Palladium-catalyzed intramolecular vinylarylation of alkene: Access to spirocyclic scaffold

A Pd(0)-catalyzed cascade reaction of (Z)-1-iodo-1,6-diene bearing a N-heteroaryl ring, including indole, pyrrole as well as imidazole, is reported. The reaction proceeds via Heck-type carbopalladation, which is followed by C-H activation of the attached N-hetero ring, thus delivering 6,5-spirocycles in moderate to good yields. Furthermore, the preliminary attempt at asymmetric version was also conducted.     

Palladium-catalyzed multi-acetoxylation of 1,3-disubstituted 1H-pyrazole-5-carboxylates via direct C(sp2)-H or C(sp3)-H bond activation

A palladium-catalyzed multi-acetoxylation of 1,3-disubstituted 1H-pyrazole-5-carboxylate derivatives containing multiple potential reactive sites is described. Therein, the sequence of this process has been appropriately investigated. The protocol mainly provides the di- and tri-acetoxylated products for 1,3-diarylpyrazoles. Besides, it is found that the acetoxylation of C(sp³)-H bond is prior to that of C(sp²)-H bond under structurally competitive conditions.     

Palladium-catalyzed ortho-selective C–H bond chlorination of aromatic ketones

A palladium-catalyzed ortho-selective C–H bond chlorination reaction for the preparation of 2-chloro aromatic ketones was described. Both electron-withdrawing and electron-donating groups on the aromatic rings are well tolerated under the optimized conditions. The 2-chloro aromatic ketones obtained by our method could be applied to synthesize the derivatives of 1H-indazole or benzo[d]isoxazole.     

Palladium-catalyzed direct heteroarylation of chloropyridines and chloroquinolines

The direct coupling of aryl chlorides with heteroarenes would be a considerable advantage for sustainable development due to their lower cost, lower mass, the wider diversity of available compounds and also because of the formation of only HCl associated to a base as by-product and the reduction of the number of steps to prepare these compounds. We observed that through the use of PdCl(dppb)(C₃H₅) as a catalyst, a range of heteroaryl derivatives undergoes coupling via C-H bond activation/functionalization reaction with chloropyridines or chloroquinolines in low to high yields. This air-stable catalyst can be used with a wide variety of substrates. The position of the chloro substituent on pyridines has a minor influence on the yields. On the other hand, the nature on the heteroaryl derivative has a large influence. The highest yields were obtained using benzoxazole, thiophene or thiazole derivatives. The coupling of chloropyridines with furans also gave the expected products, but in low to moderate yields.     

Palladium-catalyzed synthesis of indole fused coumarins via cross-dehydrogenative coupling

The present method describes a palladium-catalyzed cross-dehydrogenative coupling reaction of coumarin and aniline for the synthesis of indole fused coumarin derivatives. The one-pot method is operationally simple and molecular oxygen is used as sole oxidant. The target compounds are obtained in good yields from commercially available precursors.     

Palladium(II)-catalyzed arylation of unactivated C(sp3)-H bonds by using 2,1,3-benzoselenadiazole-4-amine as directing ligand

A modified bidentate directing ligand derived from 2,1,3-benzoselenadiazole (BSeD) was designed and synthesized. It exhibited high regioselectivity in the catalytic activation of unactivated C(sp³)-H bonds with aryl iodides in the presence of palladium catalyst in yields up to 94%.     

Palladium-catalyzed direct 5-arylation of formyl- or acetyl-halothiophene derivatives

Pd(OAc)₂ was found to catalyze the direct arylation of some functionalized halothiophene derivatives allowing the synthesis in only one step of polyfunctionalized arylated thiophenes. In the presence of 2-acetyl-3-chlorothiophene, 2-acetyl-4-chlorothiophene, 2-acetyl-3-bromothiophene diethylacetal or 2-(4-bromothiophen-2-yl)-[1,3]dioxolane, and a variety of aryl bromides, the 5-arylation products were obtained in moderate to high yields employing only 0.5 mol% catalyst. On the other hand, the use of 2-formyl-3-chlorothiophene, 2-acetyl-3-bromothiophene or 2-formyl-3-bromothiophene gave disappointing results.     

Palladium-catalyzed alkenation of thiophenes and furans by regioselective C-H bond functionalization

A palladium-catalyzed direct alkenation of thiophenes and furans has been developed in the presence of AgOAc and pyridine. A variety of olefinic substrates such as acrylates, acrylamides, and acrylonitrile can perform the direct oxidative coupling reactions with various thiophenes and furans to give the mono-alkenylated products in good yields. In most cases, the (E)-isomers were isolated as the major products.     

