Bulky Phosphine Ligands Research Articles

Aminative Suzuki-Miyaura coupling.

The Suzuki-Miyaura and Buchwald-Hartwig coupling reactions are widely used to form carbon-carbon (C-C) and carbon-nitrogen (C-N) bonds, respectively. We report the incorporation of a formal nitrene insertion process into the Suzuki-Miyaura reaction, altering the products from C-C-linked biaryls to C-N-C-linked diaryl amines and thereby joining the Suzuki-Miyaura and Buchwald-Hartwig coupling pathways to the same starting-material classes. A combination of a bulky ancillary phosphine ligand on palladium and a commercially available amination reagent enables efficient reactivity across aryl halides and pseudohalides, boronic acids and esters, and many functional groups and heterocycles. Mechanistic insights reveal flexibility on the order of bond-forming events, suggesting potential for expansion of the aminative cross-coupling concept to encompass diverse nucleophiles and electrophiles as well as four-component variants.

T-Shaped Palladium and Platinum {MNO}10 Nitrosyl Complexes.

The synthesis and characterization of a homologous series of T-shaped {MNO}10 nitrosyl complexes of the form [M(PR3)2(NO)]+ (M = Pd, Pt; R = tBu, Ad) are reported. These diamagnetic nitrosyls are obtained from monovalent or zerovalent precursors by treatment with NO and NO+, respectively, and are notable for distinctly bent M-NO angles of ∼123° in the solid state. Adoption of this coordination mode in solution is also supported by the analysis of isotopically enriched samples by 15N NMR spectroscopy. Effective oxidation states of M0/NO+ are calculated, and metal-nitrosyl bonding has been interrogated using DFT-based energy decomposition analysis techniques. While a linear nitrosyl coordination mode was found to be electronically preferred, the M-NO and P-M-P angles are inversely correlated to the extent that binding in this manner is prevented by steric repulsion between the bulky ancillary phosphine ligands.

Palladium catalyzed stereoselective intramolecular [3 + 2] cycloaddition reactions of (E) & (Z)-ene-vinylidenecyclopropanes.

A palladium-catalyzed ring-opening cyclization of (E) & (Z)-ene-vinylidenecyclopropanes has been developed via an intramolecular [3 + 2] cycloaddition process in the presence of a sterically bulky biaryl phosphine ligand, stereoselectively affording fused cis- & trans-bicyclo[4.3.0] skeletal products in good yields with a broad substrate scope and good functional tolerance. A plausible reaction mechanism was proposed on the basis of previous work and the DFT calculations.

Palladium-catalyzed selective C-C bond cleavage of keto-vinylidenecyclopropanes: construction of structurally rich dihydrofurans and tetrahydrofurans.

Palladium-catalyzed selective cleavage of the distal C-C bond and proximal C-C bond of keto-vinylidenecyclopropanes by altering the sterically bulky phosphine ligands has been realized. The proximal C-C bond cleavage can be achieved by using dtbpf as a phosphine ligand, affording bicyclic products containing dihydrofuran skeletons in good yields along with broad substrate scope. In proximal C-C bond cleavage reactions, the eight-membered cyclic palladium intermediate plays a key role in the reaction. The [3 + 2] cycloaddition of keto-vinylidenecyclopropanes through the distal C-C bond cleavage can be effectively accomplished with t BuXPhos as a phosphine ligand and ZnCl2 as an additive, delivering bicyclic products containing tetrahydrofuran skeletons in good yields. The further transformation of these bicyclic products has been demonstrated, and the reaction mechanisms of two different C-C bond cleavage reactions have been investigated by control experiments and DFT calculations.

Shape Selectivity in the Gold‐Catalyzed Hydration of Alkynes Using a Cavity‐Shaped Phosphine

AbstractA cavity‐shaped gold(I) complex derived from a bulky tri‐(ortho‐biaryl)‐phosphine ligand shows preferred selectivity towards terminal functionalities in the gold(I)‐catalysed hydration of alkynes under mild heating due to a well‐defined pocket as catalytic active site. The confinement‐induced size‐exclusion selectivity investigated for eight alkynes contrasts with other gold(I) complexes bearing bulky phosphine ligands that show reduced selectivity or even similar behaviour towards both internal and terminal alkynes. We also interrogate the potential of gold(III) derivatives for the same catalytic process.

