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A transition metal and base-free synthesis of 3,3-diaryl-2-oxindoles has been developed from 2,2,N-triarylacetamides in the presence of montmorillonite K-10 in 1,2-dichlorobenzene under O2 balloon atmosphere.

Thermal cyclization of E,E,E-trienes prepared from isatines and Morita—Baylis—Hillman bromides results in highly diastereoselective 6π-electrocyclization to form spirocyclic oxindole derivatives (II) and (V).

Various pyrazolo[1,5-a]quinolines were synthesized via the intramolecular Friedel-Crafts reaction of 1-aryl-5-styrylpyrazoles and the following base-catalyzed aerobic oxidation process. The required 1-aryl-5-styrylpyrazoles were readily prepared from the corresponding conjugated dienones and arylhydrazines in a one-pot process.

The title reaction follows an oxidative Heck arylation, allylic palladium migration, aryl C—H bond functionalization/arylation sequence.

E-mail: kimjn@chonnam.ac.krReceived July 1, 2014, Accepted July 21, 2014Intramolecular Diels-Alder (IMDA) reaction of vinylarenes bearing a Z-alkenyl tether, prepared from Morita-Baylis-Hillman (MBH) adducts, afforded arene-fused isoindoline derivatives in good yields. Vinylfurans,vinylthiophenes, and vinylnaphthalenes could be used successfully as dienes, while vinylbenzene failed underthe same reaction conditions.Key Words : Intramolecular Diels-Alder reaction, Morita-Baylis-Hillman adducts, Vinylarenes, IsoindolinesIntroductionThe construction of a cyclohexene ring by using vinyl-arene (such as styrenyl) as a 1,3-diene moiety in both inter-and intramolecular Diels-Alder reactions has been welldocumented.

In addition to 3-azabicyclo[3.1.1]heptanes, bicyclo[3.1.1]heptane, 3-oxabicyclo[3.1.1]heptane and 3-azabicyclo[3.2.0]heptane derivatives could also be prepared.

An efficient synthesis of 1H-benzo[g]indazoles starting from Morita–Baylis–Hillman (MBH) adducts is disclosed. The synthesis was carried out from MBH bromide via a sequential copper-catalyzed alkynylation, one-pot synthesis of pyrazole, propargyl–allenyl isomerization, and a 6π-electrocyclization involving two aromatic π-bonds and an allenyl π-bond.

An expedient oxidative phosphorylation of pyrroles has been disclosed. The reaction of dialkyl phosphite and pyrrole in the presence of AgNO 3 /K 2 S 2 O 8 in DMF/H 2 O (8:1) produced pyrrole-2-phosphonates in good yields. In the absence of dialkyl phosphite, γ-hydroxy-γ-butyrolactam derivative was formed as a major product.

Immune Modulator Research Center, KRIBB, Daejeon 305-806, KoreaReceived July 3, 2013, Accepted August 30, 2013The reaction of 1,3,5-triketones and arylhydrazines provided indolylpyrazole derivatives in a one-pot reactionin good to moderate yields. Both the pyrazole and indole rings were constructed simultaneously withphenylhydrazine, RCOCH

E-mail: kimjn@chonnam.ac.krReceived June 27, 2013, Accepted July 22, 2013Various phenol derivatives were synthesized in a one-pot reaction from MBH acetates and sodium diethyloxalacetate via a [4C+2C] cyclization protocol. In addition, some pyridine derivatives could also besynthesized using the same starting materials, by isolating the S

A facile synthesis of benzofulvenes was carried out starting from the Morita–Baylis–Hillman adducts of 2-bromobenzaldehyde. The synthesis was carried out via the sequential bromination, Wittig reaction with aldehyde, and Pd-catalyzed intramolecular Mizoroki–Heck reaction. The stereochemistry of benzofulvenes was dependent on the reaction condition, especially on the kinds of base and reaction time, and the substituent of starting materials.

Palladium-catalyzed arylation of methyl 2-(acetoxymethyl)acrylate with aryl iodides afforded the primary acetates of Morita–Baylis–Hillman adducts in good yields with high stereoselectivity under mild conditions (50 °C).

