Highly Selective Allylborations of Aldehydes Using α,α‐Disubstituted Allylic Pinacol Boronic Esters

α,α‐Disubstituted allylic pinacol boronic esters undergo highly selective allylborations of aldehydes to give tetrasubstituted homoallylic alcohols with exceptional levels of anti‐Z‐selectivity (>20:1). The scope of the reaction includes both acyclic and cyclic allylic boronic esters which lead to acyclic and exocyclic tetrasubstituted homoallylic alcohols. The use of β‐borylated allylic boronic esters gave fully substituted alkenes bearing a boronic ester which underwent further cross‐coupling enabling a highly modular and stereoselective approach to the synthesis of diaryl tetrasubstituted alkenes. Computational analysis revealed the origin of the remarkable selectivity observed.     

Visible‐Light‐Mediated Chan–Lam Coupling Reactions of Aryl Boronic Acids and Aniline Derivatives

The copper(II)‐catalyzed aerobic oxidative coupling reaction between aryl boronic acids and aniline derivatives was found to be improved significantly under visible‐light‐mediated photoredox catalysis. The substrate scope of this oxidative Chan–Lam reaction was thus expanded to include electron‐deficient aryl boronic acids as viable starting materials.     

Direct Cross‐Couplings of Propargylic Diols

[Pd(PPh₃)₄] catalyzes a Suzuki–Miyaura‐like twofold cross‐coupling sequence between underivatized propargylic diols and either aryl or alkenyl boronic acids to furnish highly substituted 1,3‐dienes. Thus, 2,3‐diaryl‐1,3‐butadienes and their dialkenic congeners ([4]dendralenes) are delivered in a (pseudo)halogen‐free, single‐step synthesis which supersedes existing methods. Allenols are also readily formed. Treatment of these single‐ and twofold cross‐coupled products with acid leads to remarkably short syntheses of highly‐substituted benzofulvenes and aryl indenes, respectively.     

Enantiospecific Synthesis of ortho‐Substituted 1,1‐Diarylalkanes by a 1,2‐Metalate Rearrangement/anti‐SN2′ Elimination/Rearomatizing Allylic Suzuki–Miyaura Reaction Sequence

The one‐pot sequential coupling of benzylamines, boronic esters, and aryl iodides has been investigated. In the presence of an N‐activator, the boronate complex formed from an ortho‐lithiated benzylamine and a boronic ester undergoes stereospecific 1,2‐metalate rearrangement/anti‐S_N2′ elimination to form a dearomatized tertiary boronic ester. Treatment with an aryl iodide under palladium catalysis leads to rearomatizing γ‐selective allylic Suzuki–Miyaura cross‐coupling to generate 1,1‐diarylalkanes. When enantioenriched α‐substituted benzylamines are employed, the corresponding 1,1‐diarylalkanes are formed with high stereospecificity.     

Decarboxylative Conjunctive Cross‐coupling of Vinyl Boronic Esters using Metallaphotoredox Catalysis

The synthesis of complex alkyl boronic esters through conjunctive cross‐coupling of vinyl boronic esters with carboxylic acids and aryl iodides is described. The reaction proceeds under mild metallaphotoredox conditions and involves an unprecedented decarboxylative radical addition/cross‐coupling cascade of vinyl boronic esters. Excellent functional‐group tolerance is displayed, and application of a range of carboxylic acids, including secondary α‐amino acids, and aryl iodides provides efficient access to highly functionalized alkyl boronic esters. The decarboxylative conjunctive cross‐coupling was also applied to the synthesis of sedum alkaloids.     

Dimeric Manganese‐Catalyzed Hydroarylation and Hydroalkenylation of Unsaturated Amides

An unprecedented Mn(I)‐catalyzed selective hydroarylation and hydroalkenylation of unsaturated amides with commercially available organic boronic acids is reported. Alkenyl boronic acids have been successfully employed for the first time in Mn(I)‐catalyzed carbon–carbon bond formation. A wide array of β‐alkenylated amide products can be obtained in moderate to good yields, which offers practical access to five‐ and six‐membered lactams. This protocol has predictable regio‐ and chemoselectivity, excellent functional group compatibility and ease of operation in air, representing a significant step‐forward towards manganese‐catalyzed C?C coupling.     

