Highly regioselective thiocarbonylation of conjugated dienes via palladium-catalyzed three-component coupling reactions

Three-component coupling reaction of conjugated dienes, thiols, and carbon monoxide affords an atom-economical thiocarbonylation of the dienes to give beta,gamma-unsaturated thioesters as the sole products. A catalyst system based on [Pd(OAc)(2)] and Ph(3)P showed excellent catalytic activity. The thiocarbonylation was performed under an atmosphere of carbon monoxide (400 psi) at 110 degrees C in CH(2)Cl(2) for 60 h. A wide variety of thioesters were synthesized in good to excellent yields from easily accessible starting materials. The reaction is believed to proceed via a eta(3)-allylpalladium intermediate. The thiocarbonylation, which is applicable to a wide variety of conjugated dienes, occurs in high regioselectivity, the latter dependent on the steric characteristics and stability of the eta(3)-allylpalladium complex.     

Synthesis of homoallylic amines via the palladium-catalyzed decarboxylative coupling of amino acid derivatives

Protected homoallylic amines are synthesized by the decarboxylative coupling of alpha-amino acid derivatives. The catalytic C-C bond-forming reaction relies on the bioinspired decarboxylative metalation of alpha-amino acids to produce alpha-amino anion equivalents. The alpha-amino anion equivalents are intercepted by pi-allyl palladium electrophiles to produce substituted homoallylic amines.     

Synthesis of novel electron-deficient chromone-fused dienes via phosphine catalyzed [4+2] annulation

α-Chromonyl ketoesters undergo phosphine catalyzed [4+2]-annulation reactions with acetylene carboxylates to yield tricyclic benzopyrones in good yields. Under mild acidic conditions, the tricyclic benzopyrones rearrange to provide highly substituted and electron-poor chromone-fused dienes in good yields.     

Synthesis of highly substituted pyrrolidines via palladium-catalyzed cyclization of 5-vinyloxazolidinones and activated alkenes

N-Tosyl-5,5-divinyloxazolidin-2-one undergoes a palladium-catalyzed decarboxylative cyclization across a range of electrophilic alkenes to give the corresponding pyrrolidine derivatives bearing two contiguous quaternary centres. Alkenes bearing two electron-withdrawing groups are required; pyrrolidines were not formed from mono-activated alkenes. Bulky, electron-rich phosphines promote pyrrolidine formation with less highly electrophilic, doubly activated alkenes, and a dramatic improvement is observed in the presence of iodide.     

Regioselective synthesis of trifluoromethyl group substituted allylic amines via palladium-catalyzed allylic amination

The palladium-catalyzed regioselective allylic amination of α-trifluoromethylated allyl acetate occurred using Pd(OAc)₂/DPPE and [Pd(π-allyl)(cod)]BF₄/DPPF. The selective formation of the γ-product was attained by Pd(OAc)₂/DPPE, while the α-product was obtained using [Pd(π-allyl)(cod)]BF₄/DPPF.     

Synthesis of thiophene derivatives via palladium-catalyzed coupling reactions

Thiophene derivatives with multiple substitutions are prepared from vinylidene bromide, which is synthesized by the reaction of thiophene-2-carboxaldehyde with carbon tetrabromide in the presence of PPh₃, as a core molecule through several coupling reactions such as Suzuki-Miyaura coupling and palladium-catalyzed CH arylation. The reactions with a wide variety of organic halides lead to a series of substituted thiophene derivatives in moderate to good yields.     

Synthesis of heterocyclic allenes via palladium-catalyzed hydride-transfer reaction of propargylic amines

[reaction: see text] Propargylic diisopropylamines containing heterocycles, which were prepared readily from heterocyclic bromides and propargyldiisopropylamine by the Sonogashira coupling reaction, underwent the allene transformation reaction in the presence of Pd(2)(dba)(3).CHCl(3) catalyst (2.5 mol %) and 1,2-bis[bis(pentafluorophenyl)phosphino]ethane (10 mol %) at 100 degrees C in CHCl(3), giving the corresponding heterocyclic allenes in good to high yields via the palladium-catalyzed hydride-transfer reaction.     

Synthesis of highly substituted cyclohexenes via mixed Lewis acid-catalyzed Diels-Alder reactions of highly substituted dienes and dienophiles

[reaction: see text] A high-yielding method is described for the rapid synthesis of very hindered cyclohexenes by the Diels-Alder reaction of hindered silyloxy dienes and dienophiles using the mixed Lewis acid catalyst system (AlBr(3)/AlMe(3)). Thus, reaction of the hindered diene 4 with various substituted enones gave good yields of the expected cycloadducts even though both partners are quite sterically hindered.     

Synthesis of homoallylic alcohols via palladium-catalyzed coupling of organomercurials and vinylic oxetanes

The reaction of aryl- and vinylmercurials, cupric chloride, 5% aqueous NH₄Cl, oxygen, catalytic amounts of Li2pPdCl4 and vinylic oxetanes affords an excellent route to functionally-substituted homoallylic alcohols.     

Synthesis of (purin-6-yl)methylphosphonate bases and nucleosides

Three approaches to the synthesis of the title (purin-6-yl)methylphosphonates were investigated and compared. While, the Arbuzov reaction of 6-(iodomethyl)purines with triethyl phosphite did not work, Michaelis-Becker alkylation of the sodium salt of diethyl phosphonate with 6-(mesyloxymethyl)purines gave the desired products in good yields. The best method was based on Rh- or Pd-catalyzed cross-coupling reactions of 6-iodopurines with (diisopropoxyphosphorylmethyl)zinc bromide. In this way a small series of 6-(diisopropoxyphosphorylmethyl)purine bases and nucleosides was prepared in high yields.     

