Orbital phase in Suzuki–Miyaura cross-coupling reactions

We investigated the electronic structures of the transition states of the oxidative addition, transmetalation, and reductive elimination steps in the catalytic cycle of the title reaction. The frontier orbital theory was surprisingly found to be applicable whereas any d orbitals of transition metals can be a main component of frontier orbitals because of their close energies. Visualizing the actually calculated HOMO and LUMO of the two parts of the transition structure of each step clearly demonstrated their orbital phase matching in favor of overlapping. The HOMO for the transmetalation step suggests that electron-donating ability of the carbon–metal bond of organometallic compounds (RMX) could control the reactivities of related cross-coupling reactions. The energies of the molecular orbitals having large amplitudes of the C–M bonding orbitals of RMX explain why the Suzuki–Miyaura cross-coupling reaction needs a base while the Kumada–Tamao and Negishi reactions take place without any bases.     

Preparation of C-arylglycals via Suzuki–Miyaura cross-coupling of dihydropyranylphosphates

The preparation of C-arylglycals has been accomplished by employing the Suzuki–Miyaura cross-coupling reaction of dihydropyranylphosphates with arylboronate esters. The reaction is tolerant of both electron-donating (EDG) and electron-withdrawing (EWG) groups on the aromatic ring and affords the corresponding C-arylglycals in good to excellent yields (68–97%). Additionally, the ketene acetal phosphate derived from 6-deoxy-3,4-di-O-benzyl-l-rhamnal also couples efficiently to yield C-arylglycals in excellent yields.     

Suzuki–Miyaura cross-coupling of aryldiazonium silica sulfates under mild and heterogeneous conditions

An efficient and straightforward procedure for the Suzuki–Miyaura cross-coupling reaction was studied by using aryldiazonium silica sulfates and sodium tetraphenylborate in the presence of a catalytic amount of Pd(OAc)₂. These reactions were carried out in water at room temperature without using additional ligands.     

Regioselective Suzuki–Miyaura cross-coupling reactions of the bis(triflate) of 4,7-dihydroxycoumarin

Arylated coumarins were prepared by site-selective Suzuki–Miyaura cross-coupling reaction of the bis(triflate) of 4,7-dihydroxycoumarin. The reactions proceeded by initial attack to the sterically more hindered position, due to electronic reasons.     

A highly efficient memantine-modified palladium catalyst for Suzuki–Miyaura cross-coupling reaction

A new simple Pd(memantine)₂Cl₂ complex was synthesized and characterized by ¹H NMR, ¹³C NMR and X-ray single crystal structure determination. The Suzuki–Miyaura reaction of aryl bromides catalyzed by Pd(memantine)₂Cl₂ complex was investigated in air with different temperature. The high turnover numbers of 650,000 have been obtained in the reaction of 4-bromonitrobenzene with phenylboronic acid at 80 °C. At room temperature, the complex also showed high activity for Suzuki–Miyaura cross-coupling reaction of aryl bromides with a wide range of functional groups under air, and the turnover number of up to 99,000 was achieved. The catalytic system also gives good yields toward the reaction of several heteroaryl bromides with thiophenylboronic acid.     

Carbohydrate-based phosphines as supporting ligand for palladium-catalyzed Suzuki–Miyaura cross-coupling reaction

Carbohydrate-based mono-phosphines (1 and 2) derived from glucose have been explored as supporting ligand for palladium-catalyzed Suzuki–Miyaura reaction. The combination of phosphine to palladium in a ratio of 2:1 resulted in a longer-living system than that in a ratio of 1:1. Using K₂CO₃ as base, aryl bromides as well as active aryl chlorides can be coupled nearly quantitatively by 0.1–0.2 mol % of 1/Pd(OAc)₂ with 95–99% of isolated yields. The amount of the catalyst could be lowered to 0.01 mol % under the optimized condition with 80% yield at room temperature. The carbohydrate hydroxyl group in 1 was found to contribute to catalytic activity.     

Suzuki–Miyaura cross-coupling reaction of aryl and heteroaryl pinacol boronates for the synthesis of 2-substituted pyrimidines

Suzuki–Miyaura cross-coupling reaction with 2-heteroarylboronic acids is generally challenging due to these acids easy decomposition. To overcome this problem, we developed a coupling method that uses 2-heteroaryl pinacol boronates in the presence of 1.0 mol % Pd(OAc)₂ and 2.0 mol % S-Phos with 4 equiv amount of LiOH in dioxane and H₂O at 80 °C for 30 min. This developed method allowed for the synthesis of a wide variety of 2-heteroaryl pyrimidines from 2-chloropyrimidyl derivatives in high yields, and is also useful in the preparation of various biaryl derivatives from heteroaryl chlorides.     

Palladium-catalyzed Suzuki–Miyaura cross-coupling reaction of potassium 2-pyridyl trifluoroborate with aryl (heteroaryl) halides

Palladium-catalyzed Suzuki–Miyaura cross-coupling reaction of potassium pyridine-2-trifluoroborates and various aryl (heteroaryl) halides can generate the corresponding desired coupling products with moderate to good yields. It can be carried out under the conditions with ethanol as solvent, Pd(OAc)₂ and SPhos as catalyst system and Na₂CO₃ as a base.     