A palladium-catalyzed chelation-controlled oxidative arylation of α-methylene-γ-butyrolactones with arenes provided 3-arylmethylbutenolides as major products along with a low yield of α-arylidene-γ-butyrolactones. The selectivity might be due to a chelation between the palladium center and a directing group at the γ-position of α-methylene-γ-butyrolactones.

A transition metal and base-free synthesis of 3,3-diaryl-2-oxindoles has been developed from 2,2,N-triarylacetamides in the presence of montmorillonite K-10 in 1,2-dichlorobenzene under O2 balloon atmosphere.

Palladium-catalyzed arylation of α,β-unsaturated Weinreb amides has been examined to obtain β-aryl-α,β-unsaturated Weinreb amides. The chelation between the palladium center of an alkylpalladium intermediate and Weinreb amide moiety facilitated both coordination and insertion steps.

A palladium-catalyzed oxidative arylation of chromones was examined. A regioselective 2-arylation of chromone was carried out via a double C–H activation process. The procedure provided an expedient approach for the preparation of flavone derivatives.

A palladium-catalyzed oxidative homo-coupling of 1,3-dimethyluracil was examined. Two types of uracil dimer, C5–C5′ linked dimer and C5–C6′ linked dimer were obtained in variable yields depending on the conditions along with a low yield of C5–C5′ and C6–C5′ linked uracil trimer.

Palladium-catalyzed intramolecular arylation at the C-6 position of uracil moiety was examined. Morita–Baylis–Hillman adducts bearing an uracil moiety at the primary position served an efficient way to a benzo[c]pyrimido[1,6-a]azepine scaffold.

An expedient synthetic procedure of γ-alkylidenebutenolides was developed via a sequential indium-mediated Barbier-type reaction of Morita–Baylis–Hillman bromide with aldehyde, lactonization, and double-bond isomerization. Various γ-alkylidenebutenolides including bovolide and its derivatives were synthesized in good overall yields.

Alkenylbutenolides were synthesized regioselectively in good to moderate yields from Baylis–Hillman adducts via a consecutive indium-mediated Barbier type reaction between Baylis–Hillman bromide and aldehyde, PCC oxidation of the homoallylic alcohol, double bond isomerization, and zinc-mediated Barbier type alkenylation protocol.

A practical and efficient synthesis of various 1,2,5-tricarbonyl compounds is described. The synthesis has been carried out by a conjugate addition of methyl cyanoacetate to the β-position of α,β-unsaturated carbonyl compounds and a subsequent copper(I) iodide-catalyzed aerobic oxidation. In addition, various α-aryl- and α-alkyl-α-keto esters have been synthesized using a similar approach.

An efficient method of palladium-catalyzed direct 5-arylation of 1,3-dimethyluracil was developed with a various range of aryl bromides including electron-deficient aryl bromides. 5-Aryluracil derivatives were obtained in moderate to good yields regioselectively most likely via an electrophilic metalation–deprotonation process.

Various indane and cyclobuta[a]indene derivatives were synthesized by palladium-catalyzed cyclization of homoallylic alcohol derivatives prepared from Baylis–Hillman adducts. Especially, cyclobuta[a]indene derivative was synthesized stereoselectively by palladium-catalyzed 5-exo-trig/4-exo-trig cascade cyclization, albeit in moderate yield. The Z isomer was formed exclusively in the presence of Et3N by usual Heck-type carbopalladation process while E isomer with Cs2CO3 most likely by a concerted metalation/deprotonation (CMD) process.

E-mail: kimjn@chonnam.ac.krReceived January 8, 2011, Accepted January 18, 2011Key Words : Baylis-Hillman reaction, α,β-Unsaturated aldehydes, Proton donor, PhenolThe Baylis-Hillman reaction is an efficient carbon-carbonbond-forming reaction between aldehyde and α,β-unsatu-rated carbonyl compound catalyzed by a tertiary amine suchas DABCO.

