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The reaction of 1,3,5-(iPr2PO)3C6H3 with Co2(CO)8 leads to the isolation of a POCOP-type mononuclear pincer complex {κP,κC,κP-2,4,6-(iPr2PO)3C6H2}Co(CO)2 (1) or a tetranuclear species {κP-{κP,κC,κP-2,4,6-(iPr2PO)3C6H2}Co(CO)2}2Co2(CO)6 (2), depending on the ligand to cobalt ratio employed. The latter compound can be an impurity during the synthesis of {2,6-(iPr2PO)2-4-Me2N-C6H2}Co(CO)2, when the ligand precursor 5-(dimethylamino)resorcinol is contaminated with phloroglucinol due to incomplete monoamination. Similarly, the reaction of 1,3,5-(iPr2PO)3C6H3 with NiCl2 in the presence of 4-dimethylaminopyridine provides {κP,κC,κP-2,4,6-(iPr2PO)3C6H2}NiCl (3) bearing an appended phosphinite group. Structures 1–3 have been studied by X-ray crystallography.

Hydroboration of carbon dioxide (CO2) catalysed by bis(phosphinite) (POCOP) pincer nickel complexes is among the most efficient homogeneous processes for the reduction of CO2 to the methanol level. Although both POCOP pincer nickel hydride and thiolate complexes are effective catalysts, the latter is far more effective under the same conditions. The mechanism for nickel hydride complexes catalysed reactions is well-established. However, that for nickel thiolate complex catalysed reactions remains elusive. In this work, the mechanism for the reduction of CO2 catalysed by POCOP pincer nickel thiolate complexes was investigated using density functional theory. The calculated results indicated that the reaction occurs via a concerted catalytic process involving two active species and the hydride is transferred by a shuttle species. Specifically, the reaction proceeds through four cycles: formation of two active species (cycle I) followed by further reaction of these two species to form a hydride transfer shuttle which is responsible for hydride transfers CO2→HCOOBcat (cycle II), HCOOBcat→CH2O (cycle III) and CH2O→catBOCH3 (cycle IV). The calculated mechanism is in good agreement with the experimental observation that the reaction is exothermic with simultaneous HBcat degradation.

The synthesis of some “reverse pyridine” bis(phosphinite) pincer complexes of nickel and rhodium is reported. N-Functionalization of a POCOP ligand with a borane Lewis acid was found to permit cyclometalation with metal precursors, which reacted with the free base ligand in an undesired manner. Convenient removal of the coordinated Lewis acid was accomplished using polymer-supported 4-dimethylaminopyridine. The effects of borane Lewis acid coordination on the physical and spectroscopic properties of the pincer complexes were also assessed.

A new alkylation protocol for the synthesis of tertiary phosphonite­/phosphinite-boranes is developed. P-Alkylation products are obtained exclusively in moderate to very good yields from easily accessible (1-hydroxy-1-methylethyl)/(1-hydroxy-1-cyclohexyl) phosphonite/phosphinite-boranes upon reaction with a variety of electrophiles under mild conditions. The methodology opens up new synthetic routes for organophosphorus chemistry and offers access to valuable alkyl phosphonite/phosphinite-boranes. In contrast to previously reported oxidative removal–substitution sequences for the preparation of optically active phosphinite-boranes, our protocol provides a one-step procedure that occurs without loss of stereochemical information at phosphorus. This new approach provides a rather advantageous protocol when compared to direct alkylation methods (which may undergo P-epimerization) and occurs in a stereoselective manner even at 0 °C.

Lung cancer is one of the major causes of cancer-related deaths in the world. Non-small-cell lung cancer (NSCLC) is the most common type of lung cancer, and small-cell lung cancer (SCLC) is the most aggressive subtype of lung cancer. Proper therapies for SCLC have not yet been developed. However, new molecules have been designed and big innovation in treating SCLC has been achieved. Platinum-based antitumor drugs like cisplatin and carboplatin have several disadvantages including side effects, cisplatin-resistant tumors and limited solubility in aqueous media. Thus, two novel chiral aminoalcohol-based bis(phosphinite) ligands containing (η6-p-cymene)-Ru(II)-phosphinite and bis(phosphinite)–Pd(II) complexes were synthesized and evaluated for anticancer activity. In this study, the results showed that complex 1 has the strongest cytotoxic effects on SCLC and NSCLC cell lines. On the other hand, cisplatin, ruthenium and palladium complexes are capable to induce apoptosis. Especially, complexes 1 and 2 can induce apoptosis for both SCLC and NSCLC. When compared to the qRT-PCR and TUNEL results, we obtained a significant correlation between apoptotic index and p21, Bax gene expressions. This work revealed the potential of the synthesized complexes as anticancer agents with cytotoxic and pro-apoptotic activity as leading compounds for further anticancer researches. © 2020, Institute of Chemistry, Slovak Academy of Sciences.

A novel cobalt system featuring a Co–P moiety has been synthesized to study its metal–ligand cooperativity. A reversible conversion of a phosphide group to a P–P bond found in a dimeric cobalt(I) complex involves electron transfer between Co and P, in which a single electron transfer is successfully coupled with a redox change in each cobalt ion. Upon coordination of a π-acidic ligand such as acetonitrile and isocyanide at the cobalt site, the transformation of a dimeric to a monomeric cobalt complex occurs, which involves the migration of a phenolate group. During the conversion, a P–P bond was cleaved and converted to phosphide and phosphinite. Current Co–P metal–ligand cooperativity presented in this work has been explored structurally, spectroscopically and theoretically.

