Palladium-catalyzed Arylation Research Articles

Regioselective β-Csp3-Arylation of β-Alanine: An Approach for the Exclusive Synthesis of Diverse β-Aryl-β-amino Acids

An approach for the synthesis of a variety of new β-aryl-β-amino acids has been developed via a palladium-catalyzed auxiliary-directed regioselective Csp3-H arylation of the unactivated β-methylene bond of β-alanine. The use of 8-aminoquinoline amide as an auxiliary efficiently directs the desired regioselective β-Csp3-H functionalization. The developed protocol enables the easy and straightforward access to several high-value β-aryl-β-amino acids useful for peptide engineering, starting from inexpensive and readily available β-alanine precursors in moderate to excellent yields.

Ladderization of polystyrene derivatives by palladium-catalyzed polymer direct arylation

Pseudo-ladderized polystyrenes could be obtained in high yield by the palladium-catalyzed polymer direct arylation using poly(2-bromostyrene) as a prepolymer.

Palladium-catalyzed salt-free double decarboxylative aryl allylation.

This report describes a palladium-catalyzed decarboxylative aryl allylation between unactivated benzoic acids and allylic carbonates. This transformation successfully couples a variety of carbonates and benzoic acids in good yield (up to 94%) using 1 mol% palladium. This salt free allyl-arylation proceeds without added base, copper, or silver. The only stoichiometric byproducts are carbon dioxide and tert-butanol.

Palladium-catalyzed decarbonylative Suzuki-Miyaura cross-coupling of amides by carbon-nitrogen bond activation.

Palladium-catalyzed Suzuki-Miyaura cross-coupling or aryl halides is widely employed in the synthesis of many important molecules in synthetic chemistry, including pharmaceuticals, polymers and functional materials. Herein, we disclose the first palladium-catalyzed decarbonylative Suzuki-Miyaura cross-coupling of amides for the synthesis of biaryls through the selective activation of the N-C(O) bond of amides. This new method relies on the precise sequence engineering of the catalytic cycle, wherein decarbonylation occurs prior to the transmetallation step. The reaction is compatible with a wide range of boronic acids and amides, providing valuable biaryls in high yields (>60 examples). DFT studies support a mechanism involving oxidative addition, decarbonylation and transmetallation and provide insight into high N-C(O) bond activation selectivity. Most crucially, the reaction establishes the use of palladium catalysis in the biaryl Suzuki-Miyaura cross-coupling of the amide bond and should enable the design of a wide variety of cross-coupling methods in which palladium rivals the traditional biaryl synthesis from aryl halides and pseudohalides.

Synthesis of π-conjugated network polymers based on triphenylamine (TPA) and tetraphenylethylene (TPE) as building blocks via direct Pd-catalyzed reactions and their application in CO2 capture and explosive detection.

In this study, we report the synthesis of π-conjugated network polymers via palladium-catalyzed direct arylation polycondensation of triphenylamine (TPA) and tetraphenylethylene (TPE) with different active substrates. Moreover, six conjugated porous polymers were obtained (named as TPA-TPA-MA, TPA-PB-MA, TPA-TFB-MA, TPA-TPE-MA, TPE-PB-MA, and TPE-TFB-MA). Then, the fluorescence properties in the solid and dispersed states, the corresponding microporous structures, and the Brunauer–Emmett–Teller (BET) surface areas of all polymers were well studied. Among the obtained materials, TPA-PB-MA possessed not only largest BET surface area (686 m2 g−1) and largest pore volume (0.716 cm3 g−1), but also the smallest pore size of 0.823 nm. These properties are very beneficial for the application of TPA-PB-MA in CO2 storage and PA sensing. At 1 bar, TPA-PB-MA demonstrated the significant CO2 uptake of 2.70 and 1.35 mmol g−1 at 273 and 298 K, respectively. Furthermore, TPA-PB-MA was most sensitive and selective towards PA recognition. The KSV constant was measured as 4.0 × 104 M−1.

Synthesis of paracyclophanes with planar and central chirality: kinetic resolution of [2.2]paracyclophane aldimines via palladium-catalyzed addition of arylboronic acids

Kinetic resolution of [2.2]paracyclophane aldimines was achieved through a palladium-catalyzed enantioselective arylation, providing access to chiral paracyclophanes with planar and central chirality as well as the recovered chiral aldimines.

Synthesis of chiral seven-membered cyclic sulfonamides through palladium-catalyzed arylation of cyclic imines

An enantioselective palladium-catalyzed addition of arylboronic acids to seven-membered cyclic N-sulfonyl aldimines and ketimines has been developed, giving the chiral cyclic sulfonamides with excellent yields and up to 99% ee.

