Lipase‐Catalyzed Dynamic Kinetic Resolution of C1‐ and C2‐Symmetric Racemic Axially Chiral 2,2′‐Dihydroxy‐1,1′‐biaryls

We have discovered that the racemization of configurationally stable, axially chiral 2,2′‐dihydroxy‐1,1′‐biaryls proceeds with a catalytic amount of a cyclopentadienylruthenium(II) complex at 35–50 °C. Combining this racemization procedure with lipase‐catalyzed kinetic resolution led to the first lipase/metal‐integrated dynamic kinetic resolution of racemic axially chiral biaryl compounds. The method was applied to the synthesis of various enantio‐enriched C₁‐ and C₂‐symmetric biaryl diols in yields of up to 98 % and enantiomeric excesses of up to 98 %, which paves the way for new developments in the field of asymmetric synthesis.     

Efficient Synthesis of Diaryl Ketones by Nickel‐Catalyzed Negishi Cross‐Coupling of Amides by Carbon–Nitrogen Bond Cleavage at Room Temperature Accelerated by a Solvent Effect

The first Negishi cross‐coupling of amides for the synthesis of versatile diaryl ketones by selective C?N bond activation under exceedingly mild conditions is reported. The cross‐coupling was accomplished with bench‐stable, inexpensive precatalyst [Ni(PPh₃)₂Cl₂] that shows high functional‐group tolerance and enables the synthesis of highly functionalized diaryl ketone motifs. The coupling occurred with excellent chemoselectivity favoring the ketone (cf. biaryl) products. Notably, this process represents the mildest conditions for amide N?C bond activation accomplished to date (room temperature, <10 min). Considering the versatile role of polyfunctional biaryl ketone linchpins in modern organic synthesis, availability, and excellent functional‐group tolerance of organozinc reagents, this strategy provides a new platform for amide N?C bond/organozinc cross‐coupling under mild conditions.     

Nanostructured Pyrophosphate Na2PdP2O7‐Catalyzed Suzuki‐Miyaura Cross‐Coupling Under Microwave Irradiation

Nanostructured palladium pyrophosphate (Na₂PdP₂O₇) catalyst was synthesized and well characterized by using different techniques (TGA, XRD, SEM, TEM....). This nanocatalyst exhibited excellent catalytic activity in the synthesis of biaryl compounds via Suzuki‐Miyaura cross‐coupling to produce their corresponding products in good to excellent yields under mild conditions. The catalyst is recyclable and was recycled for four runs for the reaction of 4‐bromoacetophenone with phenylboronic acid without appreciable loss of its catalytic activity.     

Tetralones as precursors for the synthesis of 2,2′-disubstituted 1,1′-binaphthyls and related compounds

Using tetralones as starting materials, the synthesis of biaryl compounds is described in this paper. The tetralones were initially converted into 1-bromo-3,4-dihydro-2-naphthalenecarbaldehydes before effecting aromatization into the corresponding naphthalenes. These products were then subjected to Suzuki-Miyaura cross-coupling reactions, with a variety of aromatic boronic acids containing substituents in the ortho position, to afford biaryl compounds. The biaryl compounds possess heteroatom containing substituents ortho to the newly formed biaryl axis.     

Synthesis of Axially Chiral Biaryl‐2‐amines by PdII‐Catalyzed Free‐Amine‐Directed Atroposelective C−H Olefination

A simple and ubiquitously present group, free amine, is used as a directing group to synthesize axially chiral biaryl compounds by Pd^II‐catalyzed atroposelective C?H olefination. A broad range of axially chiral biaryl‐2‐amines can be obtained in good yields with high enantioselectivities (up to 97 % ee). Chiral spiro phosphoric acid (SPA) proved to be an efficient ligand and the loading could be reduced to 1 mol % without erosion of enantiocontrol in gram‐scale synthesis. The resulting axially chiral biaryl‐2‐amines also provide a platform for the synthesis of a set of chiral ligands.     

Hiyama cross‐coupling reaction using Pd(II) nanocatalyst immobilized on the surface of Fe3O4@SiO2

We report a simple process for the synthesis of Fe₃O₄@SiO₂/APTMS (APTMS = 3‐aminopropyltrimethoxysilane) core–shell nanocatalyst support. The new nanocatalyst was prepared by stabilization of Pd(cdha)₂ (cdha = bis(2‐chloro‐3,4‐dihydroxyacetophenone)) on the surface of the Fe₃O₄@SiO₂/APTMS support. The structure and composition of this catalyst were characterized using various techniques. An efficient method was developed for the synthesis of a wide variety of biaryl compounds via fluoride‐free Hiyama cross‐coupling reactions of aryl halides with arylsiloxane, with Fe₃O₄@SiO₂/APTMS/Pd(cdha)₂ as the catalyst under reaction conditions. This methodology can be performed at 100°C through a simple one‐pot operation using in situ generated palladium nanoparticles. High catalytic activity, quick separation of catalyst from products using an external magnetic field and use of water as green solvent are attributes of this protocol.     

