Formation of exceptional monomeric YPhos-PdCl2 complexes with high activities in coupling reactions.

The use of well-defined palladium(ii) complexes as precatalysts for C-X cross-coupling reactions has improved the use of palladium catalysts in organic synthesis including large-scale processes. Whereas sophisticated Pd(ii) precursors have been developed in the past years to facilitate catalyst activation as well as the handling of systems with more advanced monophosphine ligands, we herein report that simple PdCl2 complexes function as efficient precatalysts for ylide-substituted phosphines (YPhos). These complexes are readily synthesized from PdCl2 sources and form unprecedented monomeric PdCl2 complexes without the need for any additional coligand. Instead, these structures are stabilized through a unique bonding motif, in which the YPhos ligands bind to the metal through the adjacent phosphine and ylidic carbon site. DFT calculations showed that these bonds are both dative interactions with the stronger interaction originating from the electron-rich phosphine donor. This bonding mode leads to a remarkable stability even towards air and moisture. Nonetheless, the complexes readily form monoligated LPd(0) complexes and thus the active palladium(0) species in coupling reactions. Accordingly, the YPhos-PdCl2 complexes serve as highly efficient precatalysts for a series of C-C and C-X coupling reactions. Despite their simplicity they can compete with the efficiency of more complex and less stable precatalysts.

A Mesoionic Carbene-Pyridine Bidentate Ligand That Improves Stability in Electrocatalytic CO2 Reduction by a Molecular Manganese Catalyst.

Tricarbonyl Group 7 complexes have a longstanding history as efficacious CO2 electroreduction catalysts. Typically, these complexes feature an auxiliary 2,2'-bipyridine ligand that assists in redox steps by delocalizing the electron density into the ligand orbitals. While this feature lends to an accessible redox potential for CO2 electroreduction, it also presents challenges for electrocatalysis with Mn because the electron density is removed from metal-ligand bonding orbitals. The results presented here thus introduce a mesoionic carbene (MIC) as a potent ligand platform to promote Mn-based electrocatalysis. The strong σ donation of the N,C-bidentate MIC is shown to help centralize the electron density on the Mn center while also maintaining relevant redox potentials for CO2 electroreduction. Mechanistic investigation supports catalytic turnover at two operative potentials separated by 400 mV. In the low operating potential regime at -1.54 V, Mn(0) species catalyze CO2 to CO and CO32-, which has a maximum rate of 7 ± 5 s-1 and is stable for up to 30.7 h. At higher operating potential at -1.94 V, "Mn(-1)" catalyzes CO2 to CO and H2O with faster turnovers of 200 ± 100 s-1, with the trade-off being less stability at 6.7 h. The relative stabilities of Mn complexes bearing MIC and 4,4'-di-tert-butyl-2,2'-bipyridine were compared by evaluation under the same electrolysis conditions and therefore elucidated that the MIC promotes longevity for CO evolution throughout a 5 h period.

From Stable PH-Ylides to α-Carbanionic Phosphines as Ligands for Zwitterionic Catalysts.

Although ylides are commonly used reagents in organic synthesis, the parent methylphosphine MePH2 only exists in its phosphine form in the condensed phase. Its ylide tautomer H3 P+ -CH2 - is considerably higher in energy. Here, we report on the formation of bis(sulfonyl)methyl-substituted phosphines of the type (RO2 S)2 C(H)-PR2, which form stable PH ylides under ambient conditions, amongst the first examples of an acyclic phosphine which only exists in its PH ylide form. Depending on the exact substitution pattern the phosphines form an equilibrium between the PH ylide and the phosphine form or exist as one of both extremes. These phosphines were found to be ideal starting systems for the facile formation of α-carbanionic phosphines. The carbanion-functionalization leads to a switch from electron-poor to highly electron-rich phosphines with strong donor abilities and high basicities. Thus, the phosphines readily react with different electrophiles exclusively at the phosphorus atom and not at the carbanionic center. Furthermore, the anionic nature of the phosphines allows the formation of zwitterionic complexes as demonstrated by the isolation of a gold(I) complex with a cationic metal center. The cationic gold center allows for catalytic activity in the hydroamination of alkyne without requiring a further activation step.

Tuning Ruthenium Carbene Complexes for Selective P-H Activation through Metal-Ligand Cooperation.