İyonik bir sıvıyı (IL) tanımlayan ilk çalışma 1914 yılında, etilamonyum nitratın ([EtNH3][NO3]; mp 13–14 °C) belirli fiziksel özelliklerini gözlemleyen Paul Walden tarafından yapılmıştır. Yeni bir malzeme sınıfının keşfi, o zamanlar fazla ilgi çekmese de bugün bu çalışma genellikle iyonik sıvılar alanının başlangıç noktası olarak kabul edilmektedir. İyonik sıvılar çevreye zarar vermeyen kimyasal ve fiziksel özelliklere sahip olmaları ve özellikle yapısal ayarlanabilirliklerinden dolayı organik sentezde katalizör veya reaksiyon ortamı olarak yaygın bir şekilde kullanılmaktadır. Bu çalışmada, iyonik sıvı bileşikleri olan 3-(3-kloro-2-hidroksipropil)-1-vinil-1H-imidazol-3-ium klorid (1) ve 3-(3-kloro-2-hidroksipropil)-1-bütil-1H-imidazol-3-ium klorid (2) literatüre uygun şekilde sentezlendi. Sentezlenen imidazol türevi iyonik sıvılar Schlenk-line tekniği kullanılarak -78 °C'de PPh2Cl veya PCy2Cl ile tepkimeye sokularak fosfinit ligandları 3, 4 ve 5 sentezlendi. Ligandlar kararsız olduğundan karakterizasyon işlemleri yapılamadı. Daha sonra bu fosfinit ligandlarının Ru (II) Ir (III) ve Rh(I) kompleksleri (3a-5c) sentezlendi ve karakterizasyonları yapıldı. İyonik sıvılar 1 ve 2 yaklaşık %87, Metal-P-IL kompleksler ise 3a-3c % 85, 4a-4c % 90 ve 5b-5c % 89 verimle sentezlendi. Termal analiz sonuçları incelendiğinde 3a-4c komplekslerinin 138 ºC ile 194 ºC aralığında bozunmadan güvenli bir şekilde kullanılabileceği görüldü. 3a ve 3b Ru (II) komplekslerinin asetofenonun TH'daki katalitik aktivitesi incelendiğinde, reflaks sıcaklığında, 3a için 388 sa-1 ve 3b için 64 sa-1 TOF değeri elde edildi. Bu sonuçlar, Ru-benzen kompleksinin Ru-p-simen kompleksine göre daha iyi olduğunu göstermiştir. Ir (III) komplekslerinin TH sonuçları ise 3c için 45 dak. %98 dön. ve 131 sa-1 TOF değeri elde edilirken, 4c için 5 saatte %93 dön. ve 19 sa-1 TOF değeri elde edildi. Tüm komplekslerinin TH reaksiyonları incelendiğinde Ru-aren komplekslerinin daha iyi sonuçlar verdiği görülmüştür. 3a kompleksi için sübstitüe asetofenonun TH reaksiyonları incelendiğinde, 4-F asetofenon için 10 dak. %99 dönüşüm elde edilirken, 2-MeO asetofenon için 90 dak. %93 dönüşüm elde edildi. Geçiş metali içeren birçok kompleks, antimikrobiyal, antioksidan, antikanser gibi biyolojik aktivitelerdeki etkinliği nedeniyle ilgi çekmiştir. Birçok durumda metal kompleksi serbest liganddan daha iyi bir aktivite göstermiştir. % DPPH inhibisyon sonuçları incelendiğinde 4b nolu Ru (II) kompleksi 25 mg L-1' de % 24.19 radikal süpürme aktivite gösterirken, 200 mg L-1'de % 72.27 radikal süpürme aktivitesi göstermiştir. Ayrıca, 4b nolu test bileşiği diğer test bileşiklerine göre tüm konsantrasyonlarda en yüksek aktiviteyi göstermiştir. Test bileşiklerinin tümü kayda değer şelatlama aktivitesi göstermemiştir. Test bileşiklerinin tümü çalışmada kullanılan beş bakteri (E. coli (ATCC 10536), P. aeruginosa (ATCC 9027),S.aureus (ATCC 6538), E. hirea (ATCC 10541), B. cereus) üzerine değişen düzeylerde antibakteriyel etki göstermiştir. Sentezlenen imidazol içeren türevler (1-4c) içerisinde en yüksek antibakteriyel aktiviteyi Ir (III) geçiş metali içeren 4c bileşiği gösterirken (13 mm), vinil grubu içeren iyonik sıvı (1) hiç bir antibakteriyel aktivite göstermemiştir. The first study on an ionic liquid (IL) was carried out in 1914 by Paul Walden, who observed certain physical properties of ethylammonium nitrate ([EtNH3][NO3]; mp 13–14 °C). The discovery of a new class of materials did not receive much attention at the time, but today this work is generally accepted as the starting point for the field of ionic liquids. Ionic liquids are widely used as catalysts or reaction media in organic synthesis due to their environmentally friendly chemical and physical properties and especially their structural adjustability. In the present study, two ionic liquids 3-(3-chloro-2-hydroxypropyl)-1-vinyl-1H-imidazole-3-ium chloride (1) and 3-(3-chloro-2-hydroxypropyl)-1-butyl-1H-imidazole-3-ium chloride (2) was synthesized according to the literature. Phosphinite ligands 3, 4, and 5 were synthesized by reacting the imidazole derivative ionic liquids with PPh2Cl or PCy2Cl at -78 °C using the Schlenk-line technique. Since the ligands are unstable, they could not be characterized. Nevertheless, Ru (II), Ir (III) and Rh(I) complexes (3a-5c) of the phosphinite ligands were synthesized and characterized. Ionic liquids 1 and 2 were synthesized in approximately 87 % yield, while Metal-P-IL complexes were synthesized in 85% yields for 3a-3c, 90% for 4a-4c, and 89% for 5b-5c. When the thermal analysis results were considered, it was observed that the 3a-4c complexes could be safely used without decomposition between 138 ºC and 194 ºC. When the catalytic activity of Ru (II) complexes 3a and 3b was investigated in TH of acetophenone, TOF value of 388 h-1 and 64 h-1 were obtained for 3a and 3b, respectively, at reflux temperature, indicating that Ru-benzene complex was more efficient than Ru-p-cymene complex. When the TH results of Ir (III) complexes were examined, 98% conversion was obtained for 3c in 45 min, while 93% conversion was obtained for 4c in 5 h. When the TH reactions of all complexes were considered, it was observed that Ru-arene complexes gave better results. When the TH reactions of substituted acetophenone for the 3a complex were investigated, it was seen that 99% conversion was obtained for 4-F acetophenone in 10 min, while 93% conversion was obtained for 2-MeO acetophenone in 90 min. Many complexes containing transition metals have attracted attention due to their effectiveness in biological activities such as antimicrobial, antioxidant, and anticancer. In many cases the metal complex showed better activity than the free ligand. When the % DPPH inhibition results were taken into account, it was observed that Ru (II) complex 4b showed 24.19% radical scavenging activity at 25 mg L-1, while it showed 72.27% radical scavenging activity at 200 mg L-1. Test compound 4b showed the highest activity at all concentrations compared to other test compounds. All test compounds showed no significant chelating activity. All of the test compounds showed varying levels of antibacterial activity on the five bacteria used in the study (E. coli (ATCC 10536), P. aeruginosa (ATCC 9027), S. aureus (ATCC 6538), E. hirea (ATCC 10541), B. cereus). Among the synthesized imidazole containing derivatives (1-4c), compound 4c containing Ir (III) transition metal exhibited the highest antibacterial activity (13 mm), while ionic liquid including vinyl group (1) showed no antibacterial activity. Dicle Üniversitesi Bilimsel Araştırma Projeleri Koordinatörlüğü (DÜBAP) tarafından FEN20.001 no‘lu proje kapsamında ve TÜBİTAK 2211 Yurt içi Lisansüstü Burs Programı ile desteklenmiştir.

