In this account, the design, synthesis, and application of P‐chirogenic phosphine ligands that have been mainly carried out in our laboratory over the last three decades are described. Various ...enantiopure P‐chirogenic phosphine ligands have been efficiently prepared by using phosphine boranes as intermediates. Conformationally rigid and electron‐rich P‐chirogenic phosphine ligands possessing C2 symmetry as well as a bulky alkyl group and a small group at the phosphorus atoms exhibit excellent enantioselectivities and catalytic efficiency in a variety of transition‐metal‐catalyzed asymmetric reactions. Enantiopure 2,3‐bis(tert‐butylmethylphosphino)quinoxaline (QuinoxP*) is an air‐stable crystalline solid that shows superior enantioinduction ability in catalytic asymmetric syntheses. Mechanistic studies of Rh‐catalyzed asymmetric hydrogenation using structurally simple P‐chirogenic phosphine ligands, such as tBu‐BisP*, are briefly described.
Ligands on a large scale: Enantiopure P‐chirogenic phosphine ligands are efficiently prepared via phosphine boranes. Conformationally rigid and electron‐rich P‐chirogenic phosphine ligands, with a bulky alkyl group and a small group at the phosphorus atoms, exhibit excellent enantioselectivities in various metal‐catalyzed asymmetric reactions. These ligands are also used in the mechanistic study of Rh‐catalyzed asymmetric hydrogenation.
Metal-catalyzed asymmetric synthesis is one of the most important methods for the economical and environmentally benign production of useful optically active compounds. The success of the asymmetric ...transformations is significantly dependent on the structure and electronic properties of the chiral ligands coordinating to the center metals, and hence the development of highly efficient ligands, especially chiral phosphine ligands, has long been an important research subject in this field. This review article describes the synthesis and applications of P-chiral phosphine ligands possessing chiral centers at the phosphorus atoms. Rationally designed P-chiral phosphine ligands are synthesized by the use of phosphine–boranes as the intermediates. Conformationally rigid and electron-rich P-chiral phosphine ligands exhibit excellent enantioselectivity and high catalytic activity in various transition-metal-catalyzed asymmetric reactions. Recent mechanistic studies of rhodium-catalyzed asymmetric hydrogenation are also described.
Finding optimal chiral ligands for transition-metal-catalyzed asymmetric reactions using trial-and-error methods is often time-consuming and costly, even if the details of the reaction mechanism are ...already known. Although modern computational analyses allow the prediction of the stereoselectivity, there are only very few examples for the attempted design of chiral ligands using a computational approach for the improvement of the stereoselectivity. Herein, we report a systematic method for the design of chiral ligands for the enantioselective Markovnikov hydroboration of aliphatic terminal alkenes based on a computational and experimental evaluation sequence. We developed a three-hindered-quadrant P-chirogenic bisphosphine ligand that was designed in accordance with the design guidelines derived from this method, which allowed the Markovnikov hydroboration to proceed with high enantioselectivity (up to 99% ee).
A new series of C 1-symmetric P-chirogenic bisphosphine ligands of the type (R)-5,8-Si-Quinox-tBu3 (Silyl = SiMe3, SiEt3, SiMe2Ph) have been developed. The bulky silyl modulators attached to the ...ligand backbone fix the phosphine substituents to form rigid chiral environments that can be used for substrate recognition. The ligand showed high performances for a copper(I)-catalyzed asymmetric borylative cyclopropanation of bulky silyl-substituted allylic electrophiles to afford higher disfavored 1,2-cis-silyl-boryl-cyclopropanes than the other possible isomers, trans-cyclopropane and allylboronate (up to 97% yield; 98% ee; cis/trans = >99:1; cyclopropane/allylboronate = >99:1). Detailed computational studies suggested that the highly rigid phosphine conformation, which is virtually undisturbed by the steric interactions with the bulky silyl-substituted allyl electrophiles, is key to the high stereo- and product-selectivities. Furthermore, the detailed computational analysis provided insight into the mechanism of the stereoretention or -inversion of the chiral alkylcopper(I) intermediate in the intramolecular cyclization.
A bulky three-hindered quadrant bisphosphine ligand, di-1-adamantylphosphino(tert-butylmethylphosphino)methane, named BulkyP*, has been synthesized via a convergent short pathway with ...chromatography-free procedures. The ligand is a crystalline solid and can be readily handled in air. Its rhodium(I) complex exhibits very high enantioselectivities and catalytic activities in the asymmetric hydrogenation of functionalized alkenes.
The first copper(I)‐catalyzed enantioselective borylation of racemic benzyl chlorides has been realized by a quadrant‐by‐quadrant structure modulation of QuinoxP*‐type bisphosphine ligands. This ...reaction converts racemic mixtures of secondary benzyl chlorides into the corresponding chiral benzylboronates with high enantioselectivity (up to 92 % ee). The results of mechanistic studies suggest the formation of a benzylic radical intermediate. The results of DFT calculations indicate that the optimal bisphosphine‐copper(I) catalyst engages in noncovalent interactions that efficiently recognize the radical intermediate, and leads to high levels of enantioselectivity.
Radical recognition: The copper(I)‐chiral phosphine ligand catalyst developed by the elaborate quadrant‐by‐quadrant structure modulation of the ligand enabled an asymmetric borylation of benzyl chlorides. Noncovalent interactions, such as C−H/π and C−H/O interactions, are essential for the enantioselective recognition of the radical intermediate.
A new P-chiral phosphine ligand, (R,R)-2,3-bis(tert-butylmethylphosphino)quinoxaline, has been prepared by the reaction of enantiomerically pure tert-butylmethylphosphine−borane with ...2,3-dichloroquinoxaline. This ligand, in contrast to most of the previously reported P-chiral ligands, is an air-stable solid and exhibits excellent enantioselectivities in both Rh-catalyzed asymmetric hydrogenations and Rh- or Pd-catalyzed carbon−carbon bond-forming reactions.
Novel P-stereogenic PCP pincer–Pd complexes were designed and prepared in short steps from optically pure tert-butylmethylphosphine-borane. These optically active Pd-complexes were successfully ...applied in asymmetric addition of diarylphosphines to nitroalkenes with high yields and good enantioselectivity.
A Pd-catalyzed asymmetric allylic substitution with 1,3-dithianes as acyl anion equivalents has been developed in high yields and excellent enantioselectivities. The reaction was performed on a gram ...scale, and the corresponding alkylated products were conveniently converted into several biologically active products. This work provides an alternative strategy utilizing electrophilic carbonyl compounds as nucleophilic species in a Pd-catalyzed allylic substitution.
Asymmetric hydrogenation of sterically hindered substrates still constitutes a long-standing challenge in the area of asymmetric catalysis. Herein, an efficient palladium acetate (an inexpensive Pd ...salt with low toxicity) catalyzed asymmetric hydrogenation of sterically hindered N-tosylimines is realized with high catalytic activities (S/C up to 5000) and excellent enantioselectivities (ee up to 99.9%). Quantum chemical calculations suggest that uniformly high enantioselectivities are observed due to the structurally different S- and R-reaction pathways.
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