Organolithium chemistry! An overview of the structure formation principles and the strong structure–reactivity relationship of lithium organics is given. By means of the commonly used lithium bases ...the deaggregation of the oligomeric parent structures to small adducts is presented (see examples) and compared to the related chemistry of lithiosilanes.
The structure–reactivity relationship is an important feature of organolithium compounds. The knowledge of the structure of reactive species is crucial for the elucidation of reaction mechanisms and the understanding of observed selectivities. This concept article gives an overview over the structural principles of lithium organics and their Lewis base coordinated complexes in the solid state. The transition from the oligomeric parent structures to smaller adducts, such as dimers and monomers, as well as special degrees of aggregation is presented. Besides the commonly used alkyllithium compounds, a short overview over the structural principles of the higher homologous silyllithium compounds is given. Moreover, the structure–reactivity relationship is depicted by means of the reactivity of the Lewis bases towards intramolecular decomposition reactions with the organolithium compound. Selected examples confirm the importance of structure elucidation for the understanding of mechanistic pathways and selectivities.
Organolithium chemistry! An overview of the structure formation principles and the strong structure–reactivity relationship of lithium organics is given. By means of the commonly used lithium bases the deaggregation of the oligomeric parent structures to small adducts is presented (see examples) and compared to the related chemistry of lithiosilanes.
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.
Give a little bit: The ylide‐functionalized phosphine CyYMePCy2, which is easy to synthesize in few steps, shows excellent performance in a series of C−N cross coupling reactions at room temperature. This efficiency can be explained by the strong electron‐donating properties of the ligand and its unique architecture, which allows stabilization of the active Pd species through a weak C−H⋅⋅⋅Pd interaction.
Palladium allyl, cinnamyl, and indenyl complexes with the ylide‐substituted phosphines Cy3P+−C−(R)PCy2 (with R=Me (L1) or Ph (L2)) and Cy3P+−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 β‐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.
User‐friendly and easily accessible Pd complexes of three ylide‐substituted phosphines (YPhos) were prepared and applied in C−N coupling reactions giving way to extremely active catalysts that allow for high yields and selectivities at room temperature for a wide variety of substrates. Aryl chlorides, bromides, and iodides were successfully coupled also in gram‐scale and with low catalyst loadings including difficult substrates, such as alkyl amines.
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.
YPhos: The ylide‐functionalized phosphines (YPhos), a novel class of strong donor ligands, are readily accessible from commercially available starting materials and exhibit easily tunable electronic and steric properties. The huge potential of these ligands in catalysis is demonstrated by their use in gold catalysis, with excellent performance observed at low catalyst loadings under mild reaction conditions.
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 Y
Mes
PCy
2
, 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.
Modification of the backbone in ylide-substituted phosphines allowed a remarkable boost in the catalytic activity, thus enabling a series of gold catalyzed transformations at very low catalyst loadings.
The metalated ylide YNa Y=(Ph3PCSO2Tol)− was employed as X,L‐donor ligand for the preparation of a series of boron cations. Treatment of the bis‐ylide functionalized borane Y2BH with different trityl ...salts or B(C6F5)3 for hydride ion 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 Y2B+←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.
Ylide meets B+: Employing a metalated ylide as donor ligand makes possible the isolation of highly stable ylide‐functionalized boron cations. π‐Delocalization as well as electrostatic interactions within the C−B−C linkage play the most important role for the high stability of the Y−B−Y+ cation and its Lewis base adducts. Reaction with amines results in N−H activation by addition across the B−C bond.
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 (PhYPhos) or PCy3 (CyYPhos) 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 PhYPhos and CyYPhos 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.
Experimental and computational studies on PPh3 and PCy3‐substituted ylide‐functionalized phosphines as well as on a biaryl and a cyclohexyl‐aryl phosphine demonstrate that Au⋅⋅⋅H−C hydrogen bonds can serve as secondary metal ligand interactions similar to gold–arene interactions often used in ligand design for the stabilization of catalytically active species. Remarkably short Au−H bonds are observed.
Catnip craze: Nepetalactone, the psychoactive ingredient of catmint, was selected as starting material for the first enantioselective synthesis of englerin A. This cytotoxic guaiane sesquiterpene is ...a highly selective inhibitor (1–87 nM) of several renal cancer cell lines. The absolute configuration of this natural product was determined by total synthesis.
The synthesis of a ruthenium carbene complex based on a sulfonyl‐substituted methandiide and its application in bond activation reactions and cooperative catalysis is reported. In the complex, the ...metal–carbon interaction can be tuned between a RuC single bond with additional electrostatic interactions and a RuC double bond, thus allowing the control of the stability and reactivity of the complex. Hence, activation of polar and non‐polar bonds (OH, HH) as well as dehydrogenation reactions become possible. In these reactions the carbene acts as a non‐innocent ligand supporting the bond activation as nucleophilic center in the 1,2‐addition across the metal–carbon double bond. This metal–ligand cooperativity can be applied in the catalytic transfer hydrogenation for the reduction of ketones. This concept opens new ways for the application of carbene complexes in catalysis.
Not so innocent after all: The synthesis of methandiide‐based ruthenium carbene complexes and their application in bond activation reactions is reported. Depending on the co‐ligands, the metal–carbon interaction can be tuned to control reactivity and thus bond activation and dehydrogenation reactions. Thereby, the carbene acts as a non‐innocent ligand supporting these reactions as nucleophilic center. This cooperation can be applied in transfer hydrogenation, thus opening new ways for the application of carbene complexes.
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