Conjugate Addition Of Arylboronic Acids Research Articles

Cu-Catalyzed Asymmetric Arylation of Enone Diesters with Arylboronic Acids.

The Cu-catalyzed asymmetric conjugate addition of arylboronic acids to enone diesters is reported. This operationally simple and scalable reaction proceeded under mild conditions. The practical utility of this approach was demonstrated by the synthesis of structurally important γ-lactones and a cyclopentene that bear an aryl group. Mechanistic studies revealed that two different copper catalytic species work synergistically in the reaction.

Synthesis and neuroprotective activity of 3-aryl-3-azetidinyl acetic acid methyl ester derivatives.

A library of 3-aryl-3-azetidinyl acetic acid methyl ester derivatives was prepared from N-Boc-3-azetidinone employing the Horner-Wadsworth-Emmons reaction, rhodium(I)-catalyzed conjugate addition of arylboronic acids, and subsequent elaborations to obtain N-unprotected hydrochlorides, N-alkylated and N-acylated azetidine derivatives. The compounds were evaluated for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity, revealing several derivatives to possess AChE inhibition comparable to that of the AChE inhibitor rivastigmine. The binding mode of the AChE inhibitor donepezil and selected active compounds 26 and 27 within the active site of AChE was studied using molecular docking. Furthermore, the neuroprotective activity of the prepared compounds was evaluated in models associated with Parkinson's disease (salsolinol-induced) and aspects of Alzheimer's disease (glutamate-induced oxidative damage). Compound 28 showed the highest neuroprotective effect in both salsolinol- and glutamate-induced neurodegeneration models, and its protective effect in the glutamate model was revealed to be driven by a reduction in oxidative stress and caspase-3/7 activity.

Palladium-Catalyzed Asymmetric Conjugate Addition of Arylboronic Acids to α,β-Unsaturated Lactams: Enantioselective Construction of All-Carbon Quaternary Stereocenters in Saturated Nitrogen-Containing Heterocycles.

Stereogenic nitrogen-containing heterocycles are ubiquitous in natural products and pharmaceutical compounds, but methods for their enantioselective construction have remained elusive. We report a general method for the asymmetric conjugate addition of arylboronic acids to β-alkyl/aryl α,β-unsaturated lactams that affords chiral β,β-disubstituted lactams. The transformation is operationally simple and air- and moisture-tolerant and uses a commercially available (S)-t-Bu-PyOx ligand. The method is high-yielding (up to 95% yield) and enantioselective (up to 97% ee) for a wide range of arylboronic acids and α,β-unsaturated lactams, including those with different ring sizes.

Covalent organic framework supported Pd(II)‐catalyzed conjugate additions of arylboronic acids to α,β‐unsaturated carboxylic acids

A palladium(II)‐coordinated covalent organic framework (Pd(II)@COF) was mechanochemically synthesized from [2,2′‐bipyridine]‐5,5′‐diamine (Bpy) and 1,3,5‐triformylphloroglucinol (Tp), which was demonstrated as a catalyst for conjugate addition of arylboronic acids to unreactive α,β‐unsaturated carboxylic acids in aqueous media (water/acetone = 1:1). Modest to good yields were obtained for most substrates, and studies on the catalyst recyclability showed that the heterogeneous catalyst gave >80% yields in the first 4 cycles. This research broadens the application of COFs supported catalysis and gave a new option for Pd(II)‐catalysis.

Discussion Addendum for: Preparation of (S)-tert-ButylPyOx and Palladium-Catalyzed Asymmetric Conjugate Addition of Arylboronic Acids.

Discussion Addendum for: Preparation of (S)-tert-ButylPyOx and Palladium-Catalyzed Asymmetric Conjugate Addition of Arylboronic Acids.

9-(Diphenylphosphino)anthracene-based phosphapalladacycle catalyzed conjugate addition of arylboronic acids to electron-deficient alkenes

9-(Diphenylphosphino)anthracene-based phosphapalladacycle catalyzed conjugate addition of arylboronic acids to electron-deficient alkenes such asα,β-unsaturated ketones, esters, nitrile and nitroalkenes gave corresponding β-arylated alkanes in good yields and achieved TON up to 700.

