Asymmetric Suzuki-Miyaura Coupling Reactions Research Articles

Palladium/Azaphos-Catalyzed Asymmetric Suzuki–Miyaura Coupling

AbstractA palladium-catalyzed asymmetric Suzuki–Miyaura coupling is described with a unique monophosphine ligand, Azaphos. This method provides a new ligand framework that could be used in asymmetric Suzuki–Miyaura coupling reactions to prepare the axially chiral compounds.

A General Catalyst Controlled Route to Prostaglandin F2α.

We report a general, catalyst-controlled route to prostaglandin F2α and its analogues. The approach uses a Rh-catalyzed dynamic kinetic asymmetric Suzuki-Miyaura coupling reaction between a racemic bicyclic allyl chloride and alkenyl boronic esters bearing chiral alcohols to give cyclopentyl intermediates bearing 3 contiguous stereocenters. The route provides advanced intermediates in 99% ee as a single diastereoisomer in all cases examined, with the absolute stereochemistry of the cyclopentane core controlled by the ligand. Intermediates that could be used to produce prostaglandin analogues such as bimatoprost, latanoprost, fluprostenol, and cloprostenol were synthesized. The final two stereocenters were installed via Pd-catalyzed Tsuji-Trost alkylation and iodolactonization. The synthesis of PG F2α was achieved in 19% yield in 16 longest linear steps.

Pd(II)-immobilized on a novel covalent imine framework (COF-BASU1) as an efficient catalyst for asymmetric Suzuki coupling

This study reports the synthesis of a new imine-based covalent organic framework (COF) stabilizer through the reaction between 1,4-phenylenediamine and 4,4′,4″-(benzene-1,3,5-triyltris(oxy))tribenzaldehyde (COF-BASU1). Next, palladium (Pd) species were decorated on the synthesized COF, and the obtained Pd/COF-BASU1 composite was used as a heterogeneous catalyst in the asymmetric Suzuki-Miyaura coupling (SMC) reaction. The easily prepared imine-linked COF-BASU1 possesses a two-dimensional eclipsed layered-sheet structure, making its incorporation with metal ions feasible. Via a simple post-treatment, a Pd(II)-containing COF, Pd/COF-BASU1, was accordingly synthesized, which showed excellent catalytic activity in catalyzing the asymmetric Suzuki-Miyaura coupling reaction with high stereoselectivity. The eclipsed imine structure provide chiral environment to achieve the asymmetric Suzuki-Miyaura coupling reactionplay. Afterward, the chiral high-performance liquid chromatography (HPLC) was conducted to examine the axially chiral products generated through these reactions. These products were separated via the HPLC method. This technique is based on the function of some columns whose packing groups can segregate chiral products. The fabricated nanocatalyst was structurally authenticated using various analytical techniques such as FT-IR, XRD, FE-SEM, TGA, EDS, ICP-AES, and BET. The outcomes indicated that Pd/COF-BASU1 nanocomposite is a suitable catalyst to synthesis axially chiral biaryl derivatives with high stereoselectivity (up to 85.37% ee).

Synthesis and Evaluation of Novel Planar‐Chiral Monophosphine Ligands Bearing Ferrocene‐Triazole Backbones

We prepared novel planar chiral monophosphine ligands bearing ferrocene-triazole backbones. These ligands were produced in a series of steps that included triazole synthesis by diastereoselective azidation and Huisgen cycloaddition of (S)-Ugi's amine, followed by methylation and phosphine introduction. This method was applicable to the preparation of various analogues due to the wide substrate scope of the Huisgen cycloaddition reaction. These ligands showed good catalytic activity in Suzuki–Miyaura coupling reactions, especially those involving bulky substrates. Furthermore, the optically active versions of these ligands were used in the asymmetric Suzuki–Miyaura coupling reaction to produce the axial chiral binaphthyl compound with moderate enantioselectivity. The ligand developed in this study is the first triazole-type biaryl- monophosphine ligand that can be used in asymmetric reactions, and it is expected to be a new tool for the accessing chiral compounds.