In this respect, aryl methallyl ethers and N-methallylanilineswere the major subject for the Pd-catalyzed domino reac-tions. The fate of reactive alkylpalladium(II) intermediateformed by the initial Heck-type cyclization is divided largelyinto two categories: (i) termination by anion capture processby sodium formate

An efficient synthesis of trans -α-methylene-γ-butyrolactones is disclosed from syn -homoallylic alcohols via the intramolecular mesylate displacement reaction promoted by nearby ester group under the influence of MsCl/Et 3 N. syn -Homoallylic alcohols were prepared via the In-mediated Barbier reaction of the bromides of Baylis–Hillman adducts.

The reaction of allylindium reagents and N-(cyanoalkyl)amides afforded fully-substituted 4-alkenylimidazoles in moderate yields via the In-mediated Barbier-type allylation of nitrile and the following dehydrative cyclization cascade.

Modified Baylis–Hillman adducts having 2-bromophenyl acetonitrile moiety at the primary position underwent a Pd-catalyzed cascade reaction to provide poly-substituted naphthalene derivatives in reasonable yields. The reaction involved a sequential 5-exo-carbopalladation, C(sp3)–H activation to cyclopropane, ring-opening and concomitant aromatization processes.

in a reasonable yield (69%). However, thewas quite dependent on the reaction time. Depending on time progress formations of other compounds were observed on TLC. Thus the reaction mixture has to be quenched instanta-neously after 4 - 5 min by pouring into cold water, and the crude product has to be separated with organic solvent. Otherwise the yield of product was dramatically decreased. By using this method we carried out the reductions of

We developed an efficient synthetic strategy of poly-substituted 1-arylisoquinolines via an indium-mediated Barbier type allylation from δ-ketonitriles. Initial attack of allylindium species occurred at the nitrile group selectively to form the enamine intermediate, which reacted with the ketone group intramolecularly to furnish the isoquinolines.

We developed an efficient three-step synthetic protocol of γ-hydroxybutenolides starting from the Baylis-Hillman adducts: (i) bromination, (ii) Barbier reaction and (iii) one-pot K 2 CO 3 -mediated synthesis of γ-hydroxybutenolides. In addition, we showed the synthetic applicability of butenolides including self-dimerization, conjugate addition reaction, and alkylations.

The first successful intermolecular Heck reaction between Baylis–Hillman adducts and aryl iodides was achieved under the conditions comprising Pd(OAc) 2 / n -Bu 4 NBr/KOAc in CH 3 CN.

An efficient synthetic method of poly-substituted pyridines was developed. Various poly-substituted pyridines were prepared from the combination of Baylis–Hillman adducts (3 carbons), activated methylene compounds (2 carbons) and ammonium acetate (1 nitrogen) via [3+2+1] annulation protocol in good yields, regioselectively.

Thermal cyclization of E,E,E-trienes prepared from isatines and Morita—Baylis—Hillman bromides results in highly diastereoselective 6π-electrocyclization to form spirocyclic oxindole derivatives (II) and (V).

Various pyrazolo[1,5-a]quinolines were synthesized via the intramolecular Friedel-Crafts reaction of 1-aryl-5-styrylpyrazoles and the following base-catalyzed aerobic oxidation process. The required 1-aryl-5-styrylpyrazoles were readily prepared from the corresponding conjugated dienones and arylhydrazines in a one-pot process.

The title reaction follows an oxidative Heck arylation, allylic palladium migration, aryl C—H bond functionalization/arylation sequence.

In addition to 3-azabicyclo[3.1.1]heptanes, bicyclo[3.1.1]heptane, 3-oxabicyclo[3.1.1]heptane and 3-azabicyclo[3.2.0]heptane derivatives could also be prepared.

E-mail: kimjn@chonnam.ac.krReceived July 1, 2014, Accepted July 21, 2014Intramolecular Diels-Alder (IMDA) reaction of vinylarenes bearing a Z-alkenyl tether, prepared from Morita-Baylis-Hillman (MBH) adducts, afforded arene-fused isoindoline derivatives in good yields. Vinylfurans,vinylthiophenes, and vinylnaphthalenes could be used successfully as dienes, while vinylbenzene failed underthe same reaction conditions.Key Words : Intramolecular Diels-Alder reaction, Morita-Baylis-Hillman adducts, Vinylarenes, IsoindolinesIntroductionThe construction of a cyclohexene ring by using vinyl-arene (such as styrenyl) as a 1,3-diene moiety in both inter-and intramolecular Diels-Alder reactions has been welldocumented.

