Coupling Of Boronic Acids Research Articles

Chelation enables selectivity control in enantioconvergent Suzuki–Miyaura cross-couplings on acyclic allylic systems

Asymmetric Suzuki–Miyaura cross-couplings with aryl boronic acids and allylic electrophiles are a powerful method to convert racemic mixtures into enantioenriched products. Currently, enantioconvergent allylic arylations are limited to substrates that are symmetrical about the allylic unit, and the absence of strategies to control regio-, E/Z- and enantioselectivity in acyclic allylic systems is a major restriction. Here, using a system capable of either conjugate addition or allylic arylation, we have discovered the structural features and experimental conditions that allow an acyclic system to undergo chemo- and regioselective, enantioconvergent allylic Suzuki–Miyaura-type arylation. A wide variety of boronic acid coupling partners can be used, and both alkyl and aromatic substituents are tolerated on the allylic unit so that a wide variety of structures can be obtained. Preliminary mechanistic studies reveal that the chelating ability of the ester group is crucial to obtaining high regio- and enantioselectivity. Using this method, we were able to synthesize the natural products (S)-curcumene and (S)-4,7-dimethyl-1-tetralone and the clinically used antidepressant sertraline (Zoloft).

Three-component coupling of boronic acids, amines, and carbon disulfide by a heterogeneous catalyst of copper (II) embedded in a highly porous and magnetic Schiff base network of melamine

Three-component coupling of boronic acids, amines, and carbon disulfide by a heterogeneous catalyst of copper (II) embedded in a highly porous and magnetic Schiff base network of melamine

Chemoselective Chan-Lam and reductive nitroarene coupling of boronic acid using an octahedral Ni-DMAP complex as catalyst

An octahedral Ni-DMAP complex has been developed as catalyst for C–N and C–S cross coupling and reductive nitroarene coupling using boronic acid as coupling partner. Reaction of amines, thiols, azides, and tosyl azides with boronic acids could be achieved in presence of 10 mol % of the catalyst in methanol at 80 °C without using extra base. The current protocol is highly selective for primary amines in presence of secondary amines, thiols and phenols. Reductive coupling of a range of nitroarenes and boronic acids was also successfully achieved using the same catalyst.

Rhodium(I)-Catalyzed Defluorinative Coupling of Boronic Acids with Monofluoroalkenes.

We herein describe a highly selective Rh(I)-catalyzed defluorinative coupling of boronic acids with (E)-β-monofluoroacrylates. In contrast to previous methods, the trisubstituted (Z)-alkene products were obtained in excellent dr with an inversion of double bond geometry. Experimental and computational studies established that Rh(I)-facilitated β-F elimination is favored over competing β-H elimination and protodemetalation.

Mechanistic investigation of Rh(i)-catalysed asymmetric Suzuki–Miyaura coupling with racemic allyl halides

Understanding how catalytic asymmetric reactions with racemic starting materials can operate would enable new enantioselective cross-coupling reactions that give chiral products. Here we propose a catalytic cycle for the highly enantioselective Rh(i)-catalysed Suzuki–Miyaura coupling of boronic acids and racemic allyl halides. Natural abundance 13C kinetic isotope effects provide quantitative information about the transition-state structures of two key elementary steps in the catalytic cycle, transmetallation and oxidative addition. Experiments with configurationally stable, deuterium-labelled substrates revealed that oxidative addition can happen via syn- or anti-pathways, which control diastereoselectivity. Density functional theory calculations attribute the extremely high enantioselectivity to reductive elimination from a common Rh complex formed from both allyl halide enantiomers. Our conclusions are supported by analysis of the reaction kinetics. These insights into the sequence of bond-forming steps and their transition-state structures will contribute to our understanding of asymmetric Rh–allyl chemistry and enable the discovery and application of asymmetric reactions with racemic substrates. A major drive in current chemistry research is to develop asymmetric versions of widely used carbon–carbon bond-forming reactions, such as Suzuki-Miyaura cross-couplings. Now, the origins of diastereo- and enantioselectivity in a Rh-catalysed cross-coupling of boronic acid and racemic allyl halides have been established.

Cu-catalyzed C(sp2)-N-bond coupling of boronic acids and cyclic imides.

A general Cu-catalyzed strategy for coupling cyclic imides and alkenylboronic acids by forming C(sp2)-N-bonds is reported. The method enables the practical and mild preparation of (E)-enimides. A large range of cyclic imides are allowed, and di- and tri-substituted alkenylboronic acids can be used. Full retention was observed in the configuration of the alkene double bond in the coupled products. The method is also applicable for preparing N-arylimides, using arylboronic acids as coupling partners. The usefulness of this strategy is exemplified by the convenient derivatization of the chemotherapy medication 5-flurouracil, the nucleoside uridine and the anti-epileptic drug phenytoin.