Palladium-Catalyzed Arylation of Hydantoins with Aryl Chlorides Enabled by Ylide-Functionalized Phosphines (YPhos)

The hydantoin moiety is an important structural motif present in various pharmaceuticals. Palladium complexes bearing electron-rich, bulky ylide-functionalized phosphine (YPhos) ligands were found to catalyze the arylation of N-protected hydantoins with broadly available aryl chlorides. Selective monoarylations, sequential diarylations, and arylation-alkylation sequences have been achieved. In combination with stepwise deprotection strategies, this opens up an expedient access to a wide variety of hydantoins, including derivatives of the anticonvulsant drugs phenytoin and mephenytoin.

Hydroxyl-directed C–C bond activation of benzophenones for the O-acylation of phenols

We report that 2-hydroxyl benzophenones can be converted to phenyl salicylate esters by loss of an aryl group and O-acylation of the phenols. Iridium, cyclooctadiene, and bulky monodentate phosphine ligands catalyze the ketone C–C bond activation and fragmentation. We identified common side products in this process, which include C-acylation of the phenol reactant or trapping on cyclooctadiene. Several of the processes reported here appear to be under equilibrium control. Overall, our report provides insight into the activation and functionalization of unstrained C–C bonds with group 9 catalysts.

Sterically Hindered 2‐(2’‐Hydroxyphenyl)benzoxazole (HBO) Emitters: Synthesis, Spectroscopic Studies, and Theoretical Calculations

AbstractWe describe various synthetic pathways to introduce sterically hindered substituents (mesityl, 2,4,6‐triisopropylphenyl, anthracene) to the proton donor side of excited‐state intramolecular proton transfer (ESIPT)‐capable 2‐(2’‐hydroxyphenyl) benzoxazole (HBO) fluorophores. Two original synthetic approaches were investigated in order to synthesize seven HBO derivatives. Optimization studies concluded that electron rich and bulky phosphine ligands are required to ensure completion of the Suzuki‐Miyaura cross‐coupling reaction involving a bulky aromatic boronic acid. The photophysical properties of all dyes revealed a strong influence of the nature of the solvent on the optical properties, as protic solvents tend to stabilize enol tautomers and induce dual emission. Our studies confirmed that, unlike the majority of organic dyes, ESIPT fluorophores do not undergo π‐stacking in the solid‐state. The nature of the excited‐states was explored by ab initio calculations.

Dicoordinate Au(I)-Ethylene Complexes as Hydroamination Catalysts.

A series of gold(I)–ethylene π-complexes containing a family of bulky phosphine ligands has been prepared. The use of these sterically congested ligands is crucial to stabilize the gold(I)–ethylene bond and prevent decomposition, boosting up their catalytic performance in the highly underexplored hydroamination of ethylene. The precatalysts bearing the most sterically demanding phosphines showed the best results reaching full conversion to the hydroaminated products under notably mild conditions (1 bar of ethylene pressure at 60 °C). Kinetic analysis together with density functional theory calculations revealed that the assistance of a second molecule of the nucleophile as a proton shuttle is preferred even when using an extremely congested cavity-shaped Au(I) complex. In addition, we have measured a strong primary kinetic isotopic effect that is consistent with the involvement of X–H bond-breaking events in the protodeauration turnover-limiting step.

Palladium-catalyzed cyclobutenation of aryl chlorides with norbornenes

A palladium-catalyzed cyclobutenation of readily available aryl chlorides and norbornene derivatives is reported here. Under the optimum reaction conditions, various valuable benzocyclobutene derivatives were prepared efficiently via Heck-Catellani reaction. The key is the employment of bulky t-Bu3PHBF4 phosphine ligand which promoted C–C reductive elimination from the palladacycle.

Rhodium‐Catalyzed meta‐Selective C−H Carboxylation Reaction of 1,1‐Diarylethylenes via Hydrorhodation‐Rhodium Migration

AbstractA meta‐selective C−H carboxylation reaction of 1,1‐diarylethylene derivatives with CO2 by using a rhodium catalyst with NaOiPr as a stoichiometric reductant has been achieved. Together with hydrogenation of the ethylene moiety, a carboxyl group was introduced to the meta‐position of the aryl ring with high selectivity over the ortho‐positions. Experimental and computational mechanistic studies indicate that this carboxylation reaction proceeds via hydrorhodation on the ethylene moiety, followed by 1,4‐rhodium migration and successive 1,2‐rhodium migration on the aryl ring. The use of a bulky phosphine ligand seems to be the key to this unusual aryl‐to‐aryl 1,2‐rhodium shift.