The interaction of [Ru(η6-arene)(μ-Cl)Cl]2 and Ir(η5-C5Me5)(μ-Cl)Cl]2 with a new Ionic Liquid-based phosphinite ligand, [(Ph2PO)-C6H9N2Ph]Cl, (2) gave [Ru((Ph2PO)-C6H9N2Ph)(η6-p-cymene)Cl2]Cl (3), [Ru((Ph2PO)-C6H9N2Ph)(benzene)Cl2]Cl (4) and [Ir((Ph2PO)-C6H9N2Ph)(C5Me5)Cl2]Cl (5), complexes. All the compounds were characterized by a combination of multinuclear NMR and IR spectroscopy as well as elemental analysis. Furthermore, the Ru(II) and Ir(III) catalysts were applied to asymmetric transfer hydrogenation of acetophenone derivatives using 2-propanol as a hydrogen source. The results showed that the corresponding alcohols could be obtained with good activity (up to 55% ee and 99% conversion) under mild conditions. Notably, [Ir((Ph2PO)-C6H9N2Ph)(C5Me5)Cl2]Cl (5) is more active than the other analogous complexes in the transfer hydrogenation (up to 81% ee).

We studied for the first time the potential of novel and simple Ir/thioether-NHC complexes in the asymmetric hydrogenation of unfunctionalized olefins and cyclic β-enamides. For comparison, we prep...

The present report describes the results of a combined experimental and computational study on the mechanism of aryl phosphinite cyclonickelation. The reaction of ArOP(i-Pr)2 with [(i-PrCN)NiBr2]n proceeds more readily in acetonitrile relative to toluene; this is because the greater nucleophilicity of acetonitrile toward Ni stabilizes a more reactive acetonitrile adduct bearing one phosphinite ligand (as opposed to two). A sufficiently strong external base such as Et3N serves to quench the HBr generated at the nickelation step, thus allowing isolation of the cyclonickelated species. However, nickelation tests conducted in the absence of external base revealed that D/H scrambling occurs at the ortho positions of C6D5OP(i-Pr)2, implying that the cyclonickelation proceeds independently of the base. Thus, the main role of the external base is to prevent protonation of the Ni–aryl moiety formed via C–H nickelation. Tests have also shown that nickelation rates are affected by the quantity of the base used: the ...