Palladium-catalyzed direct C2-arylation of azoles with aromatic triazenes.

A highly efficient palladium-catalyzed arylation of azoles at the C2-position using 1-aryltriazenes as aryl reagents was developed. Azoles including oxazoles, thiazoles, imidazoles, 1,3,4-oxadiazoles, and oxazolines could react with 1-aryltriazenes smoothly to generate the corresponding products in good to excellent yields, and various substitution patterns were tolerated toward the reaction.

Synthesis of 3-Substituted Pyrrolidines via Palladium-Catalyzed Hydroarylation

SummaryMetal-catalyzed reactions have revolutionized synthetic chemistry, allowing access to unprecedented molecular architectures with powerful properties and activities. Nonetheless, some transformations remain sparse in number, or out of reach, even with the diverse modern catalytic chemical arsenal, including bimolecular alkene hydroarylation reactions. We report here a broad-scope, palladium-catalyzed pyrroline hydroarylation process that gives 3-aryl pyrrolidines, a class of small molecules with potency in a diverse range of biological scenarios. Thus, whereas N-acyl pyrrolines usually undergo palladium-catalyzed arylation to give alkene products, the corresponding reactions of N-alkyl pyrrolines deliver products of hydroarylation, pyrrolidines. The process has broad substrate scope and can be used to directly deliver drug-like molecules in a single step from readily available precursors.

Palladium-Catalyzed Synthesis of 2,3-Diaryl- N-methylindoles from ortho-Alkynylanilines and Aryl Pinacol Boronic Esters.

A palladium-catalyzed synthesis of 2,3-diaryl- N-methylindoles from o-alkynylanilines and aryl pinacol boronic esters was developed. The system possesses high functional group tolerance and a broad substrate scope with a variety of aryl pinacol boronic esters to provide valuable 2,3-diaryl- N-methylindoles in moderate to good yields. Remarkably, the sequential reaction controlled by iridium-catalyzed C-H borylation or palladium-catalyzed alkynylation followed by the present palladium-catalyzed C3 arylation reaction provided functionalized 2,3-diaryl- N-methylindoles in good yields.

Palladium-Catalyzed Selective Five-Fold Cascade Arylation of the 12-Vertex Monocarborane Anion by B-H Activation.

A series of cage penta-arylated carboranes have been synthesized by palladium-catalyzed intermolecular coupling of the C-carboxylic acid of the monocarba- closo-dodecaborate anion [CB11H12]- with iodoarenes by direct cage B-H bond functionalization. These transformations set a record in terms of one-pot directing group-mediated activation of inert bonds in a single molecule. The methodology is characterized by high yields, good functional group tolerance, and complete cage regioselectivity. The directing group COOH can be easily removed during or after the intermolecular coupling reaction. The mechanistic pathways were probed using density functional theory calculations. A Pd(II)-Pd(IV)-Pd(II) catalytic cycle is proposed, in which initial coupling is followed by preferred B-H activation of the adjacent boron vertex, and continuation of this selectivity results in a continuous walking process of the palladium center. The methodology opens a new avenue toward building blocks with 5-fold symmetry.

The First Kilogram Synthesis of Beclabuvir, an HCV NS5B Polymerase Inhibitor

The process development and kilogram-scale synthesis of beclabuvir (BMS-791325, 1) is described. The convergent synthesis features the use of asymmetric catalysis to generate a chiral cyclopropane fragment and coupling with an indole fragment via an alkylation. Subsequent palladium-catalyzed intramolecular direct arylation efficiently builds the central seven-membered ring. The target was prepared in 12 linear steps with five isolations in an overall yield of 8%.

Palladium-Catalyzed Arylation of Aromatic Amides Directed by a [4-Chloro-2-(1H-pyrazol-1-yl)phenyl]amine Auxiliary

A palladium-catalyzed ortho-arylation of aromatic amides ­directed by [4-chloro-2-(1H-pyrazol-1-yl)phenyl]amine as a bidentate auxiliary has been established. The reaction is characterized by normal working conditions, a broad substrate scope, and a wide functional-group tolerance. In particular, the protocol is compatible with highly sterically demanding ortho-substituted anilides and aryl iodide partners, with good yields.

Reactivity of 5-aminopyrazoles bearing a cyclopropyl group at C3-position in palladium-catalyzed direct C4-arylation

Pyrazole derivatives bearing a cyclopropyl group at C3-position and an amino substituent at C5 were successfully employed in palladium-catalyzed direct arylations. These couplings were performed using air-stable PdCl(C3H5)(dppb) catalyst associated to KOAc as inexpensive base, and afforded regioselectively the C4-arylated pyrazoles without decomposition of the cyclopropyl unit and formation of amination products. A wide variety of functional groups on the aryl bromide including electron-withdrawing and electron-donating ones such as nitrile, nitro, propionyl, ester, trifluoromethyl, chloro, fluoro or methoxy was tolerated. Moreover, from 5-aminopyrazoles bearing N-2′-bromoaryl or 2′-bromobenzenesulfonamide substituent on the amino group, intramolecular Pd-catalyzed direct arylations allowed the formation of tricyclic compounds by formation of 5- or 6-membered rings. © 2018 Elsevier Science. All rights reserved.

