Miyaura Borylation Research Articles

ChemInform Abstract: Convenient Synthesis of Arylboronates Through a Synergistic Pd/Cu‐Catalyzed Miyaura Borylation Reaction under Atmospheric Conditions.

A highly efficient and practical borylation reaction of aryl iodides with bis(pinacolato)diboron has been established. By using Pd(OAc)2, CuI, and PPh3 as a ligand at room temperature under air in the presence of Cs2CO3, the protocol proved to be general. Various functionalized arylboronates were obtained in moderate to excellent yields. In addition, a possible reaction mechanism was proposed.

ChemInform Abstract: “Nok”: A Phytosterol‐Based Amphiphile Enabling Transition‐Metal‐Catalyzed Couplings in Water at Room Temperature.

AbstractThe synthesis of the title third‐generation amphiphile/surfactant (NOK) is described (soon be commercially available from Aldrich), along with the successful application as an efficient surfactant in several aqueous cross coupling reactions (metathesis, Suzuki‐Miyaura, Sonogashira, Heck, Stille, Miyaura borylation, amination).

Clean and fast cross-coupling of aryl halides in one-pot.

Unsymmetrically coupled biaryls are synthesized in high yield starting from different aryl bromides and bis(pinacolato)diboron by carrying out the Miyaura borylation reaction followed by the Suzuki–Miyaura reaction in the same reaction pot over 1–2 mol % SiliaCat DPP-Pd. The SiliaCat DPP-Pd catalyst is air-stable and the method does not require the use of inert conditions. The use of non-toxic isopropanol or 2-butanol as reaction solvent further adds to the environmental benefits of this new green synthetic methodology.

Convenient Synthesis of Arylboronates through a Synergistic Pd/Cu‐Catalyzed Miyaura Borylation Reaction under Atmospheric Conditions

AbstractA highly efficient and practical borylation reaction of aryl iodides with bis(pinacolato)diboron has been established. By using Pd(OAc)2, CuI, and PPh3 as a ligand at room temperature under air in the presence of Cs2CO3, the protocol proved to be general. Various functionalized arylboronates were obtained in moderate to excellent yields. In addition, a possible reaction mechanism was proposed.

The Impact of Palladium(II) Reduction Pathways on the Structure and Activity of Palladium(0) Catalysts

Two roads diverged: The mechanism of in situ PdII catalyst activation to generate an active {LnPd0} catalyst from an air-stable PdII precursor was examined using the standard conditions of a Miyaura borylation reaction. Two pathways for catalyst activation exist under these conditions, producing two structurally and chemically distinct {LnPd0} complexes (see scheme). As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Iron‐Catalysed Borylation of Arenediazonium Salts to Give Access to Arylboron Derivatives via Aryl(amino)boranes at Room Temperature

AbstractComplementary to previously described Miyaura borylation methods, a new access to boron derivatives via aryl(amino)boranes is described. Direct coupling between aryldiazonium salts and diisopropylaminoborane is catalysed by 0.1% ferrocene leading to the formation of a carbon‐boron bond. The obtained aryl(amino)boranes could eventually then be transformed into boronic acids, boronates or borates.

Solid‐Phase Synthesis of Biaryl Cyclic Peptides Containing a 3‐Aryltyrosine

AbstractA concise and efficient solid‐phase synthesis of biaryl cyclic peptides containing a Phe–Tyr or a Tyr–Tyr linkage has been accomplished. The key steps include a Miyaura borylation of a resin‐bound 3‐iodotyrosine and a microwave‐assisted Suzuki–Miyaura reaction for the formation of the macrocycle. First, the feasibility of the solid‐phase Miyaura borylation of a 3‐iodotyrosyltripeptide was established. Then, the Suzuki–Miyaura reaction was applied to the cross‐coupling of linear 3‐boronotyrosine‐containing peptidyl resins with iodobenzene and with halogenated aromatic amino acids. Finally, this methodology was extended to the synthesis of biaryl cyclic peptides through the preparation of a linear peptidyl resin containing both the required boronate and halogenated derivatives, followed by a microwave‐assisted Suzuki–Miyaura macrocyclization.