In order to explore the boron mediated C-S bond activation of the thiolate ligand in transition metal thiolate complexes, several bis(phosphinite) (POCOP) pincer ligated palladium complexes bearing a benzylthiolate or mercapto auxiliary ligand, [2,6-(R2PO)2C6H3]PdY (Y = SCH2Ph, R = tBu, 1a, iPr, 1b; Y = SH, R = tBu, 2a, iPr, 2b), were synthesized and fully characterized by multinuclear NMR, FTIR, X-ray crystallography and elemental analysis. The reactions of complexes 1a-b or 2a-b with BH3·THF at room temperature produced exclusively the corresponding tetrahydroborate complexes, [2,6-(R2PO)2C6H3]Pd(η1-HBH3) (R = tBu, 3a; iPr, 3b), through Pd-S bond cleavage. Complexes 3a and 3b are air/moisture sensitive and thermally unstable. X-ray crystallography and FTIR spectra supported a η1-HBH3 monodentate coordination mode for the BH4 ligand in complexes 3a and 3b. The boron mediated C-S bond cleavage was not observed in the reactions of complexes 1a and 1b with BH3·THF perhaps due to the relatively weak Pd-S bond.

Two Ru(II) complexes were synthesized by reaction of phosphinite-functionalized imidazolium salts [(Ph2PO)C7H11N2Cl]Cl (1) and [(Cy2PO)C7H11N2Cl]Cl (2) with 1/2 equivalent of [Ru(η6-p-cymene)(µ-Cl)Cl]2 in anhydrous CH2Cl2 and under argon atmosphere. The complexes were then isolated as analytically pure substances and characterized using multinuclear NMR and infrared spectroscopies and elemental analysis. The Ru(II) compounds were used to study their biological assay. For this purpose, radical scavenging, reducing power, antibacterial activity, DNA binding, and DNA cleavage activity were fully studied. The maximum 1,1-diphenyl-2-picrylhydrazyl radicals (DPPH) scavenging (78.9%) and reducing power were obtained from compound 4 at the concentration of 200 µg/ml. The compounds were also tested against three Gram-positive and three Gram-negative bacteria, and they were found to be more effective against Gram-positive bacteria. In addition, both compounds showed excellent DNA binding and DNA cleavage activity.

Organometallic chemists usually like to use the word robust to describe pincer ligand frameworks in metal pincer complexes. Although most transition metal pincer complexes are thermally stable, the pincer backbone frameworks can still decompose under certain circumstances. In order to explore the stability of the bis(phosphinite) (POCOP) pincer backbone in transition metal pincer complexes, group 10 metal POCOP pincer complexes were exposed to different nucleophilic and electrophilic conditions, respectively. It was found that the POCOP pincer backbone is stable under intermolecular nucleophilic conditions but cannot survive intramolecular nucleophilic attack; the POCOP pincer backbone is also stable under weak electrophilic conditions but the backbone can be completely destroyed by strong Lewis acids such as AlCl3. Possible decomposition/reconstruction pathways of the POCOP pincer ligand framework were proposed.

Nickel(II) chloride and thiolate complexes with iPrPE1CE2PiPr (E = O, S) pincer ligands were investigated as electrocatalysts for the hydrogen evolution reaction in CH3CN in the presence of acetic acid and trifluoroacetic acid. The bis(thiophosphinite) (S,S) chloride complex reduced protons at the lowest overpotential in comparison with the bis(phosphinite) (O,O) and mixed phosphinite–thiophosphinite (O,S) complexes. A combination of electrochemical, NMR and UV-vis spectroscopic and mass spectrometric experiments provides mechanistic insights into the catalytic cycle for proton reduction to dihydrogen.

The chromophore class of 1,3,8,10‐tetrasubstituted peropyrenes was effectively synthesized from peropyrenequinone via a Zn‐mediated reductive aromatization approach. In one step, a symmetric functionalization of the peropyrene backbone introducing silylethers (2,3), pivaloyl (4), triflyl (5) and also phosphinite (6) groups was established. Furthermore, the potential of using 4 and 5 in transition metal catalysed cross couplings was explored leading to 1,3,8,10‐tetraaryl (8‐11) and tetraalkynyl (7) peropyrenes. The influence of various substituents on the optoelectronic properties of these π‐system extended peropyrenes was investigated in solid state by means of X‐ray crystallography, in solution by means of UV‐Vis and fluorescence spectroscopy and by their redox properties studied via cyclic voltammetry. By comparison with DFT and TD‐DFT calculations, it could be elucidated that introduction of a broad variety of substituents in such versatile one or two step procedures leads to peropyrenes with easily tunable HOMO and LUMO energies ranging in a gap window of 0.8 eV. The frontier molecular orbital energies identify the target molecules as promising candidates for hole transporting semiconductors., 1,3,8,10‐Tetrasubstituted peropyrenes were synthesized via a reductive aromatization and functionalization strategy. Finetuning of their optoelectronic properties was monitored by UV‐Vis, PL, XRD, CV, and DFT methods.

