Isotope-labeling of the fibril binding compound FSB via a Pd-catalyzed double alkoxycarbonylation

We have synthesized two isotopically labeled variants of the β-amyloid binding compound FSB possessing (13)C-labels on the two terminal aryl carboxylic acid moieties. One of these was also fully deuterated on the olefinic spacers. The (13)C-isotope labeling was achieved applying a Pd-catalyzed methoxycarbonylation of the corresponding aryl chlorides with externally (ex situ) generated (13)C-labeled CO. Application of the Shirakawa-Hayashi protocol for the Pd-catalyzed reduction of a dialkyne intermediate using D(2)O allowed for the selective deuterium labeling of the two trans-C,C double bonds of FSB.     

An expedient synthesis of ellipticine via Suzuki-Miyaura coupling

A simple and efficient total synthesis of ellipticine was developed via the Suzuki-Miyaura coupling of sterically sensitive 2-hydroxybenzeneboronic acid with a multifunctional aryl halide using Pd(OAc)₂ as a catalyst and Cu(OAc)₂·H₂O as an additive in DMSO/H₂O as a key step followed by double N-arylation and cyclization.     

An expedient synthesis of β-aralkyl cycloalkanones via the sequential conjugate addition of allyl arylacetates and Pd-catalyzed decarboxylative protonation protocol

An expedient protocol for the synthesis of β-aralkyl cycloalkanones was developed via the conjugate addition of allyl arylacetate to cycloalkenones and the following Pd-catalyzed decarboxylative protonation strategy.     

An expedient synthesis of 2,4,5-trisubstituted 1,4-pentadienes from Baylis-Hillman adducts via the Pd-catalyzed decarboxylation-elimination protocol

We disclosed an efficient synthetic method of 2,4,5-trisubstituted 1,4-pentadienes from Baylis-Hillman adducts via the Pd-catalyzed decarboxylation-elimination protocol as the key step.     

An expedient aralkylation of Baylis-Hillman adduct via the Pd-catalyzed decarboxylative protonation strategy

An expedient protocol of aralkylation of Baylis-Hillman adducts has been developed. This method used Pd-catalyzed decarboxylative protonation strategy to the allyl ester precursor that was made from the Baylis-Hillman adduct and allyl phenylacetate.     

Pd-catalyzed sequential reactions via allene intermediate for the synthesis of polycyclic frameworks containing 2,3-dihydrofuran units

A stepwise process involving Sonogashira coupling, propargyl allenyl isomerization, and consecutive [4 + 2] cyclization has been realized, leading to an efficient synthesis of polycyclic compounds containing a 2,3-dihydrofuran unit. Most attractive for synthetic interest is the finding that up to four stereogenic centers could be generated in one step with high stereoselectivity.     

Chemoselective three-component coupling via a tandem Pd-catalyzed boron-Heck and Suzuki reactions

A new approach is herein reported to prepare biaryl derivatives via a tandem Pd-catalyzed boron-Heck and Suzuki reactions. This one-pot tandem process avoided purification or addition of extra catalyst between steps. The resulting biaryl compounds can be prepared with substrate variability in good to moderate yields.     

Efficient synthesis of fluorinated biphenyl derivatives via Pd-catalyzed Suzuki coupling reactions in aqueous solvents at room temperature

A variety of fluorinated biphenyl derivatives were obtained in good yields in aqueous solvents at room temperature by Suzuki coupling reaction of aryl bromides and aryl boronic acid in the presence of high activity catalyst—some air-stable hemilabile PO coordinated cyclopalladated complexes. The structures of above catalysts were characterized by element analyses, IR, ¹H NMR, ¹³C NMR and ³¹P NMR.     

An expedient one-pot sequential five-component synthesis of highly substituted spiro-pyrrolidine heterocycles

An expedient one-pot sequential five-component synthesis of highly substituted pyrrolidine heterocycles involving [3+2]-cycloaddition of azomethine ylides as the key step is described. The protocol provides a mild reaction condition, high yield of the products, high regioselectivity and operational simplicity to assemble complex structural entity in a single operation. The structure of the product was confirmed by spectroscopic and single crystal X-ray analysis.     

A one-pot,two-step synthesis of 3-deazacanthin-4-ones via sequential Pd-catalyzed Suzuki-Miyaura and Cu-catalyzed Buchwald-Hartwig reactions

3-Deazacanthin-4-one and nine analogues, including the 8-aza analogue, were prepared rapidly and in high yields from 8-iodoquinolones and 2-chloro(het)arylboronic acids. The strategy involves construction of the central B ring via concomitant Pd-catalyzed Suzuki-Miyaura CC and Cu-catalyzed Buchwald-Hartwig CN coupling reactions.     

Mild conditions for the synthesis of functionalized pyrrolidines via Pd-catalyzed carboamination reactions

[reaction: see text] The palladium-catalyzed carboamination of N-protected gamma-aminoalkenes with aryl bromides and triflates has been achieved under new, mild reaction conditions using the weak base Cs(2)CO(3) in dioxane solvent. These reactions tolerate a wide variety of functional groups, including enolizable ketones, nitro groups, methyl esters, and acetates, which are not compatible with previously described conditions.     