Significant rate enhancement via potassium pivalate in a Miyaura borylation approach to verinurad

We describe herein the significant rate-enhancing effect of employing potassium pivalate as a base in a Miyaura borylation. The manufacturing route to verinurad currently employs a Suzuki-Miyaura cross-coupling, requiring cryogenic conditions to generate the boronic acid coupling partner. This process has manufacturability challenges including those associated with low temperature operations and thus an alternative Miyaura borylation approach is described. High throughput screening was employed to investigate the effects of various carboxylate bases and their corresponding counterions on reactivity. Our results highlight potassium pivalate as producing exceptional rate acceleration. To the best of our knowledge this base has not previously been reported for use in Miyaura borylations. Diethanolamine transesterification is also reported as a facile and robust boronate isolation protocol. Successful application of this diethanolamine boronate ester in downstream cross-coupling chemistry has demonstrated the potential for this new route in commercial manufacture of verinurad.

Self-Assembly of Catalytically Active Supramolecular Coordination Compounds within Metal-Organic Frameworks.

Supramolecular coordination compounds (SCCs) represent the power of coordination chemistry methodologies to self-assemble discrete architectures with targeted properties. SCCs are generally synthesized in solution, with isolated fully coordinated metal atoms as structural nodes, thus severely limited as metal-based catalysts. Metal-organic frameworks (MOFs) show unique features to act as chemical nanoreactors for the in situ synthesis and stabilization of otherwise not accessible functional species. Here, we present the self-assembly of PdII SCCs within the confined space of a pre-formed MOF (SCCs@MOF) and its post-assembly metalation to give a PdII-AuIII supramolecular assembly, crystallography underpinned. These SCCs@MOFs catalyze the coupling of boronic acids and/or alkynes, representative multi-site metal-catalyzed reactions in which traditional SCCs tend to decompose, and retain their structural integrity as a consequence of the synergetic hybridization between SCCs and MOFs. These results open new avenues in both the synthesis of novel SCCs and their use in heterogeneous metal-based supramolecular catalysis.

Exploiting Coupling of Boronic Acids with Triols for a pH-Dependent "Click-Declick" Chemistry.

Click-like condensation of boronic acids with specifically designed triols (boronate-triol coupling) produces stable diamantane adducts in aqueous medium, which can be controllably cleaved to initial components under acidic conditions or by using boric acid as a chemical trigger. This novel "click-declick" strategy allows for the creation of temporary covalent connections between two or more modular units, which was demonstrated by the synthesis of new fluorophore-labeled natural molecules (peptides, steroids), supramolecular assemblies, modified polymers, boronic acid scavengers, solid-supported organocatalysts, biodegradable COF-like materials, and dynamic combinatorial libraries.

Recent Chemical Biology Approaches for Profiling Cell Surface Sialylation Status.

Sialic acids (SAs) often exist as the terminal sugars of glycans of either glycoproteins or glycolipids on the cell surface and thus are directly involved in biological processes, such as cell-cell, cell-ligand, and cell-pathogen interactions. Cell surface SA expression levels and their linkages are collectively termed cell surface sialylation status, which represent varying cellular states and contribute to the overall functionality of a cell. Accordingly, systemic and specific profiling of the cell surface sialyation status is critical in deciphering the structures and functions of cell surface glycoconjugates and the molecular mechanisms of their underlying biological processes. In recent decades, several advanced chemical biology approaches have been developed to profile the cell surface sialyation status of both in vitro and in vivo samples, including metabolic labeling, direct chemical modification, and boronic acid coupling approaches. Various investigative technologies have also been explored for their unique competence, including fluorescent imaging, flow cytometry, Raman imaging, magnetic resonance imaging (MRI), and matrix-assisted laser desorption ionization imaging mass spectrometry. In particular, the sialylation status of a specific glycoprotein on the cell surface has been investigated. This review highlights the recent advancements in chemical biology approaches for profiling cell surface sialyation status. It is expected that this review will provide researchers different choices for both biological and biomedical research and applications.

PEPPSI-type palladium 1,2,3-triazolin-5-ylidene complexes – Synthesis, structure and catalytic properties in Suzuki-Miyaura coupling

Palladium complexes of the general formula [PdCl2(tzNHC)(pyridine)] bearing a series 1,2,3-triazolin-5-ylidene (tzNHC) ligands were synthesized and characterized by spectroscopic methods and X-ray analysis. Complexes exhibit catalytic activity in the Suzuki-Miyaura coupling of boronic acids with aryl bromides.

Regio- and Stereoselective Nickel-Catalyzed Coupling of Boronic Acids with Allenoates

The Ni(II)-catalyzed cross-coupling of arylboronic acids with allenoates is documented. The high regio- and stereoselectivity of the process enables a wide range of β-aryl β,γ-unsaturated esters to be prepared in good to excellent yields (up to 95%) and high E/Z-selectivity. Additionally, [3+2]-cascade sequence was observed when 2-formylphenylboronic acid was employed.