BOM-tert-butylmethylphosphinite borane is an efficient electrophilic P-stereogenic transfer reagent for the synthesis of bulky tertiary phosphines. The novel methodology relies on a one-pot deprotection/substitution process. The substitution of the trivalent phosphinite takes place with high stereospecificity and provides the products with inversion of configuration at the phosphorus atom. The potential of the methodology is demonstrated with the synthesis of a wide scope of tertiary phoshines in excellent enantiomeric excess. Finally the methodology was applied to the synthesis of bulky P-stereogenic BisP* ligand analog.

Cette thèse présente différents aspects de la cyclonickellation des phosphinites de type Aryl-OP(i-Pr)2, leur potentiel dans la fonctionnalisation et leur utilité pour former des nouveaux types de complexes de types pincer de nickel. Le Chapitre 1 constitue une introduction générale sur l’importance de la liaison carbone-nickel en chimie organométallique. Diverses stratégies de formation des liens C-Ni dans des composés classiques (monodentés), des composés de types pincer (tridentés) et des composé cyclonickellés (bidentés et tridentés) y sont présentées, incluant des réactions impliquant des précurseurs de Ni0, de NiII ou de NiIV. Ce chapitre présente également la réactivité de ces composés comportant des liens C-Ni, et met l’emphase sur la réactivité des liaisons carbone-nickel, en particulier dans les processus catalytiques destinés à la fonctionnalisation des liens C-H, en utilisant des groupes directeurs. Les phosphinites sont ensuite présentées comme des groupes directeurs intéressants en catalyse, bien qu’elles aient surtout été utilisé avec d’autres métaux que le nickel. La dernière partie de ce chapitre pose les questions qui tenterons de trouver réponse dans les travaux présentés aux chapitres suivants. Les Chapitres 2 et 4, basés sur des articles publiés, présentent l’isolation et la caractérisation de composés dimériques de type [{κP,κC-(i-Pr)2POAr}Ni(μ-Br)]2 issus de l’ortho-nickellation des phosphinites dérivées des phénols et des naphtols substitués, ainsi que de certains de leurs adduits monomériques d’acétonitrile ou du ligand lui-même. Ces discussions cherchent à répondre à la question de régiosélectivité de la cyclonickellation : on y démontre que cette réaction est gouvernée par les facteurs stériques, menant à la métallation préférablement (pour les substituants fluor) ou exclusivement (pour les substituants plus volumineux) aux carbones les moins encombrés, lorsque deux positions ortho sont disponibles, et que la réaction mène toujours à la formation de nickellacycles à 5 chainons. Ainsi, les phénols C3-substitués subissent la métallation au carbone C6, alors que les 1- et 2-naphtols subissent la nickellation aux positions C2 et C3, respectivement. Ces deux chapitres démontrent que la métallation peut avoir lieu sur des carbones qui possèdent déjà un voisin encombrant (F, OMe, benzo), menant à des structures relativement distordues, mais que la nickellation n’est pas produite dans les conditions standard au voisinage des substituants Me et Cl qui sont plus volumineux, ni au carbone C8 du 1-naphtol qui mènerait à un nickellacycle à 6 chainons. L’étude structurale permet de rationaliser les régiosélectivités observées, et les études par diverses méthodes RMN complètent la caractérisation de ces nouveaux composés. Le Chapitre 2 démontre que lorsque les sites potentiels de nickellation sont bloqués par des substituants ortho Me ou Ph, la réaction ne prend pas place sur ces substituants en raison de la formation de nickellacycles à 6 ou 7 chainons respectivement. Ceci met en lumière également l’impossibilité d’isoler les composés nickellés aux carbones sp³ des substituants ortho, et le Chapitre 4 démontre par des expériences d’échange H/D que la nickellation à ces positions n’est pas seulement thermodynamiquement défavorisée, mais qu’elle est aussi cinétiquement inexistante. Ce chapitre dévoile également les réactions qui sont observables à 80 °C sont radicalement accélérées à haute température (120 ou 160 °C), et que les produits de nickellation y sont thermodynamiquement stables. Le Chapitre 4 présente également une réaction de fonctionnalisation in situ des liens carbone-nickel de la phosphinite cyclonickellée dérivée du 1-naphthol. Dans cette réaction, qui se produit à haute température en absence de base, la bromophosphine Br-P(i-Pr)2 se génère in situ et permet l’insertion formelle d’un phosphènium [(i-Pr)2P]+ dans le lien carbone-nickel, menant à un complexe phosphine-phosphinite de type {κP,κP’-1-(i-Pr)2PO-2-naphtyl-P(i-Pr)2}NiBr2. Lorsque la position C2 du 1-naphtol est bloquée par un substituant Et, un genre similaire de fonctionnalisation à la position C8 est observé, menant à l’obtention de 8-(i-Pr)2P(O)-2-Et-1-naphtol, ainsi qu’à des sous-produits qui ont été identifiés et caractérisés. Cette réaction démontre l’accessibilité cinétique de la position C8 à haute température, mais démontre également l’instabilité du nickellaycle généré. Les conditions réactionnelles pour l’obtention des phosphinites nickellées dévoilées au Chapitre 2 (utilisant l’acétonitrile comme solvant) ont démontré une