Pd-catalyzed asymmetric Suzuki-Miyaura coupling reactions for the synthesis of chiral biaryl compounds with a large steric substituent at the 2-position.

Pd-catalyzed asymmetric Suzuki–Miyaura couplings of 3-methyl-2-bromophenylamides, 3-methyl-2-bromo-1-nitrobenzene and 1-naphthaleneboronic acids have been successfully developed and the corresponding axially chiral biaryl compounds were obtained in very high yields (up to 99%) with good enantioselectivities (up to 88% ee) under mild conditions. The chiral-bridged biphenyl monophosphine ligands developed by our group exhibit significant superiority to the naphthyl counterpart MOP in both reactivity and enantioselectivity control. The large steric hindrance from π-conjugated ortho-substituents of the bromobenzene substrates and the Pd···O interaction between carbonyl and palladium seem essential to achieve high enantioselectivity.

Development of New Chiral Phosphine Ligands with Helical Environments and Their Application in Asymmetric Catalytic Reactions

The design and development of new chiral ligands to enable precise stereocontrol in a wide variety of reactions is one of the most important branches of organic synthesis. To date, the development of hybrid ligands containing both σ-donating and π-donating groups has attracted considerable attention, with unprecedented reactivities and stereoselectivities being observed. Therefore to develop efficient hybrid chiral ligands with novel structural motifs, we envisage that helicene would be a suitable π-donor efficiently to construct a helical environment around a metal center. In this context, we herein describe our recent efforts to develop a series of novel chiral [5]helicene-derived phosphine ligands (L1, with a 7,8-dihydro[5]helicene core structure, and L2, with a fully aromatic [5]helicene core structure). The prepared ligands, and in particular L1, were found highly effective in the asymmetric allylation of 1,3-diphenylallyl acetate with indoles and etherification with alcohols. Furthermore, in the asymmetric Suzuki-Miyaura coupling reaction, L2 exhibited excellent enantioselectivities. Finally, density functional theory studies were employed to propose a model that accounts for the origin of such high enantioselectivity in these reactions.

Synthesis of Chiral‐Bridged Atropisomeric Monophosphine Ligands with Tunable Dihedral Angles and their Applications in Asymmetric Suzuki–Miyaura Coupling Reactions

AbstractPrecise chiral recognition was firstly realized in the construction of diastereomeric biaryl monophosphines by means of the substrate‐directed asymmetric annulation reactions. A series of new chiral‐bridged atropisomeric biphenyl monophosphine ligands with tunable dihedral angles was accordingly synthesized successfully without a resolution step being needed. Using these ligands, different kinds of axially chiral 1,1′‐biaryl‐2‐phosphonates including the first reported quinolyl biaryl phosphonates were prepared in 42–97% yields with up to 96% ee via palladium‐catalyzed asymmetric Suzuki coupling reactions.magnified image

A Quantum-Chemical DFT Approach to Elucidation of the Chirality Transfer Mechanism of the Enantioselective Suzuki–Miyaura Cross-Coupling Reaction

The DFT calculations of the simplified model of the asymmetric Suzuki–Miyaura coupling reaction were performed at the M062x/LANL2DZ theory level at first. It was found that enantioselective reactions mediated by the palladium complexes of chiralC,P-ligands follow a four-stage mechanism similar to that proposed previously as one of the most credible mechanisms. It should be underlined that the presence of substituents in the substrates and the chiral ligand atorthopositions determines the energies of possible diastereoisomeric transition states and intermediates in initial reaction steps. This suggests that, in practice, a sharp selection of theoretically possible paths of chirality transfer from the catalyst to the product should have a place and, therefore, the absolute configuration of the formed atropisomeric product is defined and can be predicted.

Solvent Effect on the Sergeants-and-Soldiers Effect Leading to Bidirectional Induction of Single-Handed Helical Sense of Poly(quinoxaline-2,3-diyl)s Copolymers in Aromatic Solvents.