An efficient synthesis of 1H-benzo[g]indazoles starting from Morita–Baylis–Hillman (MBH) adducts is disclosed. The synthesis was carried out from MBH bromide via a sequential copper-catalyzed alkynylation, one-pot synthesis of pyrazole, propargyl–allenyl isomerization, and a 6π-electrocyclization involving two aromatic π-bonds and an allenyl π-bond.

An expedient synthetic procedure of biaryl derivatives was developed using a palladium-catalyzed, benzoin-mediated redox process from aryl halides. Various biaryls were synthesized in good yields in short time.

Immune Modulator Research Center, KRIBB, Daejeon 305-806, KoreaReceived July 3, 2013, Accepted August 30, 2013The reaction of 1,3,5-triketones and arylhydrazines provided indolylpyrazole derivatives in a one-pot reactionin good to moderate yields. Both the pyrazole and indole rings were constructed simultaneously withphenylhydrazine, RCOCH

E-mail: kimjn@chonnam.ac.krReceived June 27, 2013, Accepted July 22, 2013Various phenol derivatives were synthesized in a one-pot reaction from MBH acetates and sodium diethyloxalacetate via a [4C+2C] cyclization protocol. In addition, some pyridine derivatives could also besynthesized using the same starting materials, by isolating the S

Various 3,3-diallyl isoindolones were synthesized via a indium-mediated Barbier type double allylation reaction of ortho -cyanobenzoates in good yields in short time. The reactivity of nitrile group toward allylindium is sufficient to form a cyclic compound when a suitable electrophilic center is present in the same molecule to trap the imine intermediate.

We developed an efficient synthetic method of diallylated δ-valerolactam and γ-butyrolactam derivatives via an indium-mediated successive double Barbier type allylations starting from the Baylis–Hillman adducts.

Introduction of nucleophiles at the primary position of Baylis-Hillman adducts has been carried out by the nucleophilic substitution reaction from the acetate or primary bromide derivative of Baylis-Hillman adduct. Palladiumassisted introduction of nucleophiles has also been reported in the Baylis-Hillman chemistry via the corresponding πallylpalladium intermediate. Thus we reasoned that one-pot synthesis of dihydronaphthalene could be carried out by Pd-mediated successive allylation and arylation protocol from the reaction of 1a, the acetate of Baylis-Hillman adduct of 2-bromobenzaldehyde, and dimethyl malonate (2a) as in Scheme 1. The reaction between 1a and 2a produced naphthalene derivative 5a (73%) in a one-pot, under the influence of Pd(OAc)2/TBAB/ K2CO3 in DMF at 90 C (3 h), instead of the expected dihydronaphthalene 4a. The reaction mechanism for the one-pot formation of 5a can be postulated as the following successive processes: (i) allylation of 2a via the π-allylpalladium intermediate (I) to produce the substitution product 3a, (ii) Pd-mediated arylation of 3a to dihydronaphthalene 4a via the intermediate (II), and (iii) dealkoxycarbonylation and concomitant aerobic oxidation process to give the final product 5a. In order to clarify the last step of the concomitant dealkoxycarbonylation and aerobic oxidation, we examined the reaction in more detail as in Scheme 2. The reaction of compound 3a, prepared by nucleophilic substitution reaction from 1a and 2a (K2CO3, CH3CN, rt, 3 h, 78%), 1,7,9

presumably due to the increased steric hindrance aroundthe benzoyl moiety. In summary we disclosed an efficient synthetic procedurefor poly-substituted phenol derivatives starting from theBaylis-Hillman adducts. The reaction afforded phenolderivatives regioselectively in moderate to good yields in aone-pot from the readily available starting materials.