Arylboronic Pinacol Research Articles

Effect of Pyridine Addition on the Efficiency of Copper‐Mediated Radiofluorination of Aryl Pinacol Boronates

AbstractThe rise of the transition‐metal‐mediated and/or catalyzed radiofluorination reactions has led us to investigate possibilities for the improvement of the radiolabeling yields of pinacol esters of arylboronic acids (arylBPin) in the presence of Cu(OTf)2(py)4. Addition of small amounts pyridine to the reaction medium with DMF as a solvent and [18F]F−/K222Cs+complex as [18F]fluoride source was shown to have a significant positive effect on the radiofluorination yields. The effect was investigated in depth using 4‐biphenylboronic acid pinacol ester as a model compound, with up to 20 % increase in radiochemical conversion observed at optimized conditions. Maximum effect was observed at pyridine‐to‐catalyst ratio of 30:1. The findings were applied to a representative electron‐rich ring systems that are traditionally difficult or impossible to radiolabel with nucleophilic fluoride, leading to products such as 2‐[18F]fluoroanisole and protected 4‐L‐[18F]fluorophenylalanine. Given the ever‐present pressure to develop new methods for introduction of fluorine‐18 into various substrates to facilitate easy and robust production of clinically‐relevant radiotracers for PET imaging we believe our findings can be of significant practical interest for radiofluorination of ortho‐substituted substrates in particular.

Enantioselective Construction of Trifluoromethoxylated Stereogenic Centers by a Nickel‐Catalyzed Asymmetric Suzuki–Miyaura Coupling of Secondary Benzyl Bromides

Trifluoromethoxy-substituted stereogenic centers can be constructed with high enantioselectivity by a nickel-catalyzed Suzuki-Miyaura coupling of readily available α-bromobenzyl trifluoromethyl ethers with a variety of aryl pinacol boronates. The coupling proceeds under mild reaction conditions, and a variety of common functional groups, such as fluoride, chloride, bromide, ester, enolizable ketone, nitro, cyano, amino, and vinyl moieties, were well tolerated. Furthermore, the reaction can be easily scaled up to gram quantities without a decrease in enantioselectivity.

Enantioselective Construction of Trifluoromethoxylated Stereogenic Centers by a Nickel‐Catalyzed Asymmetric Suzuki–Miyaura Coupling of Secondary Benzyl Bromides

AbstractTrifluoromethoxy‐substituted stereogenic centers can be constructed with high enantioselectivity by a nickel‐catalyzed Suzuki–Miyaura coupling of readily available α‐bromobenzyl trifluoromethyl ethers with a variety of aryl pinacol boronates. The coupling proceeds under mild reaction conditions, and a variety of common functional groups, such as fluoride, chloride, bromide, ester, enolizable ketone, nitro, cyano, amino, and vinyl moieties, were well tolerated. Furthermore, the reaction can be easily scaled up to gram quantities without a decrease in enantioselectivity.

A palladium-catalyzed oxidative cross-coupling reaction between aryl pinacol boronates and H-phosphonates in ethanol

The first successful oxidative cross-coupling reaction of aryl phosphorous compounds started from pinacol aryl boronic esters is reported.

Synthesis of N-(6-Arylbenzo[d]thiazole-2-acetamide Derivatives and Their Biological Activities: An Experimental and Computational Approach.

A new series of N-(6-arylbenzo[d]thiazol-2-yl)acetamides were synthesized by C-C coupling methodology in the presence of Pd(0) using various aryl boronic pinacol ester/acids. The newly synthesized compounds were evaluated for various biological activities like antioxidant, haemolytic, antibacterial and urease inhibition. In bioassays these compounds were found to have moderate to good activities. Among the tested biological activities screened these compounds displayed the most significant activity for urease inhibition. In urease inhibition, all compounds were found more active than the standard used. The compound N-(6-(p-tolyl)benzo[d]thiazol-2-yl)acetamide was found to be the most active. To understand this urease inhibition, molecular docking studies were performed. The in silico studies showed that these acetamide derivatives bind to the non-metallic active site of the urease enzyme. Structure-activity studies revealed that H-bonding of compounds with the enzyme is important for its inhibition.

ChemInform Abstract: Preparation and Reactions of 4‐Iodobutyl Pinacolborate. Synthesis of Substituted Alkyl and Aryl Pinacolboronates via 4‐Iodobutyl Pinacolborate Utilizing Tetrahydrofuran as the Leaving Group.

AbstractThe mild method offers significant improvement compared to previous procedures in terms of operational simplicity as well as costs and environmental impact of the reagents used.

Copper-mediated aromatic radiofluorination revisited: efficient production of PET tracers on a preparative scale.

Two novel methods for copper-mediated aromatic nucleophilic radiofluorination were recently reported. Evaluation of these methods reveals that, although both are efficient in small-scale experiments, they are inoperative for the production of positron emission tomography (PET) tracers. Since high base content turned out to be responsible for low radiochemical conversions, a "low base" protocol has been developed which affords (18)F-labeled arenes from diaryliodonium salts and aryl pinacol boronates in reasonable yields. Furthermore, implementation of our "minimalist" approach to the copper-mediated [(18)F]-fluorination of (mesityl)(aryl)iodonium salts allows the preparation of (18)F-labeled arenes in excellent RCCs. The novel radiofluorination method circumvents time-consuming azeotropic drying and avoids the utilization of base and other additives, such as cryptands. Furthermore, this procedure enables the production of clinically relevant PET tracers; [(18)F]FDA, 4-[(18)F]FPhe, and [(18)F]DAA1106 are obtained in good isolated radiochemical yields. Additionally, [(18)F]DAA1106 has been evaluated in a rat stroke model and demonstrates excellent potential for visualization of translocator protein 18 kDa overexpression associated with neuroinflammation after ischemic stroke.