Design and synthesis of boron containing 2,4-disubstituted-phthalazin-1(2H)-one and 3,7-disubstituted-2H-benzo[b][1,4] oxazine derivatives as potential HGF-mimetic agents

We synthesized boron containing 2-(4-methoxybenzyl)-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioaborolan-2-yl)phenyl) phthalazin-1(2H)-one 3 and 7-methyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-2H-benzo[b][1,4] oxazine 8. The reaction of compound 2 with B2pin2 using potassium acetate as the base and Pd(PPh3)2Cl2 as the catalyst, produced the corresponding boron-containing derivative 3 as a white solid in 65% yield. Alternatively, we have synthesized compound 8 as a yellow solid in 59% yield using the Miyaura borylation reaction. The potassium trifluoro(4-(-methyl-2H-benzo[b][1,4]oxazine-3-yl)phenylborate 9 was then obtained after treatment of 8 with aqueous solution of KF2H in methanol as white solid product in 60% yield. The biological activities of the synthetic compounds are currently being evaluated.

Efficient Monophosphorus Ligands for Palladium-Catalyzed Miyaura Borylation

In combination with the Bedford Pd precursor, the new biaryl monophosphorus ligand 5 was efficient for palladium-catalyzed Miyaura borylation of sterically hindered aryl bromides at low catalyst loadings.

Solid-phase synthesis of biaryl cyclic peptides by borylation and microwave-assisted intramolecular Suzuki–Miyaura reaction

Miyaura borylation and Suzuki–Miyaura cross-coupling have been combined to set up an efficient strategy for the solid-phase synthesis of biaryl cyclic peptides. The Miyaura borylation was the key step in obtaining the linear peptidyl resin precursor containing both the boronate and the halogenated derivative of an aromatic amino acid. The Suzuki–Miyaura macrocyclization was performed under microwave irradiation leading to biaryl cyclic peptides of different ring sizes.

Synthesis and properties of starburst amorphous molecules: 1,3,5-Tris(1,8-naphthalimide-4-yl)benzenes

A series of starburst amorphous molecules derived from 1,3,5-tris(1-naphthyl)benzene are synthesized by a palladium-catalyzed Miyaura borylation and palladium-catalyzed Suzuki coupling reactions. These starburst compounds have the abilities to form uniform amorphous thin films and possess glass transition temperatures as high up to 254 °C. The high current density and luminance of organic light emitting diodes fabricated indicate that these compounds own good electron-transporting properties. These compounds hence have the potential to be used as electron-transporting materials in organic semiconducting devices.

Biaryl Peptides from 4‐Iodophenylalanine by Solid‐Phase Borylation and Suzuki–Miyaura Cross‐Coupling (Eur. J. Org. Chem. 8/2010)

AbstractThe cover picture shows the skyline of the old part of Girona in northeast Catalonia, Spain. In the foreground is one of the many bridges that span the river Onyar from the new part of the town to the Jewish quarter. This bridge, named the Pont de Sant Feliu, is the usual starting point for visiting this quarter. It offers a nice view of the narrow colourful houses that back onto the river and allows an impressive view of the Cathedral and the Sant Feliu church. Built in different styles (11th–17th century AD), the Cathedral preserves a Gothic nave with the widest arched span in the world. In this picture, the Pont de Sant Feliu serves as a means to depict the synthesis of a 4‐arylphenylalanine tripeptide from a resin‐bound phenylalanine boronate. Details can be found in the article by L. Feliu et al. on p. 1461 ff, and results on the formation of the boronate through a solid‐phase Miyaura borylation are also discussed.

Graphical Abstract: Eur. J. Org. Chem. 8/2010

AbstractThe cover picture shows the skyline of the old part of Girona in northeast Catalonia, Spain. In the foreground is one of the many bridges that span the river Onyar from the new part of the town to the Jewish quarter. This bridge, named the Pont de Sant Feliu, is the usual starting point for visiting this quarter. It offers a nice view of the narrow colourful houses that back onto the river and allows an impressive view of the Cathedral and the Sant Feliu church. Built in different styles (11th–17th century AD), the Cathedral preserves a Gothic nave with the widest arched span in the world. In this picture, the Pont de Sant Feliu serves as a means to depict the synthesis of a 4‐arylphenylalanine tripeptide from a resin‐bound phenylalanine boronate. Details can be found in the article by L. Feliu et al. on p. 1461 ff, and results on the formation of the boronate through a solid‐phase Miyaura borylation are also discussed.