Tricyclic Sulfoxide–Alkene Hybrid Ligands for Chiral Rh(I) Complexes: The “Matched” Diastereomer Catalyzes Asymmetric C–C Bond Formations

Deprotonation of phenyldibenzo[b,f]tropylidene (8) with LDA/t-BuOK followed by quenching with either diastereomer of inexpensive glucose-based t-Bu-sulfinate (R)- or (S)-11 affords a sulfoxide–alkene hybrid ligand as the diastereomeric pairs (SS,SC)-9/(SS,RC)-10 and (RS,RC)-9/(RS,SC)-10, respectively, which via chromatographic/recrystallization may be separated into the four isomers. The optically pure diastereomeric ligands (SS,SC)-9 and (SS,RC)-10 react with [RhCl(coe)2]2 to form the dinuclear complexes (RS,SC)-11 and (RS,RC)-12, respectively, in which the bidentate ligands coordinate the metal centers through the sulfur and alkene donor functions. These complexes catalyze the conjugate addition of arylboronic acids to cyclic Michael acceptors with enantioselectivities of up to 99% ee. DFT calculations show the preponderant influence of planar chirality of the ligand alkene function. The enantioselectivity switch observed between (RS,SC)-11 and (RS,RC)-12 is explained by the inverted cis–trans coordinations of the substrate molecules in catalytic steps.

Stereoconvergent Conjugate Addition of Arylboronic Acids to α-Angelica Lactone Derivatives: Synthesis of Stereochemically Complex γ-Butyrolactones.

Catalyzed stereoconvergent 1,4-additions to unsaturated carbonyls are rare but of high potential value. This letter details the development of enantioselective arylation reactions of boronic acids and β,γ-butenolides. These reactions are catalyzed by commercially available hydroxy[(S)-BINAP]-rhodium(I) dimer to afford stereochemically complex γ-butyrolactone derivatives. The reaction products provide functionality amenable to further manipulation and can lead to products with up to three contiguous stereocenters. The reaction proceeds under a dynamic kinetic resolution manifold by isomerizing the achiral starting material into an interconverting mixture of enantiomeric conjugate acceptors, followed by catalyst-controlled, enantiomer-selective 1,4-addition. Base-promoted racemization of the intermediate α,β-butenolide is possible due to the high kinetic and thermodynamic acidity of the γ-proton.

Asymmetric Synthesis of Functionalized Phenylalanine Derivatives via Rh-Catalyzed Conjugate Addition and Enantioselective Protonation Cascade.

The asymmetric conjugate addition of arylboronic acids to N-phthalimidodehydroalanine 1i catalyzed by Rh(I)/L1a enables the facile preparation of chiral functionalized phenylalanines. The reaction proceeds by a conjugate addition and enantioselective protonation cascade, affording a rhodium enolate that undergoes re-face protonation. The reaction tolerates various arylboronic acids and can be used in the gram-scale synthesis of (S)-phenylalanine hydrochloride, demonstrating the reaction scope and the synthetic feasibility of the process.

A Pd(II)‐Functionalized Covalent Organic Framework for Catalytic Conjugate Additions of Arylboronic Acids to β,β‐Disubstituted Enones

AbstractA palladium(II)‐functionalized covalent organic framework (Pd@TpBpy COF) constructed from 1,3,5‐triformylphloroglucinol (Tp) and [2,2′‐bipyridine]‐5,5′‐diamine (Bpy) is reported as a recyclable catalyst for conjugate additions in aqueous media. Additions of an array of stereoelectronically diverse arylboronic acid nucleophiles to β,β‐disubstituted enones form a variety of ketones containing benzylic all‐carbon quaternary centers in up to 92 % isolated yield. Studies on the recyclability of Pd@TpBpy COF show this catalyst remains active through at least 7 cycles and shows superior stability to related MOF catalysts with bipyridine linker units.

Rh‐Catalyzed Asymmetric Conjugate Addition of Arylboronic Acids to 3‐Arylpropenoates: Enantioselective Synthesis of (R)‐Tolterodine

A highly enantioselective conjugate addition of arylboronic acids to 3‐arylpropenoates is presented. The rhodium complexes obtained from deoxycholic acid derived binaphthyl phosphites showed good activity as well as very high enantioselectivity (ee up to 99 %) in the conjugate addition to different ethyl‐3‐arylpropenoates, allowing to obtain useful chiral building blocks for the synthesis of active pharmaceutical ingredients. The method was applied to the enantioselective synthesis of the antimuscarinic drug (R)‐tolterodine.

Developing Chiral Dibenzazepine-Based S(O)-Alkene Hybrid Ligands for Rh(I) Complexation: Catalysts for the Base-Free Hayashi–Miyaura Reaction

A stereodivergent synthesis using inexpensive reagents, i.e., dibenzazepine and glucose-derived t-Bu-sulfinate diastereomers (RS)-6 or (SS)-6, affords respective S(O)-alkene hybrid ligands (S)-7 and (R)-7 on gram scales and in excellent optical purity (ee > 99%). Phenyl substitution of the dibenzoazepine backbone generates planar chirality to give epimerization-resistant (pS,RS)-10 diastereoisomer in high isomeric purity. Furthermore, the crystal structure of widely used sulfinate (RS)-6 is disclosed for the first time since its discovery a quarter of a century ago. Ligands 7 and 10 coordinate Rh(I) in a bidentate fashion through the S atoms and the alkene functions as evidenced by the crystal structures of complexes (R)-11 and (SN,SS)-12. (R)-11 catalyzes the conjugate addition of arylboronic acids to enones with enantioselectivities of up to 77% ee. The reaction proceeds smoothly also under base-free conditions at 40 °C. The planar chirality in ligand (pS,RS)-10 is shown to override and invert the sense of chiral induction predicted by the configuration of the sulfur donor atom.