Biaryl synthesis via Pd-catalyzed decarboxylative coupling of aromatic carboxylates with aryl halides

A new strategy for the regiospecific construction of unsymmetrical biaryls is presented, in which easily available salts of carboxylic acids are decarboxylated in situ to give arylmetal species that serve as the nucleophilic component in a catalytic cross-coupling reaction with aryl halides. The catalyst system consists of a copper phenanthroline complex that mediates the extrusion of CO2 from aromatic carboxylates to generate arylcopper species, and a palladium complex that catalyzes the cross-coupling of these intermediates with aryl halides. This bimetallic system allows the direct coupling of various aryl, heteroaryl, or vinyl carboxylic acids with aryl or heteroaryl iodides, bromides, or chlorides at 160 degrees C in the presence of a mild base such as potassium carbonate. The present scope and potential economic impact of the reaction are demonstrated by the synthesis of 42 biaryls, some of which are of substantial industrial relevance. Remaining challenges and future perspectives of the new transformation are discussed.     

Biaryl synthesis via decarboxylative Pd-catalyzed reactions of arenecarboxylic acids and diaryliodonium triflates

A novel simple and efficient synthesis of biaryls via a Pd-catalyzed decarboxylative cross-coupling reaction of arenecarboxylic acids and diaryliodonium triflates is described. The PdCl2/DPEphos catalytic system in the presence of Ag2CO3 in DMSO was found to be the most efficient. Various biaryls, including sterically hindered biaryls, were synthesized with yields ranging from 37 to 85%.     

Versatile and facile synthesis of diverse semisynthetic tetracycline derivatives via Pd-catalyzed reactions

A diverse collection of tetracycline derivatives has been synthesized utilizing Heck, Suzuki, and other palladium-coupling reactions via tetracycline arenediazonium and iodoarene salts. Large numbers of tetracyclines are now possible via these reactions, including numerous upper periphery derivatives of doxycycline, minocycline, sancycline, and methacycline modified at positions C7, C9, and C6-C13 on the tetracycline naphthacene ring. Application of palladium-coupling reactions to the tetracyclines has yielded new tetracycline classes with differing structural attributes, greatly increasing the structural diversity of this family of antibiotics, one of the last of the early antibiotic families to be expanded by organic and medicinal chemistry.     

Enantioselective synthesis of 1-vinyltetrahydroisoquinolines via Pd-catalyzed intramolecular asymmetric allylic amination reactions

1-Vinyltetrahydroisoquinolines serve as versatile intermediates for the synthesis of a variety of naturally occurring isoquinoline alkaloids. 1-Vinyl-6,8-dimethoxytetrahydroisoquinoline 4 and 1-vinyl-5,6,7-trimethoxytetrahydroisoquinoline 6 with >90% ee by means of Pd-catalyzed intramolecular asymmetric allylic amination reactions, using MPN and BOP ligands, developed in our laboratory. The fine-tuning capability of the MPN and BOP ligands has played a significant role in the optimization of enantioselectivity. Interesting substituent effect as well as solvent effect on the product selectivity and enantioselectivity was observed. Plausible mechanisms are proposed, which can accommodate various findings, including the critical importance of the activation of the trifluoroamide moiety through its coordination to the Lewis acidic Pd²⁺ metal center.     

Stereocontrolled synthesis of bicyclic ureas and sulfamides via Pd-catalyzed alkene carboamination reactions

The synthesis of bicyclic ureas and sulfamides via palladium-catalyzed alkene carboamination reactions between aryl/alkenyl halides/triflates and alkenes bearing pendant cyclic sulfamides and ureas is described. The substrates for these reactions are generated in 3–5 steps from commercially available materials, and products are obtained in good yield with up to >20:1 diastereoselectivity. The stereochemical outcome of the sulfamide alkene addition is consistent with a mechanism involving anti-aminopalladation of the alkene, whereas the stereochemical outcome of the urea alkene addition is consistent with a syn-aminopalladation mechanism.     

An expedient synthesis of salviadione

An expedient synthesis of the alkaloid salviadione, the only to date isolated naturally occurring 1H-benzo[def]carbazole is described. The key step in the synthesis is a palladium-catalyzed, carbon monoxide-mediated reductive N-heterocyclization of a nitroarene with an adjacent alkene.     

Pd-catalyzed efficient one-pot sequential cross-coupling reactions of aryl dihalides

The palladium complex containing N-heterocyclic carbene ligands catalyzes one-pot sequential Heck/Suzuki, Heck/Heck, and Heck/Sonogashira coupling reactions of aryl dihalides to afford unsymmetrically substituted arenes in excellent yields.     

An expedient synthesis of homophthalimides

The six-membered heterocyclic subunit of homophthalimides can be obtained by a direct, hitherto unprecedented, radical cyclisation onto an aromatic ring starting from a xanthate precursor.     

A general solid phase synthesis of 4-substituted quinolinones via Pd-catalyzed cross coupling

A general method for the solid phase synthesis of 4-hydroxy quinolinones and subsequent Pd-catalyzed cross coupling to afford 4-substituted quinolinones has been developed. Conversion of support-bound 4-hydroxy quinolinones to 4-tosyl quinolinones and subsequent treatment with alkyl, aryl, benzylzinc halides, or arylboronic acids in the presence of catalytic amount of Pd(PPh₃)₄ provides 4-alkyl, aryl, or benzyl quinolinones. This method allows for the introduction of alkyl, aryl, and benzyl groups at the 4-position of the quinolinone ring, and is ideal for parallel and combinatorial chemistry library synthesis.