Random poly(quinoxaline-2,3-diyl) copolymers, containing chiral (S)-3-octyloxymethyl and achiral propoxymethyl side chain units, experience an abnormal sergeants-and-soldiers effect, that is, they adopt, depending on the chiral monomer mole fraction, either P- or M-helical conformations in anisole (PhOCH3) and benzotrifluoride (PhCF3). In benzene (PhH) and toluene (PhCH3), these copolymers exclusively adopt an M-helical conformation, regardless of the chiral monomer mole fraction. For a co-300mer, with a 40% mole fraction of chiral units, the selective induction of an M-helix (>99%) was observed in PhH, while in PhCF3, a P-helical conformation was induced selectively (>99%). This helix inversion of the polymer backbone is thus able to control the chirality of a chiral polymer ligand in aromatic solvents. The incorporation of a small amount of coordinating PPh2 groups into the copolymer resulted in a chiral macromolecular ligand, which allowed the enantioselective synthesis of both enantiomeric products in an asymmetric Suzuki-Miyaura coupling reaction (R-product: 91% ee in PhH; S-product: 95% ee in PhCF3) from a single catalyst.

Chiral linker-bridged bis-N-heterocyclic carbenes: design, synthesis, palladium complexes, and catalytic properties.

A series of chiral bis(benzimidazolium) salts 10-19 with (1R,2R)-cyclohexene, (1R,2R)-diphenylethylene and (aR)-binaphthylene linkers have been designed and synthesized in 30-94% yield. Ten chiral bis(NHC) palladium complexes 20-28 have been synthesized and characterized by NMR, HRMS, elemental analysis and further confirmed by X-ray single crystal analysis. These bis(NHC)-Pd complexes showed obviously different catalytic properties in the asymmetric Suzuki-Miyaura coupling reactions. The (1R,2R)-cyclohexene-bridged bis(NHC)-Pd complex, (R,R)-23, achieved the highest yield of 90%, while complex (aR)-28, with a binaphthylene linker, showed the best enantioselectivity of 60 ee%. The structural analysis of these complexes suggested that such difference of catalytic performance has a close relationship with their coordination surroundings around metal centres.

ChemInform Abstract: Palladium Catalyzed Asymmetric Suzuki—Miyaura Coupling Reactions to Axially Chiral Biaryl Compounds: Chiral Ligands and Recent Advances

AbstractReview: 69 refs.

Asymmetric Suzuki-Miyaura cross-coupling for the synthesis of chiral biaryl compounds as potential monophosphine ligands.

Efficient asymmetric Suzuki-Miyaura coupling reactions have been employed for the first time to synthesize chiral biaryl compounds with phosphinate groups as chiral auxiliaries. A series of functionalized chiral biaryls are thereby synthesized in excellent yields and good diastereoselectivities (up to >95:5 d.r.) and axially chiral monophosphorus ligands are obtained through further functionalizations.

Chiral PEPPSI Complexes: Synthesis, Characterization, and Application in Asymmetric Suzuki–Miyaura Coupling Reactions

PEPPSI complexes incorporating chiral N-heterocyclic carbene (NHC) ligands based on 2,2-dimethyl-1-(o-substituted aryl)propan-1-amines were synthesized. Two complexes, with one saturated and one unsaturated NHC ligand, were structurally characterized. The chiral PEPPSI complexes were used in asymmetric Suzuki–Miyaura reactions, giving atropisomeric biaryl products in modest to good enantiomeric ratios.

