Palladium-catalyzed Intramolecular Cyclization Research Articles

Dicyclohepta[cd,ij]-s-indacene-Based Nonbenzenoid Polycyclic Hydrocarbons: Synthesis and Optoelectronic Properties.

Two nonbenzenoid polycyclic hydrocarbons (PHs) bearing one or two dicyclohepta[cd,ij]-s-indacene (DCHI) units were successfully synthesized via palladium-catalyzed intramolecular cyclization. In contrast to the well-known indeno[1,2-b]fluorene skeleton, the as-formed DCHI substructures not only lead to their highly contorted conformations but also significantly contribute to their modulated aromatic structures and optoelectronic properties, such as decreased energy gaps, red-shifted light absorption, and multi-reversible oxidation activity, thus revealing the importance of such nonbenzenoid π extension.

Palladium-catalyzed intramolecular Heck-type carbonylative cyclization cascade reaction and its application in total synthesis of complex natural products

Palladium-catalyzed intramolecular Heck-type carbonylative cyclization cascade reaction and its application in total synthesis of complex natural products

Palladium-catalyzed cyclization borylmethylation: Access to boryl-functionalized benzene-fused heterocycle compounds

A palladium-catalyzed intramolecular cyclization borylmethylation of alkene-tethered aryl iodide with 1,1-diborylmethane has been described. This method offers an efficient route to synthesize various benzo-heterocyclic compounds containing oxygen or nitrogen atoms. Further experiments have demonstrated that the products can be employed to synthesize a series of potentially biological active heterocyclic compounds.

Synthesis of Spiro Polycyclic N-Heterocycles and Indolecarbazoles via Merging Oxidative Coupling and Cascade Palladium-Catalyzed Intramolecular Oxidative Cyclization.

We report a step-economic strategy for the direct synthesis of spiro polycyclic N-heterocycles and indolecarbazole-fused naphthoquinones by merging oxidative coupling and cascade palladium-catalyzed intramolecular oxidative cyclization. In the protocol, bi-indolylnaphthoquinones were first synthesized by oxidative coupling of indoles and naphthoquinones. Subsequent cascade palladium-catalyzed intramolecular oxidative cyclization of bi-indolylnaphthoquinones gave spiro polycyclic N-heterocycles and indolecarbazoles. The intramolecular oxidative cyclization approach could also be realized by the presence or absence of iron catalysts under standard conditions. This protocol is featured with moderate to excellent yields, a wide substrate scope, and divergent structures of products.

Palladium-catalyzed cyclization/carbonylation of iodoarene-tethered propargyl ethers with nitroarenes for the synthesis of acetamides-functionalized benzofurans

A general and efficient protocol based on palladium-catalyzed intramolecular cyclization and reductive aminocarbonylation reaction for the synthesis of acetamide-functionalized benzofurans has been explored. The reaction using iodoarene-tethered propargyl ethers and nitroarenes as the starting materials. This reaction features the formation of structure defined benzofurans with acetamides as attractive functional groups in a single step operation. By using Mo(CO)6 as both CO source and reductant, a variety of acetamides-functionalized benzofurans were obtained in moderate to good yields with good functional group compatibility.

S-Shaped Fused Azacorannulene Dimer: Structural and Redox Properties

S-Shaped Fused Azacorannulene Dimer: Structural and Redox Properties

Bioinspired Palladium-Catalyzed Intramolecular C(sp3 )-H Activation for the Collective Synthesis of Proline Natural Products.

Bioinspired palladium-catalyzed intramolecular cyclization of amino acid derivatives containing a vinyl iodide moiety by C-H activation enabled rapid access to a wide range of functionalized proline derivatives with an exocyclic olefin. To demonstrate the practicality of this methodology, the functionalized prolines were used as intermediates for the synthesis of several natural products: lucentamycin A, oxotomaymycin, oxoprothracarcin, and barmumycin.

Synthesis of 3-substituted 2-oxindoles from secondary α-bromo-propionanilides via palladium-catalyzed intramolecular cyclization.

In contrast to aromatic halides, coupling reactions involving oxidative addition of alkyl halides, especially secondary or tertiary halides, to transition metals tend to be more challenging. Herein a palladium-catalyzed intramolecular cyclization of α-bromo-propionanilides has been developed, delivering a series of 3-substituted 2-oxindoles in high yields. The method features easy to prepare starting materials, broad substrate scope and excellent functional group tolerance. A detailed mechanistic investigation has been performed.

Role of the base Cs2CO3 on the palladium-catalyzed intramolecular cyclization of two bromoindole derivatives to yield paullone-type products.

