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.

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 ylidesubstituted phosphine Cy 3 P−C(Me)PCy 2 (keYPhos, L1) in C−N coupling reactions including a comparison with the established and often-applied phosphines Cy JohnPhos (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 Pd 2 dba 3 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.

Ylide-functionalized phosphine (YPhos) ligands allow the palladium-catalyzed α-arylation of alkyl ketones with aryl chlorides with record setting activity. Using a cyclohexylsubstituted 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 εcaprolactone derivatives.

Organolithium compounds are amongst the most important organometallic reagents and frequently used in difficult metallation reactions.H owever,t heir direct use in the formation of C À Cbonds is less established. Although remarkable advances in the coupling of aryllithium compounds have been achieved, Csp 2 ÀCsp 3 coupling reactions are very limited. Herein, we report the first general protocol for the coupling or aryl chlorides with alkyllithium reagents.P alladium catalysts based on ylide-substituted phosphines (YPhos) were found to be excellently suited for this transformation giving high selectivities at room temperature with avariety 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.

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.