), L2 (5 c)].

The Cobalt cyclo-P4 Sandwich Complex and Its Role in the Formation of Polyphosphorus Compounds.

A synthetic approach to the sandwich complex [Cp′′′Co(η4‐P4)] (2) containing a cyclo‐P4 ligand as an end‐deck was developed. Complex 2 is the missing homologue in the series of first‐row cyclo‐Pn sandwich complexes, and shows a unique tendency to dimerize in solution to form two isomeric P8 complexes [(Cp′′′Co)2(μ,η4:η2:η1‐P8)] (3 and 4). Reactivity studies indicate that 2 and 3 react with further [Cp′′′Co] fragments to give [(Cp′′′Co)2(μ,η2:η2‐P2)2] (5) and [(Cp′′′Co)3P8] (6), respectively. Furthermore, complexes 2, 3, and 4 thermally decompose forming 5, 6, and the P12 complex [(Cp′′′Co)3P12] (7). DFT calculations on the P4 activation process suggest a η3‐P4 Co complex as the key intermediate in the synthesis of 2 as well as in the formation of larger polyphosphorus complexes via a unique oligomerization pathway.

Direct Synthesis of Phospholyl Lithium from White Phosphorus.

The selective construction of P-C bonds directly from P4 and nucleophiles is an ideal and step-economical approach to utilizing elemental P4 for the straightforward synthesis of organophosphorus compounds. In this work, a highly efficient one-pot reaction between P4 and 1,4-dilithio-1,3-butadienes was realized, which quantitatively affords phospholyl lithium derivatives. DFT calculations indicate that the mechanism is significantly different from that of the well-known stepwise cleavage of P-P bond in P4 activation. Instead, a cooperative nucleophilic attack of two Csp2 Li bonds on P4 , leading to simultaneous cleavage of two P-P bonds, is favorable. This mechanistic information offers a new view on the mechanism of P4 activation, as well as a reasonable explanation for the excellent yields and selectivity. This method could prove to be a useful route to P4 activation and the subsequent production of organophosphorus compounds.

Direct Synthesis of Phospholyl Lithium from White Phosphorus

AbstractThe selective construction of P−C bonds directly from P4 and nucleophiles is an ideal and step‐economical approach to utilizing elemental P4 for the straightforward synthesis of organophosphorus compounds. In this work, a highly efficient one‐pot reaction between P4 and 1,4‐dilithio‐1,3‐butadienes was realized, which quantitatively affords phospholyl lithium derivatives. DFT calculations indicate that the mechanism is significantly different from that of the well‐known stepwise cleavage of P−P bond in P4 activation. Instead, a cooperative nucleophilic attack of two C Li bonds on P4, leading to simultaneous cleavage of two P−P bonds, is favorable. This mechanistic information offers a new view on the mechanism of P4 activation, as well as a reasonable explanation for the excellent yields and selectivity. This method could prove to be a useful route to P4 activation and the subsequent production of organophosphorus compounds.

Formation of the spirocyclic, Si-centered cage cations [ClP(NSiMe3)2Si(NSiMe3)2P5](+) and [P5(NSiMe3)2Si(NSiMe3)2P5](2).

On account of our interest in P4 activation by phosphenium ion insertion into P-P bonds we have developed synthetic routes to bicyclic N-P-Si-heterocycle 7 and probed its reactivity towards GaCl3 and P4. A GaCl3-induced rearrangement of 7 leads to the in situ formation of spirocyclic, Si-centered phosphenium ions. Their insertion into P-P bonds of one or two P4 tetrahedra yields polyphosphorus cages [ClP(NSiMe3)2Si(NSiMe3)2P5](+) (19(+)) and [P5(NSiMe3)2Si(NSiMe3)2P5](2+) (13(2+)).

Selective functionalization of P₄ by metal-mediated C-P bond formation.

A new and selective one-step synthesis was developed for the first activation stage of white phosphorus by organic radicals. The reactions of NaCp(R) with P4 in the presence of CuX or FeBr3 leads to the clean formation of organic substituted P4 butterfly compounds Cp(R)2P4 (Cp(R): Cp(BIG)=C5(4-nBuC6H4)5 (1 a), Cp'''=C5H2tBu3 (1 b), Cp*=C5Me5 (1 c) und Cp(4iPr)=C5HiPr4 (1 d)). The reaction proceeds via the activation of P4 by Cp(R) radicals mediated by transition metals. The newly formed organic derivatives of P4 have been comprehensively characterized by NMR spectroscopy and X-ray crystallography.

Non-canonical progesterone signaling in granulosa cell function

It has been known for over 3 decades that progesterone (P4) suppresses follicle growth. It has been assumed that P4 acts directly on granulosa cells of developing follicles to slow their development, as P4 inhibits both mitosis and apoptosis of cultured granulosa cells. However, granulosa cells of developing follicles of mice, rats, monkeys, and humans do not express the A or B isoform of the classic nuclear receptor for P4 (PGR). By contrast, these granulosa cells express other P4 binding proteins, one of which is referred to as PGR membrane component 1 (PGRMC1). PGRMC1 specifically binds P4 with high affinity and mediates P4's anti-mitotic and anti-apoptotic action as evidenced by the lack of these P4-dependent effects in PGRMC1-depleted cells. In addition, mice in which PGRMC1 is conditionally depleted in granulosa cells show diminished follicle development. While the mechanism through which P4 activation of PGRMC1 affects granulosa cell function is not well defined, it appears that PGRMC1 controls granulosa cell function in part by regulating gene expression in T-cell-specific transcription factor/lymphoid enhancer factor-dependent manner. Clinically, altered PGRMC1 expression has been correlated with premature ovarian failure/insufficiency, polycystic ovarian syndrome, and infertility. These collective studies provide strong evidence that PGRMC1 functions as a receptor for P4 in granulosa cells and that altered expression results in compromised reproductive capacity. Ongoing studies seek to define the components of the signal transduction cascade through which P4 activation of PGRMC1 results in the regulation of granulosa cell function.

An Actinide Zintl Cluster: A Tris(triamidouranium)μ3‐η2:η2:η2‐Heptaphosphanortricyclane and Its Diverse Synthetic Utility

An Actinide Zintl Cluster: A Tris(triamidouranium)μ₃‐η²:η²:η²‐Heptaphosphanortricyclane and Its Diverse Synthetic Utility