efficacité supérieure que celle présentée précédemment (dans le toluène). Ainsi, le Chapitre 3, également basé sur un article publié, cherche à décrire les aspects mécanistiques de cette cyclométallation et démontre que les espèces initialement présentes dans l’acétonitrile sont des adduits mono-phosphinites du nickel au contraire des espèces présentes dans le toluène. Cette étude démontre qu’une base externe est nécessaire pour conduire à l’isolation des composés nickellés, mais qu’elle n’est pas impliquée dans le mécanisme de métallation car la formation des liens C-Ni se produit réversiblement en absence de base. Des suivis cinétiques indiquent que la réaction est de premier ordre et qu’un excès de base ralentit la réaction en formant des espèces non réactives, et que les bases idéales sont fortes et peu coordonnantes. Une étude mécanistique expérimentale révèle que l’étape de nickellation est de nature électrophile (pente de Hammett ρ ≈ –4) et associative (ΔH⧧ = 18(1) kcal·mol–1 and ΔS⧧ = −27(4) cal·mol–1·K–1) et que le transfert de proton est l’étape limitante (kH/kD ≈ 11). Ces résultats sont appuyés par une étude computationnelle par DFT qui démontre que la dissociation d’un ligand Br- mène à une paire d’ions comme intermédiaire, depuis lequel la déprotonation est réalisée par l’anion Br- dans un mécanisme de type CMD. Les résultats de ces calculs théoriques permettent également d’appuyer la thèse d’un état fondamental triplet pour les espèces présentes avant la nickellation dans l’acétonitrile. Les études sur la régiosélectivité ont mené à un résultat surprenant : à la place de subir la nickellation C-H, la phosphinite dérivée du 2-vinylphénol subit une attaque nucléophile sur le groupe vinyle afin de donner un composé tridenté portant un lien Csp³-Ni. Le Chapitre 5 présente ainsi une nouvelle stratégie de préparation des composés pincers par des réactions de type Umpolung. Le ligand 2-vinylphényl-OP(i-Pr)2 réagit avec des amines et des phosphines portant au moins un proton, pour donner des complexes pinceurs de type 6,4-POCY-NiBr (Y = P, N). Ce chapitre dévoile l’étendue des composés qui peuvent être produits par cette méthode, et offre une caractérisation de ces composés par RMN, diffraction des rayons X et par électrochimie, afin de comparer leurs caractéristiques avec les autres pincers décrits dans la littérature. Enfin, alors que le Chapitre 6 présente quelques résultats additionnels reliés aux divers axes de recherche de cette thèse, le Chapitre 7 rappelle les grandes lignes des découvertes présentées aux Chapitres 2-5. Ce chapitre de conclusion générale présente également des perspectives basées sur les résultats de la thèse, et sur les quelques résultats préliminaires. Au menu : une discussion sur la relation entre régiosélectivité et la stabilité, des nouvelles stratégies de nickellation à étudier (à partir de liens carbone-halogène), la fonctionnalisation des liens C-Ni par des composés isolobaux aux phosphèniums et des stratégies pour la fonctionnalisation des oléfines dans les composés de type alcool., This thesis presents various aspects of the cyclonickelation of phosphinites Aryl-OP(i-Pr)2, as well as their potential in functionalization processes and applications in the preparation of new types of pincer-Ni complexes. Chapter 1 consists of a general introduction on the importance of the carbon-nickel bond in organometallic chemistry. Various strategies leading to C-Ni bonds in classical (monodentate) compounds, pincer complexes (tridentate), and cyclonickelated species (bi- and tridentate) are disclosed, including reactions implicating Ni0, de NiII ou de NiIV precursors. This chapter also presents the reactivity of species featuring C-Ni bonds C-Ni and underlines the reactivity of C-Ni bonds, especially in catalytic processes targeting C-H bonds functionalization, through the use of directing groups. Next, phosphinites are displayed as interesting directing groups in catalysis even though they have been used mostly with metals other than nickel. The last part of this chapter outlines the questions that are meant to be addressed in the next chapters. Chapters 2 and 4, based on published articles, display the isolation and characterization of dimeric complexes of the type [{κP,κC-(i-Pr)2POAr}Ni(μ-Br)]2 arising from the ortho-nickelation of phosphinites derived from substituted phenols and naphthols, as well as some of their acetonitrile or phosphinite adducts. These studies are meant to address the question of regioselectivity in the cyclonickelation. The results obtained prove that when two ortho sites are available for reactivity, the nickelation is governed by steric factors and leads to metalation preferably (in case of F substituents) or exclusively (in case of larger substituents) at the least hidered C-H bond; moreover, the nickelation always leads to 5-membered nickelacycles. Thus, C3-substituted phenols undergo nickelation at the C6 position, while 1- and 2-naphthols undergo nickelation at C2 and C3 positions, respectively. Together, Chapters 2 and 4 show that metalation can take place at the carbon next to a F-, MeO- or benzo substituent, but such nickelation at the hindered sites leads to distorted structures in