Palladium-catalyzed functionalization of indoles with 2-acetoxymethyl substituted electron-deficient alkenes

A new functionalization of indoles via palladium-catalyzed reaction of indoles and 2-acetoxymethyl substituted electron-deficient alkenes is reported. The reaction was carried out under neutral condition and no isomerization of the carbon-carbon double bond was observed.     

Palladium-catalyzed oxime ether directed regioselective C-H alkoxylation of arenes

A palladium-catalyzed highly regioselective ortho-C(sp²)-H alkoxylation of oxime ethers with PhI(OAc)₂ as the oxidant and alcohols as the alkoxylation reagents has been developed. Mono-alkoxylated and acetoxylated products could be selectively obtained via tuning the reaction conditions. A series of oxime ethers were tolerated, affording the corresponding products in moderate to good yields. Both primary and secondary alcohols survived the reaction conditions. Moreover, the directing group can be easily removed, thereby providing a straightforward access to substituted aryl ketones.     

Palladium-catalyzed coupling reaction of amino acids (esters) with aryl bromides and chlorides

The bulky and electron-rich MOP type ligands and Pd(dba)₂ combinations showed high efficiency for the coupling reactions of amino acids and inactive aryl halides to give N-aryl amino acids. Under the catalytic conditions, not only α-amino acids, but also β-, γ-, and δ-amino acids have been coupled with aryl chlorides in moderate to high yields; in the case of optically pure β-amino acids as substrates, the optical purities of the coupling products retained.     

Direct ortho-arylation of 2-arylbenzoxazoles via C-H activation

A new and highly regioselective arylation of 2-arylbenzoxazoles based on C-H activation has been developed. The results represent the first examples of palladium-catalyzed direct ortho-arylation of 2-arylbenzoxazoles and also provide a facile route for the synthesis of complicated structures containing arylated benzoxazoles moieties.     

Modified palladium-catalyzed regioselective ortho-arylation of sp C-H bond substrates with a low catalyst loading

A novel and generally applicable system for ortho-arylation of a broad range of sp² C-H bond substrates such as arylated benzoxazoles, acylated anilines, and pyridines has been developed. The arylation was performed in trifluoroacetic acid (TFA) under air by using PdCl₂ as the catalyst with a low catalyst loading of 1 mol %. And it was found for the first time that the addition of weak base K₃PO₄ to the acidic solvent could remarkably enhance the reaction rate. The arylated products were isolated in moderate to good yields with high regioselectivity for the substrates containing a meta-substituent. This arylation is tolerant with various functional groups such as CH₃, CH₃O, CH₃CO, Br, and Cl.     

Application of a catalytic palladium biaryl synthesis reaction, via C-H functionalization, to the total synthesis of Amaryllidaceae alkaloids

The total synthesis of the Amaryllidaceae alkaloids dehydroanhydrolycorine, hippadine, pratosine, anhydrolycorine, assoanine, anhydrolycorin-7-one and oxoassoanine was achieved from the appropriate N-benzylisatin precursors using an intramolecular, palladium catalyzed, dehydrohalogenation, biaryl synthesis reaction to establish the carbon skeleton of the natural products. In order to avoid the formation of regioisomers in the cyclization reactions it was found necessary to incorporate the halogen on the benzyl group. Borane reduction of the 7H-pyrrolo[3,2,1-de]phenanthridine-4,5-dione derivatives gave 7H-pyrrolo[3,2,1-de]- and 4,5-dihydro-7H-pyrrolo[3,2,1-de]-phenanthridines (dehydroanhydrolycorine, dehydroassoanine, anhydrolycorine and assoanine). The former were readily reduced to the latter with NaCNBH₃ to give anhydrolycorine and assoanine. These compounds were then oxidized to anhydrolycorin-7-one and oxoassoanine whilst the same mixtures of borane reduction products could be oxidized to give hippadine and pratosine.     

C-H activations on a 1H-1,4-benzodiazepin-2(3H)-one template

Air stable benzodiazepine containing palladacycles were synthesized by a C-H activation reaction and studied by mass spectrometry and X-ray crystallography. Catalytic C-H functionalizations of 1-methyl-5-phenyl-1H-1,4-benzodiazepin-2(3H)-one with diphenyliodonium hexafluorophosphate led to a mixture, which included the starting material and the expected product 1-methyl-5-(2′-biphenyl)-1H-1,4-benzodiazepin-2(3H)-one.     