The use of iminophosphoryl-tethered ruthenium carbene complexes to activate secondary phosphine P-H bonds is reported. Complexes of type [(p-cymene)-RuC(SO2 Ph)(PPh2 NR)] (with R = SiMe3 or 4-C6 H4 -NO2 ) were found to exhibit different reactivities depending on the electronics of the applied phosphine and the substituent at the iminophosphoryl moiety. Hence, the electron-rich silyl-substituted complex undergoes cyclometallation or shift of the imine moiety after cooperative activation of the P-H bond across the M=C linkage, depending on the electronics of the applied phosphine. Deuteration experiments and computational studies proved that cyclometallation is initiated by the activation process at the M=C bond and triggered by the high electron density at the metal in the phosphido intermediates. Consistently, replacement of the trimethylsilyl (TMS) group by the electron-withdrawing 4-nitrophenyl substituent allowed the selective cooperative P-H activation to form stable activation products.

Au⋠⋠⋠H-C Hydrogen Bonds as Design Principle in Gold(I) Catalysis.

Secondary ligand-metal interactions are decisive in many catalytic transformations. While arene-gold interactions have repeatedly been reported as critical structural feature in many high-performance gold catalysts, we herein report that these interactions can also be replaced by Au⋅⋅⋅H-C hydrogen bonds without suffering any reduction in catalytic performance. Systematic experimental and computational studies on a series of ylide-substituted phosphines featuring either a PPh3 (Ph YPhos) or PCy3 (Cy YPhos) moiety showed that the arene-gold interaction in the aryl-substituted compounds is efficiently compensated by the formation of Au⋅⋅⋅H-C hydrogen bonds. The strongest interaction is found with the C-H moiety next to the onium center, which due to the polarization results in remarkably strong interactions with the shortest Au⋅⋅⋅H-C hydrogen bonds reported to date. Calorimetric studies on the formation of the gold complexes further confirmed that the Ph YPhos and Cy YPhos ligands form similarly stable complexes. Consequently, both ligands showed the same catalytic performance in the hydroamination, hydrophenoxylation and hydrocarboxylation of alkynes, thus demonstrating that Au⋅⋅⋅H-C hydrogen bonds are equally suited for the generation of highly effective gold catalysts than gold-arene interactions. The generality of this observation was confirmed by a comparative study between a biaryl phosphine ligand and its cyclohexyl-substituted derivative, which again showed identical catalytic performance. These observations clearly support Au⋅⋅⋅H-C hydrogen bonds as fundamental secondary interactions in gold catalysts, thus further increasing the number of design elements that can be used for future catalyst construction.

Towards the rational design of ylide-substituted phosphines for gold(i)-catalysis: from inactive to ppm-level catalysis.

The implementation of gold catalysis into large-scale processes suffers from the fact that most reactions still require high catalyst loadings to achieve efficient catalysis thus making upscaling impractical. Here, we report systematic studies on the impact of the substituent in the backbone of ylide-substituted phosphines (YPhos) on the catalytic activity in the hydroamination of alkynes, which allowed us to increase the catalyst performance by orders of magnitude. While electronic changes of the ligand properties by introduction of aryl groups with electron-withdrawing or electron-donating groups had surprisingly little impact on the activity of the gold complexes, the use of bulky aryl groups with ortho-substituents led to a remarkable boost in the catalyst activity. However, this catalyst improvement is not a result of an increased steric demand of the ligand towards the metal center, but due to steric protection of the reactive ylidic carbon centre in the ligand backbone. The gold complex of the thus designed mesityl-substituted YPhos ligand YMesPCy2, which is readily accessible in one step from a simple phosphonium salt, exhibited a high catalyst stability and allowed for turnover numbers up to 20 000 in the hydroamination of a series of different alkynes and amines. Furthermore, the catalyst was also active in more challenging reactions including enyne cyclisation and the formation of 1,2-dihydroquinolines.

Synthesis, Isolation and Crystal Structures of the Metalated Ylides [Cy3P-C-SO2Tol]M (M = Li, Na, K).

The preparation and isolation of the metalated ylides [Cy3PCSO2Tol]M ( Cy1-M) (with M = Li, Na, K) are reported. In contrast to its triphenylphosphonium analogue the synthesis of Cy1-M revealed to be less straight forward. Synthetic routes to the phosphonium salt precursor Cy1-H2 via different methods revealed to be unsuccessful or low-yielding. However, nucleophilic attack of the ylide Cy3P = CH2 at toluenesulfonyl fluoride under basic conditions proved to be a high-yielding method directly leading to the ylide Cy1-H. Metalation to the yldiides was finally achieved with strong bases such as nBuLi, NaNH2, or BnK. In the solid state, the lithium compound forms a tetrameric structure consisting of a (C-S-O-Li)4 macrocycle, which incorporates an additional molecule of lithium iodide. The potassium compound forms a C 4-symmetric structure with a (K4O4)2 octahedral prism as central structural motif. Upon deprotonation the P-C-S linkage undergoes a remarkable contraction typical for metalated ylides.

