Suzuki-Miyaura cross-coupling reaction on copper-trans-A(2)B corroles with excellent functional group tolerance

The palladium-catalyzed Suzuki-Miyaura cross-coupling reaction has been investigated on meso-substituted trans-A₂B-corrole using tailored Pd-catalyst systems.We present the first examples of Suzuki-Miyaura cross-coupling reactions on meso-substituted trans-A₂B-corrole derivatives with neutral, sterically hindered, inactivated and heteroaromatic boronic acids and esters, alkenylboronic acids, as well as quickly deboronating aryl boronic acids and benzo-condensated five membered heterocyclic boronic acids. In addition, we established a high-yield procedure for the Suzuki-Miyaura cross-coupling reaction of corroles with neutral boronic acids.Due to the lability of the free-base corrole macrocycles, functionalization of the corrole periphery was performed with the corresponding Cu-metallated species. meso-Substituted trans-A₂B-corrole can hence be regarded as highly versatile platform towards more sophisticated corrole systems.X-ray structure analysis of a functionalized meso-substituted trans-A₂B copper corrole exhibited the typical features of such a Cu-complex: short N-Cu distances and a saddled corrole configuration.Moreover, we observed a sensitivity of the formal oxidation state of the coordinated copper ions towards Suzuki-Miyaura cross-coupling reaction conditions, where the central copper(III) ion approaches the characteristic features of a copper(II) species. This redox behaviour was examined by UV/vis absorption spectra, nuclear magnetic resonance (NMR) experiments and time-dependent density functional theoretical calculations.     

Chelation‐Assisted Cross‐Coupling of Anilines through In Situ Activation as Diazonium Salts with Boronic Acids under Ligand‐, Base‐, and Salt‐Free Conditions

We describe the coupling of anilines with aryl boronic acids, under ligand‐, base‐, and salt‐free conditions at room temperature. This new reaction proceeds through the formation of an aryl palladium alkoxo complex, which allows the transmetalation step with aryl boronic acids without any external base. Importantly, this sustainable procedure generates only environmentally friendly byproducts such as tBuOH, H₂O, N₂, and B(OH)₃. The reaction mechanism has been deeply investigated through experimental and theoretical studies.     

Lithium aminoborohydrides 17. Palladium catalyzed borylation of aryl iodides, bromides, and triflates with diisopropylaminoborane prepared from lithium diisopropylaminoborohydride

The Alcaraz-Vaultier borylation of aryl halides and triflates is reported utilizing diisopropylaminoborane (BH₂N(ⁱPr)₂) prepared from the corresponding lithium aminoborohydride (LAB reagent). BH₂N(ⁱPr)₂, prepared by reacting lithium diisopropylaminoborohydride with trimethylsilyl chloride, provided the most consistent isolated yields from this reaction. Catalytic amounts of palladium dichloride produced the highest yields from aryl iodides, while catalytic tris(dibenzylideneacetone)dipalladium(chloroform) provided the best yields for aryl bromides and triflates. This route to boronic acids is mild enough to tolerate various functionalities and for the first time employs aryl triflates as substrates for the Alcaraz-Vaultier borylation. In addition, it was found that both boronic acid and ester compounds could be isolated from the reaction mixture utilizing simple work-up procedures. Treatment of the reaction intermediate with an acid/base work-up provided the corresponding boronic acid, while treating the same intermediate with a diol, such as neopentyl glycol, afforded the corresponding boronic ester.     

A convenient method for preparing aromatic ketones from acyl chlorides and arylboronic acids via Suzuki-Miyaura type coupling reaction

Aromatic ketones are synthesized efficiently via palladium-catalyzed cross-coupling reaction of boronic acids with acyl chlorides in the presence of K₃PO₄ hydrate in toluene. This allows the use of aliphatic acyl chlorides as the starting material. Hydrated water plays a significant role as an H₂O source to activate the catalytic system.     