Palladium-catalyzed asymmetric tandem allylic substitution using chiral 2-(phosphinophenyl)pyridine ligand

Palladium-catalyzed asymmetric tandem allylic substitution of (Z)-1,4-diacyloxy- and (Z)-1,4-bis(alkoxycarbonyloxy)-2-butene (2a-c) using 2-(phosphinophenyl)pyridine 1 as chiral ligand provided optically active six-membered 2-vinyl-1,4-diheterocyclic compounds with good to high enantioselectivity. For example, the reactions with catechol, 2-(benzylamino)phenol, or 1,2-bis(benzylamino)ethane as a nucleophile gave 2-vinyl-1,4-benzodioxane (71% ee), 4-benzyl-2-vinyl-1,4-benzoxazine (86% ee), and 1,4-dibenzyl-2-vinylpiperazine (86% ee), respectively.     

Amide-directed arylation of sp C-H bonds using Pd(II) and Pd(0) catalysts

Protocols to effect β-arylation of sp³ C-H bonds via Pd(II)/(IV) and Pd(0)/(II) catalytic cycles have been achieved using a newly developed monodentate CONHC₆F₅ directing group. These reactions provide an unprecedented means to functionalize sp³ C-H bonds in aliphatic carboxylic acid-derived substrates.     

Regioselective iridium(I)-catalysed remote borylation of oxygenated naphthalenes

We present our investigations into the regioselective borylation and halogenation of polyoxygenated naphthalene systems that are key precursors to dimeric pyranonaphthoquinone natural products. A variety of oxygenated naphthalenes were successfully borylated with pinacolborane in high yield and excellent regioselectivity using [Ir(COD)OMe]₂ and di-tert-butylbipyridine (dtbpy). The boronates were also readily transformed into the corresponding halides, opening new avenues for the preparation of advanced Suzuki coupling substrates useful for the synthesis of natural products.     

Synthesis, characterization and solid state structures of thiosemicarbazone palladacycles: Influence of hydrogen bonding in the molecular arrangement

Treatment of the thiosemicarbazones 4-FC₆H₄C(Me)NN(H)C(S)NHR, (R = Me, a; Ph, b) and 2-ClC₆H₄C(Me)NN(H)C(S)NHR (R = Ph, c) with lithium tetrachloropalladate(II) in methanol or palladium(II) acetate in acetic acid gave the tetranuclear cyclometallated complex [Pd{4-FC₆H₃C(Me)NNC(S)NHR}]₄ (1a, 1b) and [Pd{2-ClC₆H₃C(Me)NNC(S)NHPh}]₄ (1c). Reaction of these tetramers with the diphosphines dppe, t-dppe, dppp or dppb in a 1:2 molar ratio gave the dinuclear cyclometallated complexes [(Pd{4-FC₆H₃C(Me)NNC(S)NHR})₂(μ-Ph₂P(CH₂)_nPPh₂)], (n = 2, 2a, 2b; 3, 4a, 4b; 4, 5a, 5b), [(Pd{4-FC₆H₃C(Me)NNC(S)NHPh})₂(μ-Ph₂PCHCHPPh₂)], (3a, 3b) and [(Pd{2-ClC₆H₃C(Me)NNC(S)NHR})₂(μ-Ph₂P(CH₂)_nPPh₂)], (n = 2, 2c, 2d; 3, 4c, 4d; 4, 5c, 5d), [(Pd{2-ClC₆H₃C(Me)NNC(S)NHPh})₂(μ-PPh₂CHCHPPh₂)], (3c, 3d). The X-ray crystal structure of the ligand b and the complexes 3c, 4a and 4d were determined. The structures of complexes 4a and 4d show that the different disposition of the chain cyclometallated of the thiosemicarbazones (in the same orientation or in the opposite one) is due to the different H bonds produced.     

Study of the solid-state hydrogen isotope exchange ofl-alanine

The solid-state reaction of isotope exchange ofl-alanine (l-Ala) with spillover-hydrogen activated on a Rh(Pd)-supported catalyst was studied. The reactivity of the carbon atoms and the activation energies of isotope exchange of the hydrogen at the C(2) and C(3) atoms of thel-Ala molecule were determined using tritium NMR. Theab initio calculations of the activation energy of a model reaction between the alanine molecule and a hydroxonium cation were carried out. The mechanism and plausible structures of the transition states of this reaction were proposed. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 757–762, April. 1997.