Efficient Pd-Catalyzed Direct Coupling of Aryl Chlorides with Alkyllithium Reagents.

Organolithium compounds are amongst the most important organometallic reagents and frequently used in difficult metallation reactions. However, their direct use in the formation of C-C bonds is less established. Although remarkable advances in the coupling of aryllithium compounds have been achieved, Csp2 -Csp3 coupling reactions are very limited. Herein, we report the first general protocol for the coupling or aryl chlorides with alkyllithium reagents. Palladium catalysts based on ylide-substituted phosphines (YPhos) were found to be excellently suited for this transformation giving high selectivities at room temperature with a variety of aryl chlorides without the need for an additional transmetallation reagent. This is demonstrated in gram-scale synthesis including building blocks for materials chemistry and pharmaceutical industry. Furthermore, the direct coupling of aryllithiums as well as Grignard reagents with aryl chlorides was also easily accomplished at room temperature.

A diamino-substituted carbodiphosphorane as strong C-donor and weak N-donor: isolation of monomeric trigonal-planar L·ZnCl2.

The isolation, structural characterization and coordination chemistry of a di(amino)-substituted carbodiphosphorane (CDP) are reported. Compared to the analogue, dianionic bis(iminophosphoryl)methandiides, the CDP is a stronger C-, but much weaker N-donor which led to the isolation of solely C-coordinated metal complexes amongst an unusual monomeric trigonal-planar L·ZnCl2 complex.

Unraveling the High Activity of Ylide-Functionalized Phosphines in Palladium-Catalyzed Amination Reactions: A Comparative Study with CyJohnPhos and PtBu3.

Comprehensive mechanistic insights into the activity of different catalysts based on different ligands are important for further ligand design and catalyst improvement. Herein, we report a combined computational and experimental study on the mechanism and catalytic activity of the ylide-substituted phosphine Cy3P-C(Me)PCy2 (keYPhos, L1) in C-N coupling reactions including a comparison with the established and often-applied phosphines CyJohnPhos (L2) and P(tBu)3 (L3). Density functional theory (DFT) calculations together with the possible isolation of several intermediates within the catalytic cycle demonstrate that L1 readily forms low-coordinated palladium complexes [such as L1·Pd(dba)], which easily undergo oxidative addition and subsequent amine coordination as well as reductive elimination. Due to the possible opening and closing of the P-C-P angle in L1, the steric bulk can be adjusted to the metal environment so that L1 retains its conformation throughout the whole catalytic cycle, thus leading to fast catalysis at room temperature. Comparative studies of the three ligands with Pd2dba3 as a Pd source show that only L1 efficiently allows for the coupling of aryl chlorides at room temperature. DFT studies suggest that this is mainly due to the reluctance/inability of L2 and L3 to form the catalytically active species under these reaction conditions. In contrast, the YPhos ligand readily forms the prereactive complex and undergoes the first oxidative addition reaction. These observations are confirmed by kinetic studies, which indicate a short induction period for the formation of the catalytically active species of L1, followed by fast catalysis. This behavior of L1 is due to its unique electronic and steric properties, which support low activation barriers and fast catalyst generation.

Palladium Complexes Based on Ylide-Functionalized Phosphines (YPhos): Broadly Applicable High-Performance Precatalysts for the Amination of Aryl Halides at Room Temperature.

Palladium allyl, cinnamyl, and indenyl complexes with the ylide-substituted phosphines Cy3 P+ -C- (R)PCy2 (with R=Me (L1) or Ph (L2)) and Cy3 P+ -C- (Me)PtBu2 (L3) were prepared and applied as defined precatalysts in C-N coupling reactions. The complexes are highly active in the amination of 4-chlorotoluene with a series of different amines. Higher yields were observed with the precatalysts in comparison to the in situ generated catalysts. Changes in the ligand structures allowed for improved selectivities by shutting down ß-hydride elimination or diarylation reactions. Particularly, the complexes based on L2 (joYPhos) revealed to be universal precatalysts for various amines and aryl halides. Full conversions to the desired products are reached mostly within 1 h reaction time at room temperature, thus making L2 to one of the most efficient ligands in C-N coupling reactions. The applicability of the catalysts was demonstrated for aryl chlorides, bromides and iodides together with primary and secondary aryl and alkyl amines, including gram-scale applications also with low catalyst loadings of down to 0.05 mol %. Kinetic studies further demonstrated the outstanding activity of the precatalysts with TOF over 10.000 h-1 .