Reactions for the palladium-catalyzed intramolecular cyclization of the o-bromoindole and the o-bromo-N-methyl-indole derivatives in the presence and absence of base (Cs2CO3) were explored through DFT calculations. For the base-free reactions, the palladium atom firstly interacts with the aromatic rings of the indole molecule to yield a stable adduct. Once this adduct has been formed, reaction proceeds readily to the oxidative addition intermediate that arises from the insertion of the metal atom into the C-Br bond of the organic fragment. Further steps leading to the paullone (or dimethyl paullone) product, mainly those involving the metalation and deprotonation of the inserted intermediate, are not energetically viable for these reactions. When the effect of the base on the metalation-deprotonation steps is modeled by replacing the bromide ion with CO32- in the metal-inserted structure, a feasible pathway connecting the oxidative addition intermediate with the paullone-type product was located for each of the investigated reactions. The results emerging from this study suggest that palladium can insert into the C-Br bond of the indole derivatives to yield the oxidative addition intermediate (without participation of the base). However, the metalation and deprotonation steps that evolve to the paullone-type product take place via a concerted action involving both the metal and the base. Metalation and deprotonation steps that evolve to the paullone-type product take place via a concerted action involving both the metal and the base.

Palladium-Catalyzed Stereoselective Aza-Wacker-Heck Cyclization: One-Pot Stepwise Strategy toward Tetracyclic Fused Heterocycles.

Palladium-catalyzed intramolecular tandem cyclization reactions were conducted for the synthesis of densely cis/cis-fused aza-tetracyclic structures. The process involved a palladium(II)-catalyzed aerobic aza-Wacker reaction, followed by a palladium(0)-catalyzed Heck reaction. The effects of the solvent and benzene substitution pattern on the one-pot, two-step cascade reaction were studied systematically, and a probable mechanism was proposed. Strained pentahydrobenzo[f]cyclopenta[hi]indolizin-6-one and racemic γ-lycorane can also be synthesized rapidly using this palladium-catalyzed aza-Wacker-Heck cyclization reaction.

Synthesis of π-Extended Imidazoles by 1,3-Dipolar Cycloaddition of Polycyclic Aromatic Azomethine Ylides with Nitriles.

Here we report the 1,3-dipolar cycloaddition of polycyclic aromatic azomethine ylides with nitriles to produce highly fused imidazole derivatives, that is, tribenzo[b,g,ij]imidazo[2,1,5-de]quinolizine. The advantages of this transformation are the broad substrate scope and the good functional group compatibility. The subsequent palladium-catalyzed intramolecular cyclization provides an efficient approach to further π-extended imidazoles, that is, 14b1,15-diazadibenzo[fg,ij]cyclopenta[rst]pentaphene.

Access to N-unprotected 2-amide-substituted indoles from Ugi adducts via palladium-catalyzed intramolecular cyclization of o-iodoanilines bearing furan rings

A variety of N-unprotected 2-amide-substituted indoles were synthesized from readily available furfural-based Ugi adducts in moderate to good yields via palladium-catalyzed intramolecular cyclization of o-iodoanilines bearing furan rings. These reactions involved a cascade sequence consisting of dearomatizing arylation, opening of the furan ring, and deprotection of the N atom.

Pd(0)-Catalyzed Intramolecular “Ylide-Ullmann-Type” Cyclization of Carbonyl-Stabilized Phosphonium Ylides and Access to Phosphachromones by Exocyclic P–C Cleavage

An unprecedented palladium-catalyzed intramolecular Ullmann-type cyclization of carbonyl-stabilized phosphonium ylides with aryl bromides was successfully developed. Furthermore, a base-promoted chemoselective hydrolysis of exocyclic P-C bond of the corresponding phosphonium salts delivered various phosphachromones. Excellent selectivity and high efficiency and good functional group tolerance were observed.

Synthesis and Properties of Tri-tert-butylated Trioxa and Trithia Analogues of Truxene

Abstract Trioxa- and trithia-truxene derivatives, 3,8,13- (para) and 2,7,12- (meta) tri-tert-butylated benzo[1,2-b:3,4-b′:5,6-b′′]-trifuran and -tris[1]benzothiophenes (p-tBuTxO, m-tBuTxO, p-tBuTxS, and m-tBuTxS), have been prepared by palladium-catalyzed intramolecular triple dehydrogenative cyclization. While these compounds are soluble in common organic solvents, they have high melting points, mostly more than 300 °C. m-tBuTxO shows a substantial solid state UV fluorescence with a higher quantum efficiency than p-tBuTxO. Both p-tBuTxS and m-tBuTxS, however, exhibit only weak fluorescence in both solution and solid state (the λmax of emission in solid state specifically depends on the substitution pattern), but obvious blue phosphorescence is observed in PMMA film under vacuum at r.t. as well as in MeCy at 77 K, which is attributable to the heavy atom effect of sulfur. Meanwhile, p-tBuTxS exhibits a higher hole mobility compared with that of m-tBuTxS in the evaluation of thin-film FET characteristics. These results are discussed in terms of intrinsic molecular structures and arrangements determined by X-ray crystallography.