Expedient synthesis of 4-O-methylhonokiol via Suzuki-Miyaura cross-coupling

Concise and practical synthesis of 4-O-methylhonokiol was achieved in 34% overall yield. The key features of our synthesis include chemoselective ortho-mono bromination of phenol as well as biaryl formation via Suzuki-Miyaura cross-coupling, in which bromophenol was reacted with potassium aryltrifluoroborate using Pd(OAc)₂ and RuPhos under microwave conditions.     

Factorial design evaluation of the Suzuki cross-coupling reaction using a magnetically recoverable palladium catalyst

A magnetically recoverable catalyst [Fe₃O₄@SiO₂-AEAPTMS-Pd(II)] was prepared, fully characterized and had its catalytic activity evaluated on the Suzuki cross-coupling reaction under microwave irradiation. The reaction conditions for the synthesis of biaryl compounds was optimized in two stages - an initial fractional design 2⁴, in which the parameters reaction time, temperature, solvent and catalyst loading were evaluated, followed by a Doehlert design. The factorial design proved to be a viable approach for obtaining the optimal reaction conditions based on a relatively small number of experiments. Additionally, the biaryl derivatives synthesized by this method were obtained with good to excellent yields (71–96%) and the recovery and reuse of the palladium catalyst was also evaluated.     

A synthesis of (aR,7S)-(−)-N-acetylcolchinol and its conjugate with a cyclic RGD peptide

An asymmetric synthesis of (−)-N-acetylcolchinol is described based on a Suzuki-Miyaura coupling to generate the biaryl pharmacophore. The sole asymmetric centre was introduced by an asymmetric reduction of a dibenzosuberone derivative 24 using lithium borohydride in the presence of stoichiometric amounts of a chiral Lewis acid (TarB-NO₂). A conjugate between an α_Vβ₃ integrin-binding cyclic peptide c[RGDfK] and colchinol (adipoyl linker) was synthesised with an aim to deliver colchinol to solid tumours selectively.     

Palladium-catalysed symmetrical and unsymmetrical coupling of aryl halides

Pd(OAc)₂ is a convenient catalyst under basic conditions for the synthesis of symmetrical biaryl moieties from aryl halides. This homocoupling of aryl halides is a good catalytic alternative to classical biaryl formations involving stoichiometric amounts of metal. This method is compatible with sensitive functional groups. We also studied the extension of this reaction to unsymmetrical aryl coupling.     

Reagent‐Free C−H/N−H Cross‐Coupling: Regioselective Synthesis of N‐Heteroaromatics from Biaryl Aldehydes and NH3

An unprecedented synthesis of N‐heteroaromatics from biaryl aldehydes and NH₃ through reagent‐free C−H/N−H cross‐coupling has been developed. The electrosynthesis uses NH₃ as an inexpensive and atom‐economic nitrogen donor, requires no oxidizing agents, and allows efficient and regioselective access to a wide range of phenanthridines and structurally related polycyclic N‐heteroaromatic products.     

Dihedral‐Angle‐Controlled Crossover from Static Hole Delocalization to Dynamic Hopping in Biaryl Cation Radicals

In cases of coherent charge‐transfer mechanism in biaryl compounds the rates follow a squared cosine trend with varying dihedral angle. Herein we demonstrate using a series of biaryl cation radicals with varying dihedral angles that the hole stabilization shows two different regimes where the mechanism of the hole stabilization switches over from (static) delocalization over both aryl rings to (dynamic) hopping. The experimental data and DFT calculations of biaryls with different dihedral angles unequivocally support that a crossover from delocalization to hopping occurs at a unique dihedral angle where the electronic coupling (H _ab) is one half of reorganization (λ ), that is, H _ab=λ /2. The implication of this finding in non‐coherent charge‐transfer rates is being investigated.     

In Situ Generation of Ruthenium Carbonyl Phosphine Complexes as a Versatile Method for the Development of Enantioselective C−O Bond Arylation

We report here a method for in situ generation of various ruthenium carbonyl phosphine catalysts for arylation via cleavage of inert aromatic carbon–oxygen bonds. The use of catalyst systems consisting of [RuCl₂(CO)(p-cymene)], CsF, styrene, and phosphines enabled facile screening of phosphine ligands. Asymmetric C–O arylation was also achieved for atropo-enantioselective biaryl synthesis using a chiral monodentate phosphine ligand.     

Enantioselective total synthesis of parnafungin A1 and 10a-epi-hirtusneanine

The first and enantioselective total synthesis of the heterodimeric biaryl antifungal natural product parnafungin A1 as well as complex biaryl tetrahydroxanthone 10a-epi-hirtusneanine is accomplished, by employing cross-coupling through the benzoxaborole strategy to construct their sterically hindered biaryl cores. Besides the powerful Suzuki–Miyaura cross-coupling, the synthesis of parnafungin A1 also features a highly diastereoselective oxa-Michael addition to construct a tetrahydroxanthone skeleton, and an effective Zn-mediated reductive cyclization-Mitsunobu sequence to furnish the isoxazolidinone structure. Key innovations in total synthesis of 10a-epi-hirtusneanine include the employment of DTBS protection for functional group manipulation on the tetrahydroxanthone skeleton, stereoselective methylations, and complete reversal of the stereochemistry of the C5-hydroxy group using oxidation/Evans–Saksena reduction, as well as the strategy of preparing both complex tetrahydroxanthone monomers from the same chiral intermediate 25.