Pd(0)‐Catalyzed Cu(I)‐Thiophene‐2‐carboxylate‐mediated Cross‐Coupling of Heteroaromatic Thioethers and Boronic Acids—First Liebeskind–Srogl Reaction in Water

The first example of a Liebeskind–Srogl cross‐coupling reaction in water as sole reaction solvent is reported. 2‐(Methylthio)pyridine and 2‐(methylthio)benzothiazole were reacted in the presence of a Pd(0) catalyst and copper(I) thiophene‐2‐carboxylate with a series of arylboronic acids. These cross coupling reactions in water proceeded well with electron‐rich boronic acids and gave comparable yields to literature examples using organic solvents. Electron‐poor boronic acids gave somewhat lower yields in aqueous medium.     

Regioselective Transition‐Metal‐Free Allyl–Allyl Cross‐Couplings

Readily prepared allylic zinc halides undergo S_N2‐type substitutions with allylic bromides in a 1:1 mixture of THF and DMPU providing 1,5‐dienes regioselectively. The allylic zinc species reacts at the most branched end (γ‐position) of the allylic system furnishing exclusively γ,α′‐allyl–allyl cross‐coupling products. Remarkably, the double bond stereochemistry of the allylic halide is maintained during the cross‐coupling process. Also several functional groups (ester, nitrile) are tolerated. This cross‐coupling of allylic zinc reagents can be extended to propargylic and benzylic halides. DFT calculations show the importance of lithium chloride in this substitution.     

A Four‐Component Reaction for the Synthesis of Dioxadiazaborocines

A four‐component reaction for the synthesis of heterocyclic boronates is reported. Readily available hydrazides, α‐hydroxy aldehydes, and two orthogonally reactive boronic acids are combined in a single step to give structurally distinct bicyclic boronates, termed dioxadiazaborocines (DODA borocines). In this remarkable process, one boronic acid reacts as a carbon nucleophile and the other as a boron electrophile to provide enantio‐ and diastereomerically pure heterocyclic boronates with multiple stereocenters in high yields.     

Nickel‐Catalyzed Cross‐Coupling of Redox‐Active Esters with Boronic Acids

A transformation analogous in simplicity and functional group tolerance to the venerable Suzuki cross‐coupling between alkyl‐carboxylic acids and boronic acids is described. This Ni‐catalyzed reaction relies upon the activation of alkyl carboxylic acids as their redox‐active ester derivatives, specifically N‐hydroxy‐tetrachlorophthalimide (TCNHPI), and proceeds in a practical and scalable fashion. The inexpensive nature of the reaction components (NiCl₂?6 H₂O—$9.5 mol^?1, Et₃N) coupled to the virtually unlimited commercial catalog of available starting materials bodes well for its rapid adoption.     

Direct Synthesis of Highly Substituted Pyrroles and Dihydropyrroles Using Linear Selective Hydroacylation Reactions

Rhodium(I) catalysts incorporating small bite‐angle diphosphine ligands, such as (Cy₂P)₂NMe or bis(diphenylphosphino)methane (dppm), are effective at catalysing the union of aldehydes and propargylic amines to deliver the linear hydroacylation adducts in good yields and with high selectivities. In situ treatment of the hydroacylation adducts with p‐TSA triggers a dehydrative cyclisation to provide the corresponding pyrroles. The use of allylic amines, in place of the propargylic substrates, delivers functionalised dihydropyrroles. The hydroacylation reactions can also be combined in a cascade process with a Rh^I‐catalysed Suzuki‐type coupling employing aryl boronic acids, providing a three‐component assembly of highly substituted pyrroles.     