Study on the Regioselectivity of Rhodium-Catalyzed Ring Opening Reactions of C1-Substituted 7-Oxabenzonorbornadienes with Boronic Acids

An optimized condition for the rhodium-catalyzed ring-opening reaction of C₁-substituted oxabicyclic alkenes with aryl boronic acids was developed and the effect of aryl boronic acid as well as the effect of C₁ substitution on the oxabicyclic alkenes was studied. Aryl boronic acids carrying electron-donating substituents provided the ring-opened products in excellent yields regardless of the position, while electron-withdrawing substituents were more susceptible to steric interactions. Although two different regioisomers are possible, all the rhodium-catalyzed ring-opening reactions of C₁ substituted oxabicyclic alkenes studied with aryl boronic acids were found to be highly regioselective, giving single regioisomers in all cases.     

Reaction of Hydantoin with Boronic Acids

We have examined the reaction of hydantoin (=imidazolidine‐2,4‐dione) with (formylphenyl)boronic acids, where the addition of a boronic acid group is hoped to increase bioactivities. Addition of (2‐formylphenyl)boronic acid to hydantoin gave an unexpected azaborine compound, which presumably arises by initial formation of the (phenylmethylidene)hydantoin, with subsequent loss of H₂O to give the cyclized product. Reactions of (3‐formylphenyl)‐ and (4‐formylphenyl)boronic acids with hydantoin gave the corresponding [(Z)‐phenylmethylidene]hydantoins in good‐to‐excellent yields. Attempts to use (3‐formylthiophen‐2‐yl)boronic acid gave a product where the boronic acid group has been cleaved.     

A Universal Procedure for the [18F]Trifluoromethylation of Aryl Iodides and Aryl Boronic Acids with Highly Improved Specific Activity

Herein, we describe a valuable method for the introduction of the [¹⁸F]CF₃ group into arenes with highly improved specific activity by the reaction of [¹⁸F]trifluoromethane with aryl iodides or aryl boronic acids. This [¹⁸F]trifluoromethylation reaction is the first to be described in which the [¹⁸F]CF₃ products are generated in actual trace amounts and can therefore effectively be used as PET tracers. The method shows broad scope with respect to possible aryl iodide and aryl boronic acid substrates, as well as good to excellent conversion. In particular, the [¹⁸F]trifluoromethylation of boronic acids was found to outperform [¹⁸F]trifluoromethylation reactions of halogenated aryl precursors with regard to conversion, reaction conditions, and kinetics.     

Carbene adduct of cyclopalladated ferrocenylimine: Efficient catalyst for the Suzuki coupling of sterically hindered aryl chlorides with a weaker base and low catalyst loading

One-pot synthesis of the N,N′-bis(2,6-diisopropylphenyl)imidazol-2-ylidene (IPr) adduct of cyclopalladated ferrocenylimine complex 1 has been described. This complex has been successfully applied to Suzuki coupling reaction. Various aryl chlorides and boronic acids can be coupled efficiently with a mild base K₃PO₄·7H₂O and low catalyst loadings. This system has been proven to be compatible with the sterically hindered aryl chlorides and some boronic acids leading to form di- and tri-ortho-substituted biaryls 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.     

A comparison of the structure and bonding in the aliphatic boronic R–B(OH)<Subscript>2</Subscript> and borinic R–BH(OH) acids (R=H; NH<Subscript>2</Subscript>, OH,and F): a computational investigation

Boronic acids, R–B(OH)₂, play an important role in synthetic, biological, medicinal, and materials chemistry. This investigation compares the structure and bonding surrounding the boron atoms in the simple aliphatic boronic acids, R–B(OH)₂ (R=H; NH₂, OH, and F), and the analogous borinic acids, R–BH(OH). Geometry optimizations were performed using second-order Møller–Plesset perturbation theory (MP2) with the Dunning–Woon aug-cc-pVTZ, aug-cc-pVQZ, and aug-cc-pV5Z basis sets; single-point CCSD(FC)/aug-cc-pVTZ//MP2(FC)/aug-cc-pVTZ level calculations were used to generate a QCI density for natural bond orbital analyses of the bonding. The optimized boron–oxygen bond lengths for the X–B–O_t–H trans-branch of the endo-exo form of the boronic acids and for the X–B–O–H cis-branch of the boronic and borinic acids (X=N, O, and F, respectively) decrease as the electronegativity of X increases. The boron–oxygen bond lengths are generally longer in the endo-exo or anti forms of the boronic acids than in the corresponding borinic acids. NBO analyses suggest the boron–oxygen bond in H₂BOH is a double bond; the boron–oxygen bonding in the remaining boronic and borinic acids in this study has a significant contribution from dative pπ–pπ bonding. Values for Δ\({\text{H}}_{298}^{0}\) for the highly balanced reaction, R–B(OH)₂ + R–BH₂ → 2 R–BH(OH), suggest that the bonding surrounding the boron atom is stronger in the borinic acid than in the corresponding boronic acid.     