Rhodium-Catalyzed meta-Selective C-H Carboxylation Reaction of 1,1-Diarylethylenes via Hydrorhodation-Rhodium Migration.

A meta-selective C-H carboxylation reaction of 1,1-diarylethylene derivatives with CO2 by using a rhodium catalyst with NaOi Pr as a stoichiometric reductant has been achieved. Together with hydrogenation of the ethylene moiety, a carboxyl group was introduced to the meta-position of the aryl ring with high selectivity over the ortho-positions. Experimental and computational mechanistic studies indicate that this carboxylation reaction proceeds via hydrorhodation on the ethylene moiety, followed by 1,4-rhodium migration and successive 1,2-rhodium migration on the aryl ring. The use of a bulky phosphine ligand seems to be the key to this unusual aryl-to-aryl 1,2-rhodium shift.

Suzuki-Miyaura cross-coupling of 3,4-disubstituted 5-bromoisoxazoles: An efficient access to trisubstituted isoxazoles

The Suzuki-Miyaura cross-coupling of 3,4-disubstituted 5-bromoisoxazoles 1 at the C5 position has successfully proceeded in the presence of Pd2(dba)3 and P(t-Bu)3·HBF4 catalysts to give the corresponding trisubstituted isoxazoles 3 in good to high yields while suppressing the formation of ketone 4 as a byproduct. The use of bulky phosphine ligand P(t-Bu)3·HBF4 is essential for the current transformation, and the formation of ketone 4, which was a major product in the previous report, was able to be suppressed under the current conditions.

Cu23(PhSe)16(Ph3P)8(H)6]·BF4: Atomic-Level Insights into Cuboidal Polyhydrido Copper Nanoclusters and Their Quasi-simple Cubic Self-Assembly

Polyhydrido copper nanoclusters are an emerging class of nanomaterials. Unfortunately, insights into the structural evolution and structure–property relationship of such copper nanoclusters are scant, because of the difficulty of synthesizing and crystallizing nanoclusters with high nuclearity and new morphologies. Here, we report an anisotropic cuboidal polyhydrido copper nanocluster, [Cu23(PhSe)16(Ph3P)8(H)6]·BF4, with a distorted cuboctahedral Cu13 core stabilized by two square protecting motifs and six hydrides. The cuboidal nanoclusters self-assemble into a quasi-simple cubic packing pattern with perfect face-to-face contact of neighboring nanoclusters and interdigitation of intercluster surface ligands. Atomic-level observations reveal the crucial role that subtle synergies between nanocluster geometry and intercluster noncovalent interactions play in guiding nanocluster self-assembly. In addition, a comparison with previously reported analogous metal nanoclusters points to bulky monodentate phosphine ligands as a potent inducing agent for the formation of rectangular hexahedral nanoclusters. These findings have significant implications for the controllable synthesis of polyhedral nanomaterials and their superstructures.

Isolable dicarbon stabilized by a single phosphine ligand.

In contrast to naturally occurring F2, O2 and N2, diatomic C2 is an intriguing species that has only been observed indirectly in the gas phase, and because of its high reactivity has eluded isolation in the condensed phase. It has previously been stabilized in L→C2←L compounds but the bonding situation of the central C2 in this motif differs remarkably from that of free C2. Here we have prepared and structurally characterized diatomic C2 as a monoligated complex L→C2 using a bulky phosphine ligand bearing two imidazolidin-2-iminato groups (L is (NHCR=N)2(CH3)P, where NHCR is an N-heterocyclic carbene). The compound is stable in solution at ambient temperature and has also been isolated in the solid state. Reactivity studies, in combination with quantum chemical analysis, suggest that the two carbon atoms of the L→C2 complex both have carbene character. The complex underwent intermolecular C-H bond activation upon thermolysis and exhibited hydroalkoxylation-like reactivity with methanol.

Pd-Catalyzed (3 + 2) Heterocycloadditions between Alkylidenecyclopropanes and Carbonyls: Straightforward Assembly of Highly Substituted Tetrahydrofurans

A Pd catalyst made from a Pd(0) source and a bulky biaryl phosphine ligand promotes highly efficient intramolecular (3 + 2) heterocycloadditions between alkylidenecyclopropanes (ACPs) and carbonyls...