Ylide-Functionalized Phosphine (YPhos)-Palladium Catalysts: Selective Monoarylation of Alkyl Ketones with Aryl Chlorides.

Ylide-functionalized phosphine (YPhos) ligands allow the palladium-catalyzed α-arylation of alkyl ketones with aryl chlorides with record setting activity. Using a cyclohexyl-substituted YPhos ligand, a wide range of challenging ketone substrates was efficiently and selectively monoarylated under mild conditions. A newly designed YPhos ligand bearing tert-butyl groups on the coordinating phosphorus atom is already active at room temperature. The synthetic potential was demonstrated by gram-scale reactions and the succinct synthesis of ε-caprolactone derivatives.

Group 9 and 10 Metal Complexes of an Ylide-Substituted Phosphine: Coordination versus Cyclometalation and Oxidative Addition.

Ylide-substituted phosphines (YPhos) have been shown to be excellent ligands for several transition metal catalyzed reactions. Investigations of the coordination behavior of the YPhos ligand YSPPh2 (1) [with YS = (Ph3P)(SO2Tol)C] toward group 9 and 10 metals revealed a surprisingly diverse coordination chemistry of the ligand. With Ni(CO)4, the formation of a di- as well as tricarbonyl complex is observed depending on the reaction conditions. In [( κP,η 2 -benzene-1)Ni(CO)2] the phosphine ligand also coordinates via a phosphonium bound phenyl group to the metal leading to a unique nickel η 2 -arene interaction, which can be viewed as an intermediate state toward P-C bond activation. Full cleavage of the P-C bond takes place with [Rh(COD)Cl]2 leading to a complex salt with [( κP,κO-1)Rh(COD)]+ as cation and a dirhodium trichloride complex anion. Here, YSPPh2 underwent P-C bond cleavage to thus act as an anionic diphosphine ligand. In contrast, in [( κP,κO-1)Rh(COD)]+ as well as [( κP,κO-1)Rh(CO)Cl], formed from the reaction of 1 with [Rh(CO)2Cl]2, the YPhos ligand acts as bidentate ligand complexing the metal via the phosphine and sulfonyl moiety with an intact PPh3 unit. A further type of coordination is observed with [Ir(COD)Cl]2. Here, phosphine coordination is accompanied by C-H activation at one of the phosphonium bound phenyl groups leading to a cyclometalated complex.

Ylide-Functionalization via Metalated Ylides: Synthesis and Structural Properties.

The α-metallated ylides [Ph3P-C-Z]-M+ (with Z=SO2Tol or CN and M=Na or K) were used as versatile nucleophiles for the facile access to ylide-substituted compounds. Halogenations, alkylations, carbonylations and functionalization reactions with main group element halides were easily accomplished by simple trapping reactions with the appropriate electrophiles. X-ray crystallographic studies of all compounds - including the first structures of α-fluorinated P-ylides - showed remarkable differences in the ylide backbone depending on the substituents. In the fluorinated compounds, a change from a fully planar to a pyramidalized ylidic carbon centre was observed despite the strongly anion-stabilizing ability of the yldiide substituent. π-Donation from the ylide substituent also resulted in geometric restrictions depending on the steric and electronic properties of the introduced substituents.

Isolation of a Diylide-Stabilized Stannylene and Germylene: Enhanced Donor Strength through Coplanar Lone Pair Alignment.

The preparation of the first stable diylide-substituted stannylene and germylene (Y2 E, with E=Ge, Sn and Y=[PPh3 -C-SO2 Tol]- ) is reported. The synthesis is easily accomplished in one step from the sulfonyl-substituted metalated ylide YNa and the corresponding ECl2 precursors. Y2 Ge and Y2 Sn exhibit unusual structures in the solid state and in solution, in which the three adjacent lone pairs in the C-E-C linkage are arranged coplanar to each other. As shown by DFT studies, this bonding situation is preferred over the typical π-donation from the ligands into the empty p-orbital at the metal due to the strong anion-stabilizing ability of the sulfonyl groups in the ylide backbone and their additional coordination to the metal. The alignment of the three lone pairs leads to a remarkable boost of the HOMO energy and thus of the donor strengths of the tetrylenes. Hence, Y2 Ge and Y2 Sn become stronger donors than their diamino or diaryl congeners and comparable to cyclic alkyl(amino)carbenes. First reactivity studies confirm the high reactivity of Y2 Ge and Y2 Sn, which for example undergo an intramolecular C-H activation reaction via metal-ligand cooperation.