Chiral CNN Pincer Palladium(II) Complexes with 2-Aryl-6-(oxazolinyl)pyridine Ligands: Synthesis, Characterization, and Application to Enantioselective Allylation of Isatins and Suzuki–Miyaura Coupling Reaction

A series of chiral 2-aryl-6-(oxazolinyl)pyridine (aryl = phenyl or 1-naphthyl) ligands 2a–f were conveniently prepared from commercially available 6-bromo-2-picolinaldehyde in two steps. Reaction of 2a–f with PdCl2 in toluene in the presence of sodium bicarbonate afforded the corresponding CNN pincer Pd(II) complexes 3a–f via aryl C–H bond activation of the related ligands. All of the new compounds have been fully characterized by elemental analysis (MS for ligands), 1H and 13C NMR, and IR spectra. In addition, the molecular structures of Pd(II) complexes 3c–f have been determined by X-ray single-crystal diffraction. The obtained chiral pincer catalysts were successfully used in the asymmetric allylation of isatins with allyltributyltin, giving the corresponding 3-allyl-3-hydroxyoxindoles in high yields with enantioselectivities of up to 86% ee. These pincers could also catalyze the asymmetric Suzuki–Miyaura coupling reaction to provide the axially chiral biaryl products in good yields with good stereoselectivities (up to 68% ee).

Efficient Syntheses of Korupensamines A, B and Michellamine B by Asymmetric Suzuki-Miyaura Coupling Reactions

Efficient asymmetric Suzuki-Miyaura coupling reactions are employed for the first time in total syntheses of chiral biaryl natural products korupensamine A and B in combination with an effective diastereoselective hydrogenation, allowing ultimately a concise and stereoselective synthesis of michellamine B. Chiral monophosphorus ligands L1-3 are effective for the syntheses of a series of functionalized chiral biaryls by asymmetric Suzuki-Miyaura coupling reactions in excellent yields and enantioselectivities (up to 99% ee). The presence of a polar-π interaction between the highly polarized BOP group and the extended π system of arylboronic acid coupling partner is believed to be important for the high enantioselectivity.

ChemInform Abstract: Highly Diastereoselective Synthesis of Atropisomeric Bridged P,N‐Ligands and Their Applications in Asymmetric Suzuki—Miyaura Coupling Reaction.

AbstractElectron‐withdrawing groups in the boronic acids lead to diminished the yields and enantioselectivities.

Highly Diastereoselective Synthesis of Atropisomeric Bridged P,N‐Ligands and Their Applications in Asymmetric Suzuki–Miyaura Coupling Reaction

AbstractThree novel atropisomeric bridged P,N‐ligands were prepared using a highly efficient central‐to‐axial transfer strategy as the protocol. The new chiral ligands were successfully applied in the palladium‐catalyzed asymmetric Suzuki–Miyaura coupling reaction, Up to 98% yield and 82% ee were obtained in the enantioselective synthesis of axially chiral biarylphosphonates.

ChemInform Abstract: Highly Efficient Synthesis of a Class of Novel Chiral‐Bridged Atropisomeric Monophosphine Ligands via Simple Desymmetrization and Their Applications in Asymmetric Suzuki—Miyaura Coupling Reaction.

AbstractAmong various derivatives, ligand (I) is found to be the most efficient one to produce axially chiral organophosphorus compounds.

Efficient Chiral Monophosphorus Ligands for Asymmetric Suzuki–Miyaura Coupling Reactions

A series of novel P-chiral monophosphorus ligands exhibit efficiency in asymmetric Suzuki-Miyaura coupling reactions, enabling the construction of an array of chiral biaryl products in high yields and excellent enantioselectivities (up to 96% ee) under mild conditions. The carbonyl-benzooxazolidinone moiety in these chiral biaryl products allows facile derivatization for further synthetic applications. A computational study has revealed that a π-π interaction between the two coupling partners can enhance the enantioselectivity of the coupling reaction.

Highly Efficient Synthesis of a Class of Novel Chiral-Bridged Atropisomeric Monophosphine Ligands via Simple Desymmetrization and Their Applications in Asymmetric Suzuki–Miyaura Coupling Reaction

A series of novel chiral-bridged atropisomeric monophosphine ligands were synthesized via convenient and simple pathways. The prepared ligands, especially for ligand 7d, were found to be highly effective in the Pd-catalyzed Suzuki-Miyaura coupling reaction. The steric hindrance and electronic effect of substrates on the reactivity and enantioselectivity were explored preliminarily.