Recent advances in iridium(I) catalysis towards directed hydrogen isotope exchange.

The initial discovery and establishment of a family of novel iridium catalysts possessing N-heterocyclic carbene units alongside bulky phosphine ligands allowed selected substrates to be labelled using deuterium or tritium gas at desirably low catalyst loadings via an ortho-directed C-H insertion process. Such a method has broad applicability and offers distinct advantages within the pharmaceutical industry, directly facilitating the ability to carefully monitor a potential drug molecule's biological fate. Over the past decade since these initial protocols were divulged, many additional advances have been made in terms of catalyst design and substrate scope. This review describes the broadened array of new iridium catalysts and associated protocols for direct and selective C-H activation and hydrogen isotope insertion within a number of new chemical entities of direct relevance to the pharmaceutical industry.

Chemo- and Regioselective Synthesis of Acyl-Cyclohexenes by a Tandem Acceptorless Dehydrogenation-[1,5]-Hydride Shift Cascade

An atom-economical methodology to access substituted acyl-cyclohexenes from pentamethylacetophenone and 1,5-diols is described. This process is catalyzed by an iridium(I) catalyst in conjunction with a bulky electron rich phosphine ligand (CataCXium A) which favors acceptorless dehydrogenation over conjugate reduction to the corresponding cyclohexane. The reaction produces water and hydrogen gas as the sole byproducts and a wide range of functionalized acyl-cyclohexene products can be synthesized using this method in very high yields. A series of control experiments were carried out, which revealed that the process is initiated by acceptorless dehydrogenation of the diol followed by a redox-neutral cascade process, which is independent of the iridium catalyst. Deuterium labeling studies established that the key step of this cascade involves a novel base-mediated [1,5]-hydride shift. The cyclohexenyl ketone products could readily be cleaved under mildly acidic conditions to access a range of valuable substituted cyclohexene derivatives.

Mono- and dinuclear mimics of the [FeFe] hydrogenase enzyme featuring bis(monothiolato) and 1,3,5-triaza-7-phosphaadamantane ligands

Two new complexes [Fe2(µ-SC6H4CH3-p)2(CO)5(PTA)] 1 and [Fe(κ1-SC6H4CH3-p)2(CO)2(PTA)2] 2 with bis(monothiolato) ligands, resembling the active site of iron hydrogenases have been synthesized and analyzed for proton reduction activity using cyclic voltammetric techniques. The structure and geometry of the complexes have been studied by spectroscopic, crystallographic and computational analysis. The influence of bis(monothiolato) and bulky electron-donating phosphine ligands on electrocatalytic proton reduction process was examined. Both the complexes were found to be potent electrocatalysts with CECE or ECC(on S-atom)E (for 1) and CEEC(C) (for 2) mechanisms for hydrogen production.

Enantioselective hydrosilylation of unsaturated carbon-heteroatom bonds (C[double bond, length as m-dash]N, C[double bond, length as m-dash]O) catalyzed by [Ru-S] complexes: a theoretical study.

A detailed theoretical study on the mechanism of enanthioselective hydrosilylation of imines and ketones catalyzed by the ruthenium(ii) thiolate catalyst [Ru–S] ([L*-Ru(SDmp)]+[BAr4F]−) with a chiral monodentate phosphine ligand is carried out in this work. We elucidate all the pathways leading to the main products or by products mediated by the [Ru–S] complex in order to have deep understanding of the chemoselectivity and enantioselectivity. The DFT (Density Functional Theory) calculations show that the reaction mechanism including: (1) Si–H bond cleavage by the dual activity of Ru–S bond; (2) the generation of a sulfur-stabilized silane cation; (3) the electrophilic attack of silane cation to NC/OC; (4) hydrogen transfer from Ru to carbon cation. The hydrosilylation products are found to be the final products rather than the dehydrogenative ones, which is consistent with the experimental results. The dehydrogenative silylation reaction pathways which give N- or O-silylated enamine/enol ether are reversible according to our calculations. The computational results also show that the electrophilic attack of silicon to NC/OC is the rate-determining step and the ee value can be improved significantly with more bulky model phosphine ligand based on the same calculation methods.