The first, enantioselective total synthesis of the heterodimeric biaryl antifungal natural product parnafungin A1 as well as 10a-epi-hirtusneanine is accomplished, using a cross-coupling strategy to construct their sterically hindered biaryl cores.     

A concise synthesis of a new xylyl-biaryl diphosphine ligand for asymmetric hydrogenation of ketones

A concise synthesis of a symmetrical biaryl diphosphine ligand bearing 3,5-dimethylphenyl substituents at phosphorus is described. The ruthenium catalysts [diphosphine RuCl₂ diamine] containing the new ligand Xyl-TetraPHEMP were found to be as active and as selective as the state-of-the-art catalysts for homogeneous asymmetric ketone hydrogenation.     

Jozimine A2: The First Dimeric Dioncophyllaceae‐Type Naphthylisoquinoline Alkaloid,with Three Chiral Axes and High Antiplasmodial Activity

A new dimeric naphthylisoquinoline alkaloid, jozimine A₂ ( 2 ), was isolated from the root bark of an Ancistrocladus species from the Democratic Republic of Congo. Its absolute stereostructure was determined by chemical, spectroscopic, and chiroptical methods, and confirmed by X‐ray crystallography. Jozimine A₂ ( 2 ) is one of the as yet very rare naphthylisoquinoline dimers whose central biaryl axis is rotationally hindered. Moreover, it is the first natural dimer of a Dioncophyllaceae‐type alkaloid, that is, lacking oxygen functions at C6, and bearing R configurations at C3 in its two isoquinoline portions. Despite this decreased steric hindrance, the outer biaryl axes are chiral, too, so that jozimine A₂ ( 2 ) has three consecutive stereogenic axes and, together with the four stereogenic centers, seven elements of chirality and is C₂‐symmetric. The new dimer exhibits excellent, and specific, antiplasmodial activity. To further confirm its stereostructure and for likewise testing the bioactivities of its (unnatural) atropo‐diastereomer, compound 2 was prepared by semi‐synthesis from the co‐occurring (and likewise synthetically available) dioncophylline A ( 5 ), along with its atropo‐diastereomer, 3′‐epi‐ 2 .     

Electron-Rich Aromatics Under Ball Milling: Oxidative Aryl-iodination Using I2-Oxone and Biarylation with I2

We report here a simple, efficient, and environmentally friendly methodology for electrophilic aryl-iodination of electron-rich arenes using I₂-oxone under ball milling. The reactions work efficiently under solvent-free conditions at room temperature. We have also shown that iodine could be used as catalyst for metal-free biaryl coupling of a few electron-rich substrates. In addition, one-pot multistep synthesis has been demonstrated for one substrate.     

Bisoxazoline ligands with an axial-unfixed biaryl backbone: the effects of the biaryl backbone and the substituent at oxazoline ring on Cu-catalyzed asymmetric cyclopropanation

The synthesis of novel C₂-symmetric bisoxazoline ligands with an axial-unfixed biaryl backbone and different substituents at the oxazoline ring is reported. The diastereomer equilibrium of these ligands in solution and their complexation behavior with the copper(I) ion were studied. Their application in Cu-catalyzed cyclopropanation of styrene, with diazoacetate, was carried out and the effects of the biaryl backbone and the substituent on the oxazoline ring in the catalysis were examined. The best result was obtained with the ligand having a 1,1′-binaphthyl backbone and a t-butyl group on the oxazoline ring, which afforded 89% de and 96% de for the trans- and cis-products of the above asymmetric cyclopropanation reaction, respectively.     

Optimized Palladium(0)‐catalyzed Suzuki Cross‐coupling Reaction of Polystyrene‐supported Selenenyl Flavanones: A Convenient Preparation of Biaryl‐chromen‐4‐one

Application of the Suzuki cross‐coupling reaction for efficient synthesis of diverse substituted biaryl‐chromen‐4‐ones using an optimized palladium(0) catalyst system is reported. The coupling of arylboronic acids with the resin‐bound bromoflavanones which were prepared by organoselenium‐induced regioselective intramolecular cyclization of bromo‐2‐hydroxylchalcones proceeded smoothly. Biaryl‐chromen‐4‐ones were synthesized by subsequent selenoxide syn‐elimination in good total yields.     

Photoinduced Miyaura Borylation by a Rare‐Earth‐Metal Photoreductant: The Hexachlorocerate(III) Anion

The first photoinduced carbon(sp²)–heteroatom bond forming reaction by a rare‐earth‐metal photoreductant, a Miyaura borylation, has been achieved. This simple, scalable, and novel borylation method that makes use of the hexachlorocerate(III) anion ([Ce^IIICl₆]^3?, derived from CeCl₃) has a broad substrate scope and functional‐group tolerance and can be conducted at room temperature. Combined with Suzuki–Miyaura cross‐coupling, the method is applicable to the synthesis of various biaryl products, including through the use of aryl chloride substrates.