Novel Synthesis of Chiral 1,3-Diphosphines via Palladium Template Promoted Hydrophosphination and Functional Group Transformation Reactions

Abstract

A novel cyano-functionalized monophosphine palladium substrate containing the ortho-metalated (R)-(1-(dimethylamino)ethyl)naphthalene as the chiral auxiliary was synthesized from 3-chloropropionaldehyde diethylacetal via a one-pot process. The asymmetric hydrophosphination reactions between diphenylphosphine and the trans-or cis-monophosphine substrates were carried out under mild conditions, which gave the corresponding cyano-substituted chiral 1,3-bis(diphenylphosphino)propane palladium complexes with good yields and stereoselectivities. Subsequent functional group transformation reactions were conducted by successive treatment of the hydrophosphination products with Dibal-H and chemoselectively yielded the formyl-and hydroxyl-functionalized chiral 1,3-diphosphine complexes. The absolute configurations and coordination information of the novel 1,3-diphosphine complexes were analyzed by X-ray crystallography. The optically pure 1,3-bis-(diphenylphosphino)propane ligands with cyano, formyl, and hydroxyl functionalities could be liberated in high yields from the corresponding dihalo palladium complexes by treatment with aqueous potassium cyanide.

Broken Promises? On the Continued Challenges Faced in Catalytic Hydrophosphination

“…In principle, asymmetric HP is an incredibly powerful synthetic route to access the next generation of chiral phosphine ligands. This area of HP has been dominated by palladium complexes bearing chiral chelating auxiliaries. − However, there have been early examples of nickel-catalyzed , and organocatalytic − asymmetric HP. More recently Wang and co-workers reported the asymmetric HP of numerous azabenzonorbornadiene and oxabenzonorbornadiene substrates with different secondary biarylphosphines mediated by palladium precatalyst and Fe­(OAc) 2 as a substoichiometric additive (Scheme ).…”

Insertion Reactions and Catalytic Hydrophosphination of Heterocumulenes using α-Metalated N,N-Dimethylbenzylamine Rare-Earth-Metal Complexes

“…The effective catalysis of hydroamination, − hydrosilylation, − and hydrophosphination − is very attractive, due to the 100% atom economy involved in these reactions . In contrast to the myriad reported catalysts for hydroamination and hydrosilylation reactions, the number of known hydrophosphination catalysts remains small, although they span the entire periodic table, with several reports involving late transition metals. ,− Early-metal catalysts, such as those of Waterman and Mindiola, have been utilized in the intermolecular hydrophosphination of alkynes. , Main-group metals can also be effective, as noted in Cui, Stephan, and Hill’s reports on alkali-metal- and alkaline-earth-metal-catalyzed hydrophosphination reactions. ,, Furthermore, the Marks and Hou groups have shown that even f elements can be employed, as demonstrated in the hydrophosphination of olefins and carbodiimides using constrained-geometry lanthanide catalysts. , We were especially intrigued by the use of lanthanides, due to the various possible advantages available with these metals, such as their electrophilicities, the ability to tune the steric environment about these metal centers through a proper choice of supporting ligands, and their absence of unproductive oxidative addition/reductive elimination reaction pathways.…”

Asymmetric synthesis of functionalized chiral diphosphines via organopalladium promoted hydrophosphination and diels-alder reactions

“…Asymmetric hydrogenation, by employing the clean molecular hydrogen to reduce the prochiral C=C, C=O, and C=N double bonds, is probably one of the most simplest and powerful method to produce a myriad of chiral amino acid derivatives, chiral alcohols, and chiral amines, which are important building blocks for organic synthesis. 4,5 The pioneer work was presented in 1971 by Kagan, 6 who developed the first chiral diphosphine ligand, DIOP, derived from tartaric acid, for rhodium-catalized asymmetric hydrogenation reactions with high enantioselectivities. Knowles made his significant contribution by discover a P-chiral diphosphine, DIPAMP, in 1975.…”

“…is smaller than its counterpart in complex 37a, resulting in a relative larger bite angle (85.1(1)°), and the angles around the metal center are in the ranges of of 80.5(1) -99.8 (1) and 174.4(1) -178. 4(1)°. The newly formed stereogenic center at C27 adopts the S absolute configuration with the keto functionality occupying the sterically favorable equatorial position.…”

“…The design and synthesis of new chiral phosphine ligands continues to be a research topic of great interest in modern organophosphorus chemistry, since the enantiomerically pure phosphines have established their position as highly effective ligands in transition metal catalyzed asymmetric reactions on both research laboratory and industrial scales. 4,5 It is conceivable that the presence of proper functional groups, for instance hydroxyl, amino, or ester on chiral phosphine frameworks can efficiently improve both reactivity and enantioselectivity in many reactions through the secondary interactions with the reacting substrates. 97 Over the past few years, our group has successfully prepared a series of functionalized chiral phosphine ligands by means of asymmetric hydrophosphination 67,79 and Diels-Alder reactions, 66 (2) By tuning the chloro ligand that is trans to the naphthalene carbon, it can alternatively provide one or two distinct coordination sites around the square planar palladium center to selectively synthesize functionalized mono-or bidentate phosphine ligands.…”