the products. One the other hand, nickelation never occurs at carbons neighbouring the larger Me- or Cl- substituents, nor at the C8 position of 1-naphthol which would lead to a 6-membered nickelacycle. The structural study allows us to rationalize the observed regioselectivities, and NMR studies complete the characterization of these new compounds. Chapter 2 also reveals that when the ortho sites are blocked by Me or Ph functional groups, no nickelation takes places on these substituents due to the unfavored generation of 6- or 7-membered metallacycles, respectively. This finding also rationalizes why it has not been possible to isolate complexes arising from the nickelation at sp³ carbons of ortho substituents. This point is confirmed in the studies described in Chapter 4, which shows how H/D exchange experiments helped us prove that reactivity at these aliphatic C-H sites is disfavored not only thermodynamically, but also kinetically. This chapter also reveals that reactions observed at 80 °C can be accelerated dramatically at higher temperatures (120 or 160 °C), and that nickelated products are stable in these conditions. Chapter 4 also presents some examples of in situ functionalization of the C-Ni bonds in cyclonickelated 1-naphthyl phosphinites. Conducting these reactions in the absence of base at high temperatures allowed the in situ generation of bromoposphine, Br-P(i-Pr)2, that promotes the formal insertion of a phosphenium fragment [(i-Pr)2P]+ into the C-Ni bond, thus leading to a phosphine-phosphinite complex of Ni, of the following formula: {κP,κP’-1-(i-Pr)2PO-2-naphtyl-P(i-Pr)2}NiBr2. When the C2 position in the naphthyl phosphinite is blocked by an Et substituent, a similar functionalization occurs at the C8 position leading to 8-(i-Pr)2P(O)-2-Et-1-naphtol, along with by-products which have been identified and characterized. These findings demonstrated the kinetic accessibility of the C8 position at high temperatures, while proving the instability of the generated nickelacycle. The reaction conditions used for the syntheses of cyclonickelated phosphinites displayed in Chapter 2 (using acetonitrile as the solvent) have been proven more efficient than that previously reported (in toluene). Thus, Chapter 3, also based on a published article, describes the mechanistic aspects of the new procedure and reveals that acetonitrile generates more reactive species at the pre-nickelation stage, namely mono-phosphinite nickel adducts, as opposed to the bis-phosphinite nickel complexes observed in toluene. This study demonstrates that an external base is required for isolating the nickelated complexes, but that this base is not implicated in the metalation process, since the formation of the C-Ni bond occurs reversibly in the absence of base. Kinetic monitoring reveals that the reaction is 1st order and that an excess of base in fact slows down the rate by generating non-reactive species. Ideal bases for the nickelation are thus strong bases but weakly coordinating nucleophiles. An experiment-based mechanistic investigation shows that the nickelation is of electrophilic (Hammett slope ρ ≈ –4) and associative (ΔH⧧ = 18(1) kcal·mol–1 and ΔS⧧ = −27(4) cal·mol–1·K–1) nature, and that the proton transfer is rate limiting (kH/kD ≈ 11). These results are supported by a DFT-based computational study that points towards an ion pair formation that allows the dissociated Br- anion to capture the proton, in a CMD mechanism. The theoretical calculation also supported a triplet ground state in acetonitrile for the species present in the pre-nickelation mixture in acetonitrile. Regioselectivity studies of a phosphinite bearing an ortho-vinyl substituent led to a surprising finding: instead of undergoing C-H nickelation, the phosphinite derived from 2-vinylphenol is attacked by nucleophiles on the vinyl moiety and give a Ni complex featuring a tridentate pincer-type ligand with a central Csp³-Ni bond. Chapter 5 thus discloses a new Umpolung-based strategy leading to new pincer complexes. Reaction of the ligand 2-vinylphenyl-OP(i-Pr)2 with primary or secondary amines and phosphines produces novel pincer-Ni complexes of the type 6,4-POCsp3Y-NiBr (Y = P, N). This chapter discloses the variety of new complexes that can be prepared by this new synthetic strategy. The characterisation of the new complexes by NMR, XRD and electrochemical analysis allowed us to compare their structural and redox properties to pincer-Ni complexes reported in the literature. While Chapter 6 discloses additional results related to various research axes of this thesis, Chapter 7 recalls the main findings revealed in Chapters 2-5. This conclusion also discloses research perspectives based on the results presented in this thesis, as well as phosphinite-related preliminary results gathered during my Ph. D. studies. The main proposed ideas touch on the following aspects: (a) the relationship between regioselectivity and stability towards functionalization; (b) new nickelation strategies based on the metalation of carbon-halogen bonds; (c) C-Ni functionalization by isolobal compounds to phosphenium ions; and (d) strategies towards the functionalization of alcohols bearing alkene moieties.