Biaryl Peptides from 4‐Iodophenylalanine by Solid‐Phase Borylation and Suzuki–Miyaura Cross‐Coupling

AbstractResin‐bound phenylalanine boronates were prepared by solid‐phase Miyaura borylation of 4‐iodophenylalanine peptides. Subsequent arylation through a Suzuki–Miyaura cross‐coupling was carried out using a variety of aryl halides under conventional heating and under microwave irradiation. Microwaves greatly enhanced the arylation, shortening thereaction time and providing the biaryl peptides in higherpurities.

Synthesis of Biindolyls via Palladium-Catalyzed Reactions

An unprecedented synthesis of a range of high value homo- and heterobiindolyls is presented. The one-pot Miyaura borylation and subsequent Suzuki-Miyaura coupling sequence allows for the construction of the highly sterically congested C-C bond between two bromoindoles in modest to good overall yields.

Novel Functionalized Trisubstituted Allylboronates via Hosomi—Miyaura Borylation of Functionalized Allyl Acetates.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Novel functionalized trisubstituted allylboronates via Hosomi-Miyaura borylation of functionalized allyl acetates.

[reaction: see text] A series of novel functionalized achiral and chiral allylboronates have been synthesized via the nucleophilic addition of boronates on allyl acetates derived via vinylalumination or Baylis-Hillman reaction of aldehydes. These reagents, upon allylboration with aldehydes, furnish beta-substituted-alpha-methylene-gamma-butyrolactones stereoselectively.

Synthesis of a dicyclobutylideneethane derivative via sequential palladium-catalyzed Miyaura borylation and Suzuki coupling

An efficient synthesis of a dicyclobutylideneethane derivative was achieved using a palladium-catalyzed reaction of a substituted (bromomethylene)cyclobutane with bis(pinacolato)diboron. The reaction mechanism was investigated in detail. The Suzuki cross-coupling reaction of a (bromomethylene)cyclobutane with arylboronic acid was also achieved.

A convenient preparation of dityrosine via Miyaura borylation–Suzuki coupling of iodotyrosine derivatives

Dityrosine has been prepared from 3-iodo- l-tyrosine derivatives by sequential Miyaura borylation and Suzuki coupling reactions. A tandem borylation–coupling protocol results in improved yields of the dityrosine derivatives. Suitable protecting group strategies are employed to allow for global deprotection as the final step.

Selective formation of alpha-methylene-beta-amino acid derivatives through the aza version of the Baylis-Hillman reaction.

The current thesis presents the optimization and generalization of the Baylis-Hillman reaction applied to in situ generated imines, i.e. a three-component aza- Baylis-Hillman reaction. We found that the title reaction proceeds most efficiently in the presence of a combination of catalysts, i.e. 3-hydroxyquinuclidine (0.15 equiv) and titanium isopropoxide (0.02 equiv), together with molecular sieves (4 A; activated powder; 200 mg/mmol substrate) at ambient temperature. Our study of the scope and limitations of this reaction, revealed that arylaldehydes and sulfonamides are the only imine precursors which both generate the corresponding imines in situ and facilitate a further reaction with the Michael acceptor in a Baylis-Hillman fashion. Among the Michael acceptors tested, acrylates and acrylonitrile demonstrate high reactivity, while acrylamides and β-substituted acrylates do not participate in the reaction.The optimized conditions applied to the above range of substrates results in good-to-excellent yields of the desired amine-products (53-94%) and very high chemoselectivity (83- >99%). Furthermore, the reaction times observed under these conditions are considerably shorter than those previously reported for the aza-Baylis-Hillman reaction.In the development of a stereoselective version of the title reaction, the use of a chiral catalyst proved to be most effective. Thus, an enantiomeric excess up to 74% can be obtained with β-Isocupreidine. With chiral imine precursors or chiral acrylates, the diastereoselectivity attained was poor. No asymmetric induction was observed when chiral Lewis acids were employed as a co-catalyst.The α-methylene-β-amino acid derivatives obtained via the three-component aza-Baylis-Hillman reaction were subjected to further transformation. Carbon chain elongation at the olefinic end of the amine-adduct was attempted. For this purpose, the Miyaura borylation protocol could be successfully applied. The subsequent Suzuki-type cross-coupling reaction resulted predominantly in hydrolysis of the boronate intermediate, together with formation of the amine-adduct via β-hydride elimination. The optimal conditions for this latter reaction remain to be found.Finally, 2,5-dihydropyrroles have been synthesized from aza-Baylis-Hillman adducts, via a short and efficient route in which the key step is a microwave-assisted ring-closing metathesis of the N-allylated amine-adducts.