Synthesis of Highly Substituted 2-Arylindoles via Copper-Catalyzed Coupling of Isocyanides and Arylboronic Acids.

Highly functionalized 2-arylindoles were synthesized from 2-alkenylarylisocyanides and arylboronic acids using a simple, inexpensive copper catalyst. The reaction exhibits excellent functional group tolerance for both the arylisocyanide and boronic acid coupling partners. To avoid the direct handling of the pungent arylisocyanide starting materials, continuous flow chemistry is further demonstrated to provide safe and effective access to 2-arylindoles through in situ dehydration and cyclization of easy-to-handle 2-alkenyl- N-formylanilines.

Catalyst-free Petasis-type reaction: Three-component decarboxylative coupling of boronic acids with proline and salicylaldehyde for the synthesis of alkylaminophenols

A simple method is reported for the synthesis of alkylaminophenols in moderate to good yields via a three-component, catalyst-free decarboxylative coupling of proline with salicylaldehyde and boronic acids.

Coupling of Boronic Acids, 1,3-Enynes and Cyclic Imines

Key words rhodium catalysis - enantioselective nucleophilic allylation - 1,4-rhodium(I) migration - three-component coupling

ChemInform Abstract: 2,5‐Oxyarylation of Furans: Synthesis of Spiroacetals via Palladium‐Catalyzed Aerobic Oxidative Coupling of Boronic Acids with α‐Hydroxyalkylfurans.

AbstractThe scalable protocol is used for a novel transformation of sustainable furans into 2,5‐oxarylated derivatives.

Copper-Mediated Coupling of Boronic Acids, Amines, and Carbon Disulfide: An Approach to Organic Dithiocarbamates

An efficient copper-mediated three-component coupling reaction of boronic acids, amines, and carbon disulfide has been developed, which provides a new approach to a wide range of functionalized dithiocarbamates in good to excellent yields. The present methodology has many advantages, such as mild reaction conditions, easily available substrates, wide substrate scope, and high functional-group tolerance.

Synthesis of Phosphanylferrocenecarboxamides Bearing Guanidinium Substituents and Their Application in the Palladium‐Catalyzed Cross‐Coupling of Boronic Acids with Acyl Chlorides

Phosphanylferrocene donors bearing polar guanidinium substituents, namely acylguanidinium chloride, [Ph2PfcCONHC(NH2)NH2]Cl (1), and amidoguanidinium chloride, [Ph2PfcCONHCH2CH2NHC(NH2)NH2]Cl (2; fc = ferrocene‐1,1′‐diyl), have been prepared and characterized. As functional phosphane donors, they were employed in the synthesis of PdII complexes bearing 2‐[(dimethylamino)methyl‐κN]phenyl‐κC1 (LNC) and η3‐allyl supporting ligands, [(LNC)PdCl(L‐κP)] and [(η3‐C3H5)PdCl(L‐κP)] (L = 1 and 2), respectively. These defined complexes as well as their surrogates generated in situ from the respective palladium(II) precursor and the phosphanylferrocene ligand were evaluated as catalysts for the coupling of boronic acids with acyl chlorides to give ketones in an aqueous biphasic system. The coupling reaction proceeded best with a simple catalyst formed from Pd(OAc)2 and ligand 2, which (at 0.2 mol‐% Pd loading) produced substituted benzophenones from benzoyl chlorides and benzeneboronic acids in very good yields. These yields could then be further improved by a proper choice of the reaction partners. Analogous reactions involving aliphatic substrates generally afforded lower yields.

2,5-Oxyarylation of Furans: Synthesis of Spiroacetals via Palladium-Catalyzed Aerobic Oxidative Coupling of Boronic Acids with α-Hydroxyalkylfurans.

A protocol for the 2,5-oxyarylation of furan rings via Pd-catalyzed aerobic oxidative coupling of boronic acids with α-hydroxyalkylfurans is reported. This protocol provides rapid, green access to diverse biologically interesting and synthetically useful unsaturated spiroacetals from sustainable furan derivatives.

Histidine-Directed Arylation/Alkenylation of Backbone N-H Bonds Mediated by Copper(II).

Chemical modification of proteins and peptides represents a challenge of reaction design as well as an important biological tool. In contrast to side-chain modification, synthetic methods to alter backbone structure are extremely limited. In this communication, copper-mediated backbone N-alkenylation or N-arylation of peptides and proteins by direct modification of natural sequences is described. Histidine residues direct oxidative coupling of boronic acids at the backbone NH of a neighboring amino acid. The mild reaction conditions in common physiological buffers, at ambient temperature, are compatible with proteins and biological systems. This simple reaction demonstrates the potential for directed reactions in complex systems to allow modification of N-H bonds that directly affect polypeptide structure, stability, and function.