Synthesis of carbazoloquinone derivatives and their antileukemic activity via modulating cellular reactive oxygen species.

Carbazoloquinone alkaloids are of great interest as privileged structures for anticancer drug molecules. The purpose of this study was to investigate the structure-activity relationships of carbazoloquinone derivatives as anticancer agents. A series of carbazoloquinones including murrayaquinone A, koeniginequinones A and B, and related analogues were therefore prepared. Palladium-catalyzed intramolecular cyclization reaction mechanism was well elucidated by DFT calculations. Treatment of the synthesized derivatives showed cytotoxicity on human leukemia HL-60 cells in a dose-dependent fashion. In addition, murrayaquinone A and β-brazanquinone elevated cellular levels of reactive oxygen species (ROS), thereby triggering apoptosis. Our findings emphasize the excellent potential of carbazoloquinone derivatives as ROS-inducing anticancer agents.

Complementary regioselective synthesis of 3,5-disubstituted isoxazoles from ynones

Two regioselective synthetic routes towards 3,5-disubstituted isoxazoles from ynones are reported. One route takes place via first converting the ynones to ynone O-methyl oximes, followed by a palladium-catalyzed intramolecular cyclization. The other involves the formation of 5-hydroxy-4,5-dihydroisoxazoles by a cyclocondensation between ynones and hydroxylamine, and subsequent acid mediated dehydration. The two routes are not only both highly regioselective, but also complementary to each other as a pair of regioisomeric 3,5-disubstituted isoxazoles are readily prepared from one single ynone substrate. The efficiency of the two routes are further evaluated and demonstrated in the synthesis of three representative 3,5-disubstituted isoxazoles.

Palladium-catalyzed stereoselective intramolecular cyclization and Suzuki coupling of N-arylsulfonyl-α-chloroenamides promoted by a γ-hydroxy group

The Suzuki reaction of both (E)- and (Z)-α-chloro-γ-hydroxyenamides with benzeneboronic acid by using Pd2(dba)3, tBu3P, and Cs2CO3 proceeded stereoselectively to afford only (E)-trisubstituted enamides. Also, palladium-catalyzed intramolecular cyclization of (E)- and (Z)-α-chloro-γ-hydroxyenamides bearing an N-arylsulfonyl group took place stereoselectively to give the corresponding (E)-2,3-dihydrobenzoisothiazole 1,1-dioxides. The γ-hyroxy group in α-chloroenamides was found to accelerate the present palladium-catalyzed carbon-carbon bond forming reactions.

Synthesis of 3,4-dihydroisoquinoline N-oxides via palladium-catalyzed intramolecular cyclization of 2-alkylbenzaldoximes

Synthesis of 3,4-dihydroisoquinoline N-oxides via palladium-catalyzed intramolecular cyclization of 2-alkylbenzaldoximes

Diphenylphosphine-Oxide-Fused and Diphenylphosphine-Fused Porphyrins: Synthesis, Tunable Electronic Properties, and Formation of Cofacial Dimers.

Diphenylphosphine-oxide-fused NiII porphyrin 8 was synthesized from 3,5,7-trichloroporphyrin 5 via a reaction sequence of nucleophilic aromatic substitution with lithium diphenylphosphide, oxidation with H2 O2 , and palladium-catalyzed intramolecular cyclization. Reduction of 8 with HSiCl3 gave diphenylphosphine-fused NiII porphyrin 9. The embedded P=O and P moieties serve as a strong electron-accepting and electron-donating group to perturb the optical and electrochemical properties of the NiII porphyrin. NiII porphyrin 9 is diamagnetic with a low-spin NiII center in solution but becomes paramagnetic with a five-coordinated NiII center with high-spin (S=1) state in the solid state. Diphenylphosphine-oxide-fused ZnII porphyrin 10 was also synthesized and shown to form a face-to-face dimer with mutual O-Zn bonds in the crystal and in nonpolar and moderately polar solvents. The dimerization of 10 in CDCl3 has been revealed to be an entropy-driven process with a large entropy gain (ΔSD =207 J K-1 mol-1 ).

Enantioselective Construction of Chiral 2,3-cis-Dimethyldihydrobenzofuran with an All-Carbon Quaternary Center: An Efficient Approach to (+)/(−)-PI-220 and (+)-3-epi-Furaquinocin C

A new strategy for the enantioselective construction of chiral 2,3-cis-dimethyldihydrobenzofurans has been developed by a ruthenium-catalyzed asymmetric hydrogenation of racemic α-aryloxybutanone via dynamic kinetic resolution (DKR), combined with a palladium-catalyzed intramolecular reductive Heck cyclization. Starting from optically active 2,3-cis-dimethyldihydrobenzofuran, the natural products (+)/(−)-PI-220 and (+)-3-epi-furaquinocin C were synthesized in high yields.