Sequential hydrocarbon functionalization: allylic C-H oxidation/vinylic C-H arylation

A Pd(II)/sulfoxide-catalyzed sequential allylic C-H oxidation/vinylic C-H arylation of alpha-olefins to furnish E-arylated allylic esters in high regio- and E:Z selectivities (>20:1) is reported. The broad scope of this method with respect to the alpha-olefin, carboxylic acid, and aryl boronic acid enables the rapid assembly of densely functionalized fragments for complex molecule synthesis from cheap, abundant hydrocarbon starting materials. The Pd(II)/sulfoxide-catalyzed vinylic C-H arylation of electronically unbiased olefins with aryl boronic acids proceeds under oxidative, acidic conditions and mild temperatures (room temperature to 45 degrees C).     

First comprehensive investigation of Suzuki couplings of alkenyl nonaflates with aryl and alkenyl boronic acid derivatives by using classical conditions and microwave heating

Alkenyl nonaflates (nonafluorobutanesulfonates) are excellent substrates in a variety of palladium-catalysed coupling reactions. We herein demonstrate that bicyclic nonaflates generated from 8-heterobicyclo[3.2.1]octan-3-one derivatives can be coupled with aryl or alkenyl boronic acids in a very efficient manner. The resulting densely functionalised bicyclic skeletons are highly suitable for further synthetic elaboration. The thermal Suzuki couplings provided the expected products in moderate to good yields. Microwave (MW) irradiation dramatically shortened reaction times and gave superior results. Bisboronic ester 19 was also coupled with bicyclic nonaflates, for example, with 14, and double Suzuki-coupling products, such as 22, were isolated in good yields. We demonstrated the great synthetic potential of aryl-substituted 8-heterobicyclo[3.2.1]octene derivatives, such as 15, by the stereoselective conversion of this compound into highly substituted furanose 31 or substituted pyran derivative 33, which were obtained in short and efficient reaction sequences.     

Rhodium‐Catalyzed Transnitrilation of Aryl Boronic Acids with Dimethylmalononitrile

An efficient transnitrilation of aryl boronic acids with dimethylmalononitrile (DMMN) is described. This rhodium‐catalyzed electrophilic cyanation presents a novel approach to prepare aryl nitriles by using a carbon‐bound cyanating reagent which undergoes cross‐coupling with the aryl boronic acid. The reaction expands the degree of functional‐group compatibility exhibited by the transnitrilation of aryl Grignard and aryllithium reagents. A variety of aryl boronic acid derivatives and dialkylmalononitriles were amenable to the transnitrilation.     

Rational Design of an Iron‐Based Catalyst for Suzuki–Miyaura Cross‐Couplings Involving Heteroaromatic Boronic Esters and Tertiary Alkyl Electrophiles

Suzuki–Miyaura cross‐coupling reactions between a variety of alkyl halides and unactivated aryl boronic esters using a rationally designed iron‐based catalyst supported by β‐diketiminate ligands are described. High catalyst activity resulted in a broad substrate scope that included tertiary alkyl halides and heteroaromatic boronic esters. Mechanistic experiments revealed that the iron‐based catalyst benefited from the propensity for β‐diketiminate ligands to support low‐coordinate and highly reducing iron amide intermediates, which are very efficient for effecting the transmetalation step required for the Suzuki–Miyaura cross‐coupling reaction.     