The Discovery of a Palladium(II)‐Initiated Borono‐Catellani Reaction

Reported is a novel palladium(II)‐initiated Catellani‐type reaction that utilizes widely accessible aryl boronic acids as the substrates instead of aryl halides, thereby greatly expanding the existing scope of this powerful transformation. This borono‐Catellani reaction was promoted by cooperative catalysis between Pd(OAc)₂ and the inexpensive 5‐norbornene‐2‐carbonitrile. Practicality is the striking feature of the reaction: it is run open to air at ambient temperature and no phosphine ligand is needed. This mild, chemoselective, and scalable protocol is compatible with a large range of readily available functionalized aryl boronic acids and bromides, as well as terminating olefins (50 examples, 39–97 % yields). Moreover, the orthogonal reactivity between the borono‐Catellani and classical Catellani reaction was demonstrated. This work is expected to open new avenues for developing novel Catellani‐type reactions.     

Hydrogen Peroxide-Responsive Triggers Based on Borinic Acids: Molecular Insights into the Control of Oxidative Rearrangement

Arylborinic acids represent new, efficient, and underexplored hydrogen peroxide-responsive triggers. In contrast to boronic acids, two concomitant oxidative rearrangements are involved in the complete oxidation of these species, which might represent a major limitation for an efficient effector (drug or fluorophore) release. Herein, a comprehensive study of H₂O₂-mediated unsymmetrical arylborinic acid oxidation to investigate the factors that could selectively guide their oxidative rearrangement is described. The o-CF₃ substituent was found to be an excellent directing group allowing a complete regioselectivity on borinic acid models. This result was successfully applied to synthesizing new borinic acid-based fluorogenic probes, which exclusively release the fluorescent moiety upon H₂O₂ treatment. These compounds maintained their superior kinetic properties compared to boronic acids, thus further enhancing the potential of arylborinic acids as valuable new H₂O₂-sensitive triggers.     

Synthesis of N-aryl trifluoromethylarylketoimines by palladium-catalyzed Suzuki coupling reaction of N-aryltrifluoroacetimidoyl chlorides with aryl boronic acids

A highly efficient Suzuki reaction between N-aryltrifluoroacetimidoyl chlorides and aryl boronic acids using Pd(PPh₃)₄ as a catalyst has been developed. This route allows for selective synthesis of N-aryl trifluoromethylarylketoimines in high yields under mild reaction conditions.     

Synthesis and applications of a new palladacycle as a high active catalyst in the Suzuki couplings

The reaction of biphenyl-based phosphine P(o-C₆H₄Me)Ph₂ (1) with Pd(OAc)₂ in toluene affords the air and water stable palladacycle (2) as a binuclear compound which has been characterized by multi-nuclear NMR spectroscopy and elemental analysis as a mixture of cis and trans isomers with relative intensity of 1:3, respectively. This palladacycle is a highly efficient catalyst precursor for the coupling of aryl boronic acids and aryl halides. Both activated and deactivated aryl bromides and chlorides are efficiently coupled in the presence of 2 to furnish the corresponding cross-coupled products in excellent yields, and a wide variety of functional groups are tolerated in aryl halides. This methodology has also been extended for the coupling of bromoarylphosphines and bromoarylphosphine oxides with aryl boronic acids for the generation of hindered corresponding products.     