ChemInform Abstract: Metal‐Free Halogenation of Arylboronate with N‐Halosuccinimide

Abstract20 examples

Preparation and reactions of 4-iodobutyl pinacolborate. Synthesis of substituted alkyl and aryl pinacolboronates via 4-iodobutyl pinacolborate utilizing tetrahydrofuran as the leaving group

Iodine reacts with 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (HBpin), under ambient reaction conditions in THF, to form the iodoalkylborate species 2-(4-iodobutoxy)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (4-IboxBpin). Apparently, one-half equivalent of I2 reacts with HBpin to form IBpin in pentanes, which in turn cleaves THF to form the 4-IboxBpin. Alkyl and aryl Grignard reagents, prepared under Barbier conditions, then react with 4-IboxBpin to form the corresponding alkyl and aryl pinacolboronates while reforming and liberating THF as the leaving group.

Metal-free halogenation of arylboronate with N-halosuccinimide

Efficient bromination and chlorination of aryl pinacol boronates were accomplished without the addition of metal reagent. The reaction proceeded efficiently with electron-rich arylboronates or heteroarylboronates in DMF or acetonitrile, to afford mono-, di-, or trihalogenated aryl pinacol boronates.

ChemInform Abstract: Suzuki—Miyaura Cross‐Coupling under Solvent‐Free Conditions.

AbstractA solvent‐free protocol for the Pd‐catalyzed coupling of a wide range of aryl bromides and chlorides with pinacol arylboronates is developed to give the corresponding coupling products in excellent yields.

Direct synthesis of arylboronic pinacol esters from arylamines

A Sandmeyer-type transformation of converting aromatic amines into the corresponding arylboronic pinacol esters has been developed.

Suzuki–Miyaura Cross‐Coupling under Solvent‐Free Conditions

AbstractA solvent‐free reaction protocol for Suzuki–Miyaura cross‐couplings was developed. (Hetero)aryl bromides and chlorides are coupled with pinacol arylboronates in high yields. The reaction is catalyzed by conventional bis(triphenylphosphine)palladium(II) chloride [(PPh3)2PdCl2] and/or palladium(II) acetate/SPhos [Pd(OAc)2/SPhos] under air.magnified image

Design and Synthesis of Arylthiophene-2-Carbaldehydes via Suzuki-Miyaura Reactions and Their Biological Evaluation

A series of various novel 4-arylthiophene-2-carbaldehyde compounds were synthesized in moderate to excellent yields via Suzuki-Miyaura cross-coupling with different arylboronic pinacol esters/acids. The synthesized products were screened for their antibacterial, haemolytic, antiurease, and nitric oxide (NO) scavenging capabilities and interestingly, almost all products turned out to have good activities. 3-(5-Formyl-thiophene-3-yl)-5-(trifloromethyl)benzonitrile (2d) revealed excellent antibacterial activity, showing an IC50 value of 29.7 µg/mL against Pseudomonas aeruginosa, compared to the standard drug streptomycin with an IC50 value 35.2 µg/mL and was also found to be the best NO scavenger, with an IC50 value of 45.6 µg/mL. Moreover, 4-(3-chloro-4-fluoro-phenyl)thiophene-2-carbaldehyde (2i) exhibited a superior haemolytic action and an outstanding urease inhibition, showing an IC50 value of 27.1 µg/mL.

ChemInform Abstract: Sterically Controlled Alkylation of Arenes Through Iridium‐Catalyzed C—H Borylation.

AbstractThis publication describes the site‐selective alkylation, allylation, and benzylation of arenes via in‐situ‐generated aryl pinacol boronates.

Direct Amination of Alkyl and Aryl Pinacol Boronates

Direct Amination of Alkyl and Aryl Pinacol Boronates

Direct Stereospecific Amination of Alkyl and Aryl Pinacol Boronates

The direct amination of alkyl and aryl pinacol boronates is accomplished with lithiated methoxyamine. This reaction directly provides aliphatic and aromatic amines, stereospecifically, and without preactivation of the boronate substrate.

ChemInform Abstract: Sandmeyer‐Type Reaction to Pinacol Arylboronates in Water Phase: A Green Borylation Process.

AbstractCopper‐catalyzed cross‐coupling of aryl diazonium salts with diboron (II) proceeds under mild conditions and allows the direct synthesis of arylboronates bearing halogen and acidic substituents.

Comparison of Arylboron-Based Nucleophiles in Ni-Catalyzed Suzuki–Miyaura Cross-Coupling with Aryl Mesylates and Sulfamates

The efficiency of arylboron-based nucleophiles, boronic acid, potassium trifluoroborate, neopentylglycolboronate, and pinacol boronate in nickel-catalyzed Suzuki-Miyaura cross-coupling reactions with the two C-O electrophiles, mesylates, and sulfamates was compared. Arylboronic acid is the most reactive and most atom-economic of the four boron species studied. Arylpotassium trifluoroborate cross-couples efficiently only in the presence of water. In the absence of water, aryl neopentylglycolboronate is more efficient, less expensive, and more atom-economic than aryl pinacolboronate.

Sandmeyer-Type Reaction to Pinacol Arylboronates in Water Phase: A Green Borylation Process

Copper(I)-catalyzed cross-coupling reactions of aryl diazonium salts with bis(pinacolato)diboron can proceed smoothly in the water phase at room temperature to give the corresponding arylboronate esters in good to high yields. The Sandmeyer-type borylation not only provides direct access to arylboronates bearing halo and acidic substituents, but also achieves a green borylation process.