Decarboxylative arylation of substituted pyrroles N-protected with 2-(trimethylsilyl)ethoxymethyl (SEM)

Palladium-catalyzed decarboxylative arylation is reported using pyrroles N-protected with the 2-(trimethylsilyl)ethoxymethyl (SEM) group and featuring 2-, 3-, and 4-substituents about the pyrrolic framework. In contrast to N-protected pyrroles previously used in decarboxylative arylation, the use of SEM allows deprotection under mild conditions.

Palladium-Catalyzed Enantioselective Arylation of Racemic Ketones to Form Bridged Bicycles via Dynamic Kinetic Resolution.

Enantioselective α-arylation of racemic ketones containing existing α'-stereocenters is reported for the first time via base-induced dynamic kinetic resolution. Bridged bicyclic rings are formed in good ee values, which are difficult to obtain otherwise. Furthermore, reactions in DMSO-d6 resulted in extensive deuteration of both α- and α'-positions in the products, thus supporting a pathway involving rapid, reversible deprotonation of ketones under catalytic conditions.

Palladium-catalyzed desulfitative arylation of sulfonamides with sodium arylsulfinates

ABSTRACTA Pd(II)-catalyzed desulfitative arylation protocol between sulfonamides and sodium arylsulfinates was herein reported. The direct arylation reaction was successfully achieved by a Pd(II)/Ag(I)-mediated system without participation of any external ligands with a release of SO2. And different N-aryl sulfonamides were obtained readily in up to 86% yields, exhibiting good functional groups tolerance (25 examples).

Palladium-Catalyzed Intramolecular Oxidative Arylations for the Synthesis of Fused Biaryl Sulfones.

This study unveils palladium-catalyzed intramolecular oxidative cyclizations in biaryl and heterobiaryl sulfones providing direct access to fused biaryl sulfones (dibenzothiophene-5,5-dioxides). Variously substituted dibenzothiophene-5,5-dioxides could be readily prepared in good to excellent yields under optimized conditions. In addition, bromination afforded dibromo derivative of dibenzothiophene-5,5-dioxides, providing platform for late-stage diversification. The translational applications of this current protocol have successfully been demonstrated in the synthesis of 2,8-diamino derivative of dibenzothiophene-5,5-dioxides, a α7-nicotinic acetylcholine receptor agonist analogue, and novel single fluorene-tethered dibenzothiophene-5,5-dioxide, an organic emitter.

Synthesis of a 1,2-Dithienylethene-Containing Donor-Acceptor Polymer via Palladium-Catalyzed Direct Arylation Polymerization (DArP).

This paper reports the synthesis of D-A polymers containing 1,2-dithienylethene (DTE) units via palladium-catalyzed direct arylation polymerization (DArP). The reaction of dibromoisoindigo (1-Br) and DTE (2-H), in the presence of Pd2(dba)3·CHCl3 (0.5 mol%), P(2-MeOC6H4)3 (L1) (2 mol%), pivalic acid (1 equiv) as catalyst precursors, and Cs2CO3 (3 equiv) as a base affords poly(1-alt-2) with a high molecular weight (Mn up to 44,900). Although, it has been known that monomers, with plural C–H bonds, tend to form insoluble materials via direct arylation at undesirable C–H positions; the reaction of 1-Br and 2-H cleanly proceeds without insolubilization. The resulting polymer has a well-controlled structure and exhibits good charge transfer characteristics in an organic field-effect transistor (OFET), compared to the polymer produced by Migita–Kosugi–Stille cross-coupling polymerization. The DArP product displays an ideal linear relationship in the current–voltage curve, whereas the Migita–Kosugi–Stille product shows a VG-dependent change in the charge mobility.

Highly Selective Pd-Catalyzed Direct C-F Bond Arylation of Polyfluoroarenes.

A directing-group-free palladium-catalyzed direct arylation of simple polyfluoroarenes with arylboronic acids through selective C-F bond activation is described. The combination of Pd(OAc)2 with BrettPhos was identified as an efficient catalytic system to promote the reaction with high regioselectivity and broad substrate scope. Preliminary mechanistic studies reveal that the oxidative addition of Pd to the C-F bond is involved in the catalytic cycle.