Gel-entrapped bases: A smart window for the ligand-free Suzuki–Miyaura cross-coupling reaction

A gel-entrapped base has been fabricated by using agarose (biopolymer), and tested in the Suzuki–Miyaura cross-coupling reaction in 95% ethanol. The developed environmentally benign polymer-supported base has low leaching and high stability for the Suzuki–Miyaura cross-coupling reaction to give high yield with green credit.     

Substituted potassium internal vinyltrifluoroborates: preparation and use in Suzuki–Miyaura cross-coupling reactions

A collection of substituted potassium internal vinyltrifluoroborates was prepared and utilized in palladium-catalyzed cross-coupling reactions with aryl and heteroaryl halides. The cross-coupling reactions proceeded readily with Pd(PPh₃)₄ as a catalyst in toluene/H₂O under reflux in the presence of Cs₂CO₃. The process is regiospecific with regard to the internal vinyltrifluoroborate starting material and tolerates a variety of functional groups. This unique collection of substituted internal vinyltrifluoroborates can be readily utilized in research pharmaceutical applications.     

Preparing Pd catalysts based on urea ligand via electrospinning for Suzuki–Miyaura cross-coupling reactions

Pd-catalyzed Suzuki–Miyaura cross-coupling (SMC) reactions are important in chemistry. In this work, using electrospinning technology, we prepared a novel type of composite catalyst with ligand structures such as urea-Pd/PAN (polyacrylonitrile) and used them to catalyze SMC reactions in nontoxic systems and “green” conditions (air atmosphere, low temperature, and short reaction time). This method of preparing hybrid materials is simple and easy to operate. The higher catalytic activity of the catalysts is attributed to active centers with rich electrons transferred from ligands with unique structures, which can decrease the activation energy of the rate-determining step (oxidative addition). In addition, urea-Pd/PAN composite catalysts exhibit higher catalytic performance than those reduced by H₂ because of the smaller size of active species and the more-efficient oxidative addition to Pd⁰–ligand complexes compared to Pd⁰.     

Chemoselective Suzuki–Miyaura cross-coupling reactions of methyl 4-bromo-3-(trifluoromethylsulfonyloxy)-2-naphthoate

Arylated naphthalenes were prepared by Suzuki–Miyaura cross-coupling reactions of methyl 4-bromo-3-(trifluoromethylsulfonyloxy)-2-naphthoate. The reactions proceeded with very good chemoselectivity in favor of the triflate group, due to additive electronic ortho electronic effects.     

Stereoselective synthesis of the insect growth regulator (S)-(+)-hydroprene through Suzuki–Miyaura cross-coupling

A stereoselective synthesis of the insect growth regulator (S)-(+)-hydroprene has been developed in seven steps with 50% overall yield starting from an easily available bromoester. Through using the Suzuki–Miyaura cross-coupling as the key C_sp2–C_sp2 bond forming step, high level of stereocontrol of the C2–C3 olefin is achieved.     

Efficient synthesis of neurotrophic honokiol using Suzuki–Miyaura reactions

Efficient synthesis of honokiol (1) was accomplished using two kinds of Suzuki–Miyaura reactions. The first Suzuki–Miyaura reaction was employed to couple 2-bromophenol (6) with 4-hydroxyphenylboronic acid (5), giving rise to biphenol 4, and the second coupling was used to introduce allyl groups at 5- and 3′-positions of honokiol. The total synthesis of 1 was completed in 74% yield over five steps from 6, or in 83% yield over four steps from biphenol 4.     

Chemoselective Suzuki–Miyaura reactions of 4-trifluoromethylsulfonyloxy-6-bromocoumarin

Suzuki–Miyaura reactions of 4-trifluoromethylsulfonyloxy-6-bromocoumarin provide a convenient access to arylated coumarins. The reactions proceed with excellent chemoselectivity in favour of position 4.     

Palladium-catalysed Suzuki–Miyaura coupling reactions of Bromhexine and Ambroxol

The Suzuki–Miyaura coupling reaction was applied for the synthesis of biologically relevant derivatives of known mucolytic agents Bromhexine and Ambroxol. Using commercially available electron-rich and electron-poor arylboronic acids the desired products are obtained in moderate to high yields (42–81%).     

Suzuki–Miyaura Cross-Coupling of Bromotryptophan Derivatives at Ambient Temperature

Mild reaction conditions are highly desirable for bio-orthogonal side chain derivatizations of amino acids, peptides or proteins due to the sensitivity of these substrates. Transition metal catalysed cross-couplings such as Suzuki–Miyaura reactions are highly versatile, but usually require unfavourable reaction conditions, in particular, when applied with aryl bromides. Ligand-free solvent-stabilised Pd-nanoparticles represent an efficient and sustainable alternative to conventional phosphine-based catalysts, because the cross-coupling can be performed at considerably lower temperature. We report on the application of such a highly reactive heterogeneous catalyst for the Suzuki–Miyaura cross-coupling of brominated tryptophan derivatives. The solvent-stabilised Pd-nanoparticles are even more efficient than the literature-known ADHP-Pd precatalyst. Interestingly, the latter also leads to the formation of quasi-homogeneous Pd-nanoparticles as the catalytic species. One advantage of our approach is the compatibility with aqueous and aerobic conditions at near-ambient temperatures and short reaction times of only 2 h. The influence of different N^α-protecting groups, boronic acids as well as the impact of different amino acid side chains in bromotryptophan-containing peptides has been studied. Notably, a surprising acceleration of the catalysis was observed when palladium-coordinating side chains were present in proximal positions.