General and highly efficient fluorinated-N-heterocyclic carbene–based catalysts for the palladium-catalyzed Suzuki–Miyaura reaction

A general and highly efficient trifluoromethylated-N-heterocyclic carbene (NHC)-based catalyst for the palladium-catalyzed Suzuki–Miyaura reaction was reported. In the presence of the catalyst, reactions of non-activated aryl chlorides and triflates with aryl boronic acids occurred at room temperature with good to excellent yields (63–98%). In addition, catalysts generated from a combination of Pd(OAc)₂/imidazolium salt 6a is not only effective for the coupling of heteroaryl boronic acid with aryl halides and heteroaryl halides, but also efficient for coupling of other heteroaryl halides and heteroaryl boronic acids. Finally, the catalyst is highly effective for Suzuki–Miyaura reaction of aryl bromides and chlorides with 0.01–0.1 mol % loading if the temperature was raised at refluxed THF/H₂O.     

Copper(I) 3-Methylsalicylate Mediates the Chan–Lam N-Arylation of Heterocycles

Copper(I) 3-methylsalicylate (CuMeSal) mediates N-arylation reactions between aryl boronic acids and aromatic heterocycles (Chan–Lam coupling) under moderate reaction conditions (K₂CO₃, methanol, 65 °C, in air, 3–5 h). Both electron-rich and electron-deficient aryl boronic acids and a diverse set of N-heterocycles were allowed to react and gave N-arylation products in reasonable yields, which demonstrate the utility of this catalyst.     

Rhodium‐Catalyzed Addition of Aryl Boronic Acids to 2,2‐Disubstituted Malononitriles

β‐Ketonitriles bearing a quaternary carbon at the 2‐position were prepared through Rh‐catalyzed addition of aryl boronic acids to 2,2‐disubstituted malononitriles. In contrast to the previously described transnitrilative cyanation of aryl boronic acids with dialkylmalononitriles, the present reaction avoids retro‐Thorpe collapse of the intermediate addition product through the use of a milder base. The reaction was amenable to a variety of aryl boronic acids and disubstituted malononitriles, providing a diverse array of β‐ketonitriles. The products could be further derivatized to valuable chiral α,α‐disubstituted‐β‐aminonitriles through addition reactions to the corresponding N ‐tert ‐butanesulfinyl imines.     

Cu(OAc)2 promoted Chan–Evans–Lam C–N cross coupling reactions on the N- and N′-nitrogen atoms of sulfonimidamides with aryl boronic acids

We report a highly efficient and mild protocol for Chan–Evans–Lam C–N cross coupling of sulfonimidamides and aryl boronic acids using Cu(OAc)₂ as mediator, triethylamine (TEA) as base and acetonitrile as solvent. The reaction proceeds at room temperature and provides high to excellent yields for a variety of boronic acids, allowing N-arylation of both N-protected (N-amine nitrogen) and N-deprotected (N′-imine nitrogen) sulfonimidamides.     

Nickel(II)-catalyzed addition reaction of arylboronic acids to isatins

A Ni-catalyzed addition of arylboronic acids to isatins was first developed. The reaction, driven by Ni(acac)₂ and dppp as the phosphine ligand, gave 3-aryl-3-hydroxy-2-oxindoles in up to 97% yield. Scopes of benzyl-protected isatins and arylboronic acids were examined. Substituted phenylboronic acids along with fused-ring and heterocyclic boronic acids reacted with isatins smoothly. Preliminary asymmetric catalysis was investigated as well, showing moderate enantioselectivity. The mechanism was also described.     

Rhodium-Catalyzed Addition of Aryl Boronic Acids to 2,2-Disubstituted Malononitriles

β-Ketonitriles bearing a quaternary carbon at the 2-position were prepared through Rh-catalyzed addition of aryl boronic acids to 2,2-disubstituted malononitriles. In contrast to the previously described transnitrilative cyanation of aryl boronic acids with dialkylmalononitriles, the present reaction avoids retro-Thorpe collapse of the intermediate addition product through the use of a milder base. The reaction was amenable to a variety of aryl boronic acids and disubstituted malononitriles, providing a diverse array of β-ketonitriles. The products could be further derivatized to valuable chiral α,α-disubstituted-β-aminonitriles through addition reactions to the corresponding N-tert-butanesulfinyl imines.