Novel palladium nanoparticles supported on β‐cyclodextrin@graphene oxide as magnetically recyclable catalyst for Suzuki–Miyaura cross‐coupling reaction with two different approaches in bio‐based solvents

A novel nanocatalyst was designed and prepared. Initially, the surface of magnetic graphene oxide (M‐GO) was modified using thionyl chloride, tris(hydroxymethyl)aminomethane and acryloyl chloride as linkers which provide reactive C═C bonds for the polymerization of vinylic monomers. Separately, β‐cyclodextrin (β‐CD) was treated with acryloyl chloride to provide a modified β‐CD. Then, in the presence methylenebisacrylamide as a cross‐linker, monomers of modified β‐CD and acrylamide were polymerized on the surface of the pre‐prepared M‐GO. Finally, palladium acetate and sodium borohydride were added to this composite to afford supported palladium nanoparticles. This fabricated nanocomposite was fully characterized using various techniques. The efficiency of this easily separable and reusable heterogeneous catalyst was successfully examined in Suzuki–Miyaura cross‐coupling reactions of aryl halides and boronic acid as well as in modified Suzuki–Miyaura cross‐coupling reactions of N‐acylsuccinimides and boronic acid in green media. The results showed that the nanocatalyst was efficient in coupling reactions for direct formation of the corresponding biphenyl as well as benzophenone derivatives in green media based on bio‐based solvents. In addition, the nanocatalyst was easily separable, using an external magnet, and could be reused several times without significant loss of activity under the optimum reaction conditions.     

Boronic Acids as Bioorthogonal Probes for Site‐Selective Labeling of Proteins

Over the past two decades, bioorthogonal chemistry has become a preferred tool to achieve site‐selective modifications of proteins. However, there are only a handful of commonly applied bioorthogonal reactions and they display some limitations, such as slow rates, use of unstable or cytotoxic reagents, and side reactions. Hence, there is significant interest in expanding the bioorthogonal chemistry toolbox. In this regard, boronic acids have recently been introduced in bioorthogonal chemistry and are exploited in three different strategies: 1) boronic ester formation between a boronic acid and a 1,2‐cis diol; 2) iminoboronate formation between 2‐acetyl/formyl‐arylboronic acids and hydrazine/hydroxylamine/semicarbazide derivatives; 3) use of boronic acids as transient groups in a Suzuki–Miyaura cross‐coupling or other reactions that leave the boronyl group off the conjugation product. In this Review, we summarize progress made in the use of boronic acids in bioorthogonal chemistry to enable site‐selective labeling of proteins and compare these methods with the most commonly utilized bioorthogonal reactions.     

A Highly Efficient Copper‐Mediated Radioiodination Approach Using Aryl Boronic Acids

A convenient and quantitative radioiodination method by copper‐mediated cross‐coupling of aryl boronic acids was developed. The mild labeling conditions, ready availability of the boronic acid substrate, simple operation, broad functional group tolerance and excellent radiochemical yield (RCY) make this a practical strategy for radioiodine labeling without further purification.     

Enantioselective Rhodium‐Catalyzed Dearomative Arylation or Alkenylation of Quinolinium Salts

A highly enantioselective rhodium(I)‐catalyzed dearomative arylation or alkenylation of easily available N‐alkylquinolinium salts is reported, thus providing an effective and practical approach to the synthesis of dihydroquinolines in up to 99 % ee. This reaction tolerates a wide range of functional groups with respect to both the organic boronic acids and the quinoline starting materials. Moreover, the synthetic utility of this protocol is demonstrated in the formal asymmetric synthesis of bioactive tetrahydroquinoline and the total syntheses of (?)‐angustureine and (+)‐cuspareine.     

Palladium‐Catalyzed/Norbornene‐Mediated CH Activation/ N‐Tosylhydrazone Insertion Reaction: A Route to Highly Functionalized Vinylarenes

A straightforward method for the synthesis of highly functionalized vinylarenes through palladium‐catalyzed, norbornene‐mediated C?H activation/carbene migratory insertion is described. Extension to a one‐pot procedure is also developed. Furthermore, this method can also be used to generate polysubstituted bicyclic molecules. The reaction proceeds under mild conditions to give the products in satisfactory yields using readily available starting materials. This is a Catellani–Lautens reaction that incorporates different types of coupling partners. Additionally, this reaction is the first to demonstrate the possibility of combining Pd‐catalyzed insertion of diazo compounds and Pd‐catalyzed C?H activation.