New and readily available chiral SPIROL-based diphosphinite ligands (SPIRAPO) have been prepared and employed for iridium-catalyzed asymmetric hydrogenations of quinolines, quinoxalines and 2H-1,4-bezoxazin-2-ones. While the structurally similar (R,R,R)-SPIRAPO and (R)-SPINOL-based phosphinites were not the best ligands for these transformations, the (S,R,R)-diastereomer of SPIRAPO was found to be highly effective ligand for the reduction of 20 different heterocyclic systems with loadings as low as S/C = 10 000. This dearomatizative hydrogenation provided direct access to optically active tetrahydroquinolines in high enantioselectivities (up to 94% ee) and excellent yields (up to 99%), and was used to generate 1.75 g of natural alkaloid (−)-(R)-angustureine. This protocol was subsequently extended to achieve asymmetric hydrogenation of quinoxalines and 2H-1,4-benzoxazin-2-ones in good to excellent enantioselectivities.

International audience; We have recently patented an unprecedented stereospecific N→O phosphinyl migration process which transforms P-chirogenic aminophosphines into phosphinites. A fine design of aminophosphine phosphinite ligands (AMPP*) derived from ephedrine and bearing a P-chirogenic center either at the aminophosphine or phosphinite moiety, was performed. The synthesis of AMPP* ligands with P-chirogenic aminophosphine moiety was based on the well-established stereospecific reaction of oxazaphospholidine-borane with organolithium reagents, followed by trapping with a chlorophosphine and borane decomplexation. Concurrently, the preparation of AMPP* ligands with P-chirogenic phosphinite moiety were performed by N→O phosphinyl migration of aminophosphines borane by heating at 50 °C with DABCO, and then reaction with chlorophosphines. AMPP* ligands were studied in palladium-catalyzed asymmetric allylic alkylations, leading to enantioselectivities from 91% (R) to 95% e.e. (S). X-ray crystallographic data for relevant Pd-AMPP* complexes and computer modeling explained the origin of the enantioselectivities based on MO interactions of most stable conformers with nucleophiles.

New chiral C2-symmetric bis(phosphinite) ligands containing imine group were synthesized from 1-({[(1R,2R)-2-{[(2-hydroxynaphthalen-1-yl)methylidene] amino}cyclohexyl]- imino}methyl)- naphthalen-2-ol and two equivalents of Ph2PCl, (i-Pr)2PCl or (Cy)2PCl, in high yields. Binuclear C2-symmetric half sandwich η6-p-cymene-Ru(II) complexes of the chiral phosphinite ligands were synthesized by treating of [Ru(η6-p-cymene)(μ-Cl)Cl]2 with the phosphinites in 1:1 M ratio in CH2Cl2. Their catalytic activities in asymmetric transfer hydrogenation (ATH) were investigated for the reaction of acetophenone derivatives with isopropyl alcohol. The corresponding optically active secondary alcohols were obtained in excellent levels of conversion (96–99%) and moderate enantioselectivity (up to 60% ee). Among three complexes investigated, complex 4 was the most efficient one.

Lung cancer is one of the major causes of cancer-related deaths in the world. Non-small-cell lung cancer (NSCLC) is the most common type of lung cancer, and small-cell lung cancer (SCLC) is the most aggressive subtype of lung cancer. Proper therapies for SCLC have not yet been developed. However, new molecules have been designed and big innovation in treating SCLC has been achieved. Platinum-based antitumor drugs like cisplatin and carboplatin have several disadvantages including side effects, cisplatin-resistant tumors and limited solubility in aqueous media. Thus, two novel chiral aminoalcohol-based bis(phosphinite) ligands containing (eta(6)-p-cymene)-Ru(II)-phosphinite and bis(phosphinite)-Pd(II) complexes were synthesized and evaluated for anticancer activity. In this study, the results showed that complex1has the strongest cytotoxic effects on SCLC and NSCLC cell lines. On the other hand, cisplatin, ruthenium and palladium complexes are capable to induce apoptosis. Especially, complexes1and2can induce apoptosis for both SCLC and NSCLC. When compared to the qRT-PCR and TUNEL results, we obtained a significant correlation between apoptotic index and p21, Bax gene expressions. This work revealed the potential of the synthesized complexes as anticancer agents with cytotoxic and pro-apoptotic activity as leading compounds for further anticancer researches. C1 [Tokgun, Onur; Karagur, Ege Riza; Akca, Hakan] Pamukkale Univ, Fac Med, Dept Med Genet, TR-20160 Denizli, Turkey. [Karakas, Duygu Elma] Siirt Univ, Sci & Technol Applicat & Res Ctr, TR-56100 Siirt, Turkey. [Tan, Semih] Pamukkale Univ, Fac Med, Dept Histol & Embryol, TR-20160 Denizli, Turkey. [Inal, Behcet] Siirt Univ, Agr Fac, Dept Agr Biotechnol, TR-56100 Siirt, Turkey. [Durap, Feyyaz; Baysal, Akin; Aydemir, Murat] Dicle Univ, Sci Fac, Dept Chem, TR-21280 Diyarbakir, Turkey.

This article belongs to the Special Issue Advances in Coordination Chemistry., A straightforward method for the preparation of trisphosphinite ligands in one step, using only commercially available reagents (1,1,1-tris(4-hydroxyphenyl)ethane and chlorophosphines) is described. We have made use of this approach to prepare a small family of four trisphosphinite ligands of formula [CH3C{(C6H4OR2)3], where R stands for Ph (1a), Xyl (1b, Xyl = 2,6-Me2-C6H3), iPr (1c), and Cy (1d). These polyfunctional phosphinites allowed us to investigate their coordination chemistry towards a range of late transition metal precursors. As such, we report here the isolation and full characterization of a number of Au(I), Ag(I), Cu(I), Ir(III), Rh(III) and Ru(II) homotrimetallic complexes, including the structural characterization by X-ray diffraction studies of six of these compounds. We have observed that the flexibility of these trisphosphinites enables a variety of conformations for the different trimetallic species., This research was funded by European Research Council (ERC Starting Grant, CoopCat, Project 756575), BBVA Foundation (Investigadores y Creadores Culturales 2016) and the Spanish Ministry of Science, Innovation and University (CTQ2017-92622-EXP).