Diastereoselective synthesis of β-amino ketone and acid derivatives by palladium-catalyzed conjugate addition

The first diastereoselective synthesis of β-amino ketone and β-amino acid derivatives by palladium-catalyzed conjugate addition of arylboronic acids to chiral β-enamino ketones and β-enamino esters is reported. The catalytic system employing (S)-4-(tert-butyl)oxazolidin-2-one as the chiral auxiliary in water under an air atmosphere provides β-amino ketone and β-amino acid derivatives in high yields with excellent diastereoselectivity.

Chiral Sulfinyl-Based Olefin Ligands for Rhodium-Catalysed Asymmetric Conjugate Addition of Arylboronic Acids to Cyanoalkenes

A rhodium/sulfinyl-based olefin ligand-catalysed asymmetric conjugate addition of arylboronic acids to cyanoalkenes without activation groups has been developed, where p-tolylsulfinyl-functionalised olefin ligands have been shown to be effective and with moderate enantioselectivities. This is the first example of applying chiral sulfinyl-based olefin ligands in the catalytic asymmetric addition to cyanoalkenes.

Cationic Pd(II)/bipyridine-catalyzed conjugate addition of arylboronic acids to α,β-unsaturated carboxylic acids in aqueous media

An in-situ generated cationic Pd(II)/bipyridine-catalyzed conjugate addition of arylboronic acids to α,β-unsaturated carboxylic acids in water was developed and optimized. For most substrates, nearly quantitative yields were given, and the products can be purified by simple washing without column chromatography. The reaction can be scaled up to 1.0 g easily with excellent yields. Also the loading of catalyst can be lowered to 1.0 mol% with modest yields, and the reaction provided a mild and easy way to synthesize β-disubstituted carboxylic acids.

Palladium-Catalyzed Diastereoselective Synthesis of 3-Arylbutanoic Acid Derivatives.

The first palladium-catalyzed diastereoselective conjugate addition of arylboronic acids to chiral imides is reported. The catalytic system employing 4-tert-butyloxazolidin-2-one as the chiral auxiliary in a mixed solvent system of MeOH/H2O (1:3) under an air atmosphere provides the optically active 3-arylbutanoic acid derivatives in excellent yields with high diastereoselectivity.

Palladium-Catalyzed Conjugate Addition of Arylboronic Acids

Key words palladium catalysis - asymmetric conjugate addition - quaternary centers

Diastereoselective Palladium-Catalyzed Conjugate Addition of Arylboronic Acids to α-Substituted Cyclic Enones

A palladium-catalyzed conjugate addition of arylboronic acids to α-substituted cyclic enones was developed to give α,β-disubstituted ketones with high diastereoselectivity. Mechanistic investigation showed that the high diastereoselectivity was realized through epimerization.

Enantioselective, Palladium-Catalyzed Conjugate Additions of Arylboronic Acids to Form Bis-benzylic Quaternary Stereocenters.

We report enantioselective, palladium-catalyzed conjugate additions of arylboronic acids to β-aryl, β,β-disubstituted enones to generate ketones containing bis-benzylic quaternary stereocenters. A catalyst generated from palladium trifluoroacetate and (S)-4-tert-butyl-2-(2-pyridyl)oxazoline ligand ((S)-t-BuPyOx) promotes conjugate additions of a wide range of arylboronic acids to a variety of β-aryl, β,β-disubstituted enones. Iterative addition of the arylboronic acid to minimize undesired protodeboronation pathways leads to efficient formation of the corresponding ketones containing bis-benzylic quaternary stereocenters in up to 92% yield and up to 93% enantioselectivity.

Pd(II)/Bipyridine-Catalyzed Conjugate Addition of Arylboronic Acids to α,β-Unsaturated Carboxylic Acids. Synthesis of β-Quaternary Carbons Substituted Carboxylic Acids.

Pd(II)/bipyridine-catalyzed conjugate addition of arylboronic acids to α,β-unsaturated carboxylic acids (including β,β-disubstituted acrylic acids) was developed and optimized, which provided a mild and convenient method for the highly challenging synthesis of β-quaternary carbons substituted carboxylic acids.