Conspectus

Given the important influence of phosphine ligands in transition metal-catalyzed reactions, chemists have searched for straightforward and efficient methodologies for the synthesis of diverse phosphine ligands. Although significant progress has been made in this aspect over the past decades, the development of new phosphorus-containing ligands with properties superior to their predecessors remains a central task for chemists. Recently, researchers have demonstrated that biphenyl monophosphine ligands function as highly efficient ligands for transition-metal-catalyzed organic transformations, especially for reactions where chelating bisphosphine ligands cannot be used. In 1998, Buchwald introduced a new class of air-stable phosphine ligands based on the dialkylbiaryl phosphine backbone. These ligands have been successfully used for a wide variety of palladium-catalyzed carbon–carbon, carbon–nitrogen, and carbon–oxygen construction processes as well as serving as supporting ligands for a number of other reactions. At the same time, the use of the biphenyl monophosphine ligands often allows reactions to proceed with short reaction times and low catalyst loadings and under mild reaction conditions. However, the synthesis of chiral biphenyl monophosphine ligands, especially those the chirality of which is due to biaryl axial chirality, is very limited.

In this Account, we summarize our methodologies for the synthesis of this kind of biphenyl monophosphine ligands including the P═O directed C–H functionalization, P═O directed diastereoselective C–H functionalization, P═O directed enantioselective C–H functionalization, and metal-free diastereoselective radical oxidative C–H amination under mild reaction conditions. With these methods, a series of biphenyl phosphine ligand precursors containing achiral or axially chiral centers and precursors possessing both axial chirality and a chirogenic phosphorus center with different electronic properties and steric effect have been obtained under different reaction conditions. For the preparation of chiral biphenyl monophosphine ligands, which not only possess axial chirality but in many cases also possess chirality at phosphorus, the primary means of introducing chirality is through the use of the menthyl phenylphosphinate. As a chiral auxiliary group, the menthyl phenylphosphinate has some unique features: (i) it is easy to prepare; (ii) the products contain both axial chirality and central chirality on the phosphorus atom; (iii) the menthyl group could easily be transformed into other functional groups, which is crucial for the diversity of the corresponding biphenyl ligands. In our reaction, the P═O group not only acts as the directing group but also facilitates the construction of the phosphine ligands. In addition, the application of these products in asymmetric catalysis has also been studied with good results obtained in some reactions. The further application of these ligands, especially the chiral biphenyl monophosphine ligands in catalysis reactions is underway in our laboratory, and we hope different kinds of reactions will be achieved with these ligands.