Versatile Chiral Bidentate Ligands Derived from α-Amino Acids:  Synthetic Applications and Mechanistic Considerations in the Palladium-Mediated Asymmetric Allylic Substitutions

Abstract

A new class of chiral amidine-phosphine hybrid ligands 7a,b, which are readily accessible from the corresponding alpha-amino acids, were developed. A versatility for construction of new ligands is desirable, by which a variety of reactions and substrates become applicable. Indeed, a variety of modifications, such as exchange reactions to other amino groups in the amidine skeleton and the production of other types of ligands, are possible using the precursor compounds of 7a. Thus, novel chiral ligands 7c,d, 8, 11, and 13, which provide sterically and electronically different chiral circumstances, were prepared and used for the palladium-mediated asymmetric allylic substitutions of both acyclic and cyclic compounds. In these reactions, high levels of asymmetric induction were achieved for both substrates. A marked advancement of reactivity and enantioselectivity in palladium-catalyzed asymmetric allylations of 1,3-diphenylpropen-2-yl pivalate 14a was attained by examination of electronic substituent effects in a new series of chiral P-N and S-N hybrid ligands 8 and 11. Mechanistic views concerning the enantiodiscriminating step were demonstrated, in which a good correlation between a novel Pr/Mr concept and the absolute configuration of allylation products are discussed for the prediction of enantioselecting direction. The use of ketene silyl acetals as nucleophiles was investigated and compared with the corresponding harder anionic carbon nucleophiles. The former nucleophiles afforded higher enantioselectivity in asymmetric allylic transformations of 14a.

Preparation of Axially Chiral Biphenyl Diphosphine Ligands and Their Application in Asymmetric Hydrogenation

“…We first proposed a P/M chirality concept, 24) where the positioning array of four phenyl rings of diphosphine ligands closely correlates with the absolute configuration of products in asymmetric hydrogenation, and later presented a more general concept, Pr/Mr chirality, 25) for showing all chiral bidentate ligands (e.g. P,P-ligand, P,N-ligand, S,N-ligand, N,N-ligand, etc.)…”

Preparation of Enantiopure Norbornane Ligands Bearing Both (2S,3S)-Bis(phosphinomethyl) and 7-syn-Oxygen Functional Groups and an Application to Rhodium-Catalyzed Asymmetric Hydrogenation

“…We previously reported the correlation between the chirality of bidentate ligands and the absolute configuration of the products obtained by rhodium-catalyzed asymmetric hydrogenation or palladium-catalyzed asymmetric allylic alkylation. We first proposed a P/M chirality concept, 11) where the positioning array of four phenyl rings of diphosphine ligands closely cor- relates with the absolute configuration of products in asymmetric hydrogenation, and later represented a more general concept, Pr/Mr chirality, 12) for showing all chiral bidentate ligands (e.g, P,N-ligand, S,N-ligand, N,N-ligand, etc.) (Chart 3).…”

Chiral ferrocene-based phosphine-imine and sulfur-imine ligands for palladium-catalyzed asymmetric allylic alkylation of cycloalkenyl esters

“…To this Pd-catalyst was added cycloalkenyl esters 5 (0.50 mmol) in toluene (1.5 ml), followed by dimethyl malonate (170 ul, 1.5 mmol) or diethyl methylmalonate (260 ul, 1.5 mmol), N,O-bis(trimethylsilyl)acetamide (BSA, 0.37 ml, 1.5 mmol), and a catalytic amount of LiOAc (0.01 mmol) sequentially. After stirring for 24 h at room temperature, the reaction mixture was quenched with saturated aqueous NH 4 Cl solution and diluted with CH 2 Cl 2 . The organic layer was separated, dried over MgSO 4 , and concentrated under reduced pressure.…”

“…With the aim of meeting the above-mentioned requirements, a small quantity of diphosphine, phosphine-oxazoline, and phosphorus-sulfur ligands have been designed and applied in this reaction with good enantioselectivity recently (for examples of Pdcatalyzed asymmetric allylic alkylation of cycloalkenyl substrates, see: [3]). To the best of our knowledge, however, there are few report on the easily prepared and modified phosphine-Schiff base imine ligands for Pd-catalyzed asymmetric allylic alkylation of cycloalkenyl esters and no claim of the good enantioselectivity obtained with this kind of ligands [4], although very high enantioselectivity have been achieved in Pd-catalyzed alkylation of 1,3-diphenylprop-2-en-1-yl acetate with them (for examples of phosphine-imine ligands for Pd-catalyzed asymmetric allylic alkylation of 1,3-diphenylprop-2-en-1-yl esters, see: [5]). In the course of our work in the field of asymmetric synthesis [6], we have reported a series of readily accessible ferrocenebased phosphine-imine ligands 1-2 by the reaction of (R)-…”