Synthesis of allyl cyanamides and N-cyanoindoles via the palladium-catalyzed three-component coupling reaction

The palladium-catalyzed three-component coupling reaction (TCCR) of aryl isocyanides, allyl methyl carbonate, and trimethylsilyl azide was conducted in the presence of Pd(2)(dba)(3).CHCl(3) (2.5 mol %) and dppe (1,2-bis(diphenylphosphino)ethane) (10 mol %). Allyl aryl cyanamides with a wide variety of functional groups were obtained in excellent yields. This palladium-catalyzed TCCR was further utilized for the synthesis of N-cyanoindoles. The reaction of 2-alkynylisocyanobenzenes, allyl methyl carbonate, and trimethylsilyl azide in the presence of Pd(2)(dba)(3).CHCl(3) (2.5 mol %) and tri(2-furyl)phosphine (10 mol %) at higher temperatures afforded N-cyanoindoles in good to allowable yields. (eta(3)-Allyl)(eta(3)-cyanamido)palladium complex, an analogue of the bis-pi-allylpalladium complex, is a key intermediate in the TCCR, and a pi-allylpalladium mimic of the Curtius rearrangement is involved to generate the (eta(3)-allyl)(eta(3)-cyanamido)palladium intermediate.     

Synthesis of diaryl disulfides via the reductive coupling of arylsulfonyl chlorides

A facile synthesis of diaryl disulfides from arylsulfonyl chlorides in the presence of triphenylphosphine has been developed.     

Synthesis of ene-allenes via palladium-catalyzed hydride-transfer reaction of propargylic amines under mild conditions

The palladium-catalyzed allene transformation reaction from propargylic amines proceeded in the presence of Pd₂(dba)₃·CHCl₃ (5 mol %) and (C₆F₅)₂PC₂H₄P(C₆F₅)₂ (10 mol %) in CHCl₃ at room temperature to give the corresponding allenes in good to high yields. Dicyclohexyl groups substituted on the nitrogen of propargylic amines were found to be effective for the current transformation and the conjugated ene-allenes 4 were synthesized from the corresponding propargylic amines 3 under mild conditions.     

Synthesis of N-methyl-d-ribopyranuronamide nucleosides

The synthesis of N-methyl-d-ribopyranuronamide nucleosides is described. The key route is the rearrangement of a 1,2-O-isopropylidene protected furanose sugar with a carboxamide function in the 4-position to a ribopyranuronamide ring. The Lewis acid catalyzed condensation of adenine and thymine nucleobases with the per-O-acetylated N-methyl-d-ribopyranuronamide sugar is used to give the target nucleosides as a mixture of the α and β anomers. The mixture was separated and the final compounds were obtained by deacetylation in basic conditions.     

Synthesis of a dicyclobutylideneethane derivative via sequential palladium-catalyzed Miyaura borylation and Suzuki coupling

An efficient synthesis of a dicyclobutylideneethane derivative was achieved using a palladium-catalyzed reaction of a substituted (bromomethylene)cyclobutane with bis(pinacolato)diboron. The reaction mechanism was investigated in detail. The Suzuki cross-coupling reaction of a (bromomethylene)cyclobutane with arylboronic acid was also achieved.     

Synthesis of naturally occurring pyridine alkaloids via palladium-catalyzed coupling/migration chemistry

The palladium-catalyzed cross-coupling of 3-iodopyridine, long-chain terminal dienes, and benzylic amines or tosylamides provides a novel route to key intermediates for the synthesis of the naturally occurring, biologically active pyridine alkaloids theonelladins C and D, niphatesine C, and xestamine D. This process involves (1) oxidative addition of the heterocyclic iodide to Pd(0), (2) carbopalladation of the least hindered carbon-carbon double bond of the diene, (3) palladium migration, and (4) pi-allylpalladium displacement by the nitrogen nucleophile with simultaneous regeneration of the Pd catalyst. Subsequent hydrogenation and deprotection affords good yields of the natural products. The Pd-catalyzed coupling of 3-iodopyridine and 2-methyl-11-dodecen-1-ol provides a convenient synthesis of a long-chain aldehyde by an analogous palladium migration process, which is easily converted to the pyridine alkaloid ikimine A.     

Synthesis of substituted tetralones as intermediates of CNS agents via palladium-catalyzed cross-coupling reactions

A series of substituted tetralones as intermediates of CNS agents has been synthesized via Pd-catalyzed coupling reactions of 3-(methoxycarbonyl)-1,2,3,4-tetrahydro-1-oxonaphthalen-6-yl trifluoromethanesulfonate (5) with a variety of organometallic reagents.     

Synthesis of modified triazole nucleosides possessing one or two base moieties via a click chemistry approach

Copper-catalyzed 1,3-dipolar cycloaddition of propargyl and azidoethyl thymine and adenine derivatives afforded triazole nucleosides bearing one or two base moieties. A catalytic role of the adenine nucleus was observed and is explained through copper-adenine coordination in the intermediate copper acetylide-azide complex. The antioxidant activity of the obtained cycloadducts was tested.