Isolation of the Metalated Ylides [Ph3 P-C-CN]M (M=Li, Na, K): Influence of the Metal Ion on the Structure and Bonding Situation.

The isolation and structural characterization of the cyanido-substituted metalated ylides [Ph3 P-C-CN]M (1-M; M=Li, Na, K) are reported with lithium, sodium, and potassium as metal cations. In the solid-state, most different aggregates could be determined depending on the metal and additional Lewis bases. The crown-ether complexes of sodium (1-Na) and potassium (1-K) exhibited different structures, with sodium preferring coordination to the nitrogen end, whereas potassium binds in an unusual η2 -coordination mode to the two central carbon atoms. The formation of the yldiide was accompanied by structural changes leading to shorter C-C and longer C-N bonds. This could be attributed to the delocalization of the free electron pairs at the carbon atom into the antibonding orbitals of the CN moiety, which was confirmed by IR spectroscopy and computational studies. Detailed density functional theory calculations show that the changes in the structure and the bonding situation were most pronounced in the lithium compounds due to the higher covalency.

A Highly Active Ylide-Functionalized Phosphine for Palladium-Catalyzed Aminations of Aryl Chlorides.

Ylide-functionalized phosphine ligands (YPhos) were rationally designed to fit the requirements of Buchwald-Hartwig aminations at room temperature. This ligand class combines a strong electron-donating ability comparable to NHC ligands with high steric demand similar to biaryl phosphines. The active Pd species are stabilized by agostic C-H⋅⋅⋅Pd rather than by Pd-arene interactions. The practical advantage of YPhos ligands arises from their easy and scalable synthesis from widely available, inexpensive starting materials. Benchmark studies showed that YPhos-Pd complexes are superior to the best-known phosphine ligands in room-temperature aminations of aryl chlorides. The utility of the catalysts was demonstrated by the synthesis of various arylamines in high yields within short reaction times.

Ylide-Functionalized Phosphines: Strong Donor Ligands for Homogeneous Catalysis.

Phosphines are important ligands in homogenous catalysis and have been crucial for many advances, such as in cross-coupling, hydrofunctionalization, or hydrogenation reactions. Herein we report the synthesis and application of a novel class of phosphines bearing ylide substituents. These phosphines are easily accessible via different synthetic routes from commercially available starting materials. Owing to the extra donation from the ylide group to the phosphorus center the ligands are unusually electron-rich and can thus function as strong electron donors. The donor capacity surpasses that of commonly used phosphines and carbenes and can easily be tuned by changing the substitution pattern at the ylidic carbon atom. The huge potential of ylide-functionalized phosphines in catalysis is demonstrated by their use in gold catalysis. Excellent performance at low catalyst loadings under mild reaction conditions is thus seen in different types of transformations.

Using Ylide Functionalization to Stabilize Boron Cations.

The metalated ylide YNa [Y=(Ph3 PCSO2 Tol)- ] was employed as X,L-donor ligand for the preparation of a series of boron cations. Treatment of the bis-ylide functionalized borane Y2 BH with different trityl salts or B(C6 F5 )3 for hydride abstraction readily results in the formation of the bis-ylide functionalized boron cation [Y-B-Y]+ (2). The high donor capacity of the ylide ligands allowed the isolation of the cationic species and its characterization in solution as well as in solid state. DFT calculations demonstrate that the cation is efficiently stabilized through electrostatic effects as well as π-donation from the ylide ligands, which results in its high stability. Despite the high stability of 2 [Y-B-Y]+ serves as viable source for the preparation of further borenium cations of type Y2 B+ ←LB by addition of Lewis bases such as amines and amides. Primary and secondary amines react to tris(amino)boranes via N-H activation across the B-C bond.

Bridging the Gap between Bisylides and Methandiides: Isolation, Reactivity, and Electronic Structure of an Yldiide.

Bisylides and methandiides are two unique families of carbon bases that have found a variety of applications in recent years. Metalated ylides (yldiides) are the link between these types of compounds. Yet, only little is known about their properties, reactivities, and particularly their electronic structure. Here, we report the preparation of the metalated ylide [Ph3P-C-SO2Tol](-) (1) with different alkali metal counterions. The compounds have been studied by X-ray diffraction analysis and NMR spectroscopy and the first structures of a sodium and potassium yldiide are presented. The electronic structure of 1 was explored by DFT calculations confirming its relation with other divalent carbon species. Reactivity studies demonstrate the strong nucleophilicity of the yldiide and its capability to act both as a σ- and π-donor.