Synthesis of 3-aryl-4-chalcogen-2H-benzopyrans from 3-iodo-4-chalcogen-2H-benzopyrans using a Suzuki cross-coupling

The Suzuki cross-coupling reaction of 3-iodo-4-chalcogen-2H-benzopyran derivatives with a variety of organoboron compounds in the presence of catalytic amount of palladium salt is described. This cross-coupling reaction proceeded cleanly and was performed with aryl boronic acids bearing electron-withdrawing, electron-donating, and neutral substituents, furnishing the corresponding products in moderate to good yields.     

Electrophilic cyclization of 3-alkynyl-4-chalcogen-2-H-chromenes: synthesis of 3-halo-chalcogenophene[3,2-c]chromene derivatives

An efficient synthesis of 3-halo-chalcogenophene[3,2-c]chromene has been accomplished via electrophilic cyclization reaction of 3-alkynyl-4-chalcogen-2H-chromene using I₂, PhSeBr, and BuTeBr₃ as electrophilic sources. The cyclization reaction proceeded cleanly under mild reaction conditions, and 3-halochalcogen-chromenes were formed in good yields. In addition, the obtained 3-iodo-chalcogenophene-chromenes were readily transformed to more complex products using a metal-halogen exchange reaction with n-BuLi and trapping the lithium-intermediate formed with aldehyde, furnishing the desired secondary alcohol in good yield. Conversely, using the palladium catalyzed cross-coupling reactions with terminal alkynes and boronic acid, we were able to obtain the Sonogashira and Suzuki type products in good yields.     

Synthesis of 1H-pyrrolo[3,2-c]quinoline derivatives via palladium-catalyzed heteroannulation of 2-aryl-3-iodo-4-(phenylamino)quinolines and 4-(N,N-allylphenylamino)-2-aryl-3-iodoquinolines

Palladium(0)/copper iodide catalyzed Sonogashira cross-coupling of 2-aryl-3-iodo-4-(phenylamino)quinolines with terminal alkynes afforded series of 1,2,4-trisubstituted 1H-pyrrolo[3,2-c]quinolines in a single-step operation. Conversely, the 4-(N,N-allylphenylamino)-2-aryl-3-iodoquinoline derivatives were found to undergo PdCl₂(PPh₃)₂/CuI catalyzed intramolecular Heck reaction to yield the corresponding 1,3,4-trisubstituted 1H-pyrrolo[3,2-c]quinolines.     

Efficient synthesis of 2-oxazolidinones and quinazoline-2,4(1H,3H)-diones from CO2 catalyzed by tetrabutylammonium fluoride

By employing tetrabutylammonium fluoride (TBAF) as a catalyst, the various carboxylative cyclizations of the propargylic amines having internal alkynes with CO₂ proceeded to afford the corresponding 2-oxazolidinones. In this case, it was also found that the generated 2-oxazolidinones were tautomerized into the corresponding 2-oxazolones due to the basicity of TBAF. In addition, we performed the synthesis of quinazoline-2,4(1H,3H)-dione from 2-aminobenzonitrile and CO₂ by using TBAF as a catalyst.     

A convenient hydroiodination of alkynes using I2/PPh3/H2O and its application to the one-pot synthesis of trisubstituted alkenes via iodoalkenes using Pd-catalyzed cross-coupling reactions

A facile hydroiodination of alkynes using readily-available reagents such as I₂, PPh₃, and H₂O has been developed. This is extended to the one-pot synthesis of trisubstituted alkenes from alkynes via iodoalkenes using Pd-catalyzed cross-coupling and related methods such as the Suzuki–Miyaura cross-coupling, Sonogashira cross-coupling reaction, and Mizoroki–Heck reaction.     

Synthesis of 1H-indol-2-yl-(4-aryl)-quinolin-2(1H)-ones via Pd-catalyzed regioselective cross-coupling reaction and cyclization

An efficient and novel route for the synthesis of 1H-indol-2-yl-(4-aryl)-quinolin-2(1H)-one 1 via palladium-catalyzed site-selective cross-coupling reaction and cyclization process was described. Reaction of 3-bromo-4-trifloxy-quinolin-2(1H)-one 3 with arylboronic acid catalyzed by PdCl₂(PPh₃)₂ afforded 3-bromo-4-aryl-quinolin-2(1H)-one 4, which then reacted with 2-ethynylaniline 5 via Pd-catalyzed Sonogashira coupling and CuI-mediated cyclization leading to the desired 1H-indol-2-yl-(4-aryl)-quinolin-2(1H)-one 1 in good yields.     

Facile synthesis of novel CF3-substituted ring-fused furo[2,3-c]pyrazoles through Rh2(OAc)4 catalyzed [3+2] cycloaddition of 4-diazo-1-phenyl-3-(trifluoromethyl)-1H-pyrazol-5(4H)-one with aromatic alkynes

The Rh₂(OAc)₄ catalyzed [3+2] cycloaddition of 4-diazo-1-phenyl-3-(trifluoromethyl)-1H-pyrazol-5(4H)-one with aromatic alkynes was studied, and this protocol can be efficiently applied to the synthesis of the novel CF₃-substituted ring-fused furo[2,3-c]pyrazoles.     

Palladium-catalyzed Suzuki-Miyaura couplings of potassium aryl trifluoroborates with 4-tosyloxycoumarins or 4-tosyloxyquinolin-2(1H)-one

Pd(PPh₃)₄ catalyzed Suzuki-Miyaura cross-coupling reactions of 4-tosyloxycoumarins or 4-tosyloxyquinolin-2(1H)-one with various potassium aryl trifluoroborates afforded the corresponding 4-substituted coumarins or 4-substituted quinolin-2(1H)-ones in good to excellent yield.     

Acid-promoted cyclization of 2-propynolphenols leading to 4-tosyloxy-2H-chromenes

A novel and efficient p-TsOH-promoted cascade cyclization of 2-propynolphenols is developed to give 4-tosyloxy-2H-chromenes in moderate to efficient yields. It is noted that p-TsOH acts not only as a promoter in this reaction, and also as the sulfonate source. Importantly, the obtained 4-tosyloxy-2H-chromenes can be used as versatile intermediates for the synthesis of various functionalized compounds through diverse metal-catalyzed cross-coupling reactions. Moreover, this method can be enlarged to gram scale.     

Synthesis of 4-(2-hydroxyaryl)-3-nitro-4H-chromenes

A combinatorial library of 4-(2-hydroxyaryl)-3-nitro-4H-chromenes was synthesized in high yield by C4-SMe substitution in N-alkyl/phenyl 4-(methylthio)-3-nitro-4H-chromen-2-amines with a variety of phenols. The reaction always provided C2 substitution in the phenol ring, dictated by hydrogen bond interactions between the phenolic hydroxyl group and the nitro group in 3-nitro-4H-chromenes. Reduction of the nitro group with concomitant hydrolysis of the enamine in 4-(2-hydroxyaryl)-3-nitro-4H-chromenes with Zn, Ac₂O in AcOH furnished hybrid amino-acid lactone incorporating ortho-tyrosine and phenyl alanine moieties.     

Synthesis of isatin-conjugated 3H-indole-N-oxides and their serendipitous conversion to spiroindolenines

Isatin-conjugated 3H-indole-N-oxides were synthesized from isatin-derived propargylic alcohols and nitrosobenzenes in moderate yields. Isatin-conjugated 3H-indole-N-oxides were converted to novel spiroindolenines under PPh₃-mediated deoxygenation reaction condition, serendipitously.     

Synthesis of substituted 4-(1H-indol-6-yl)-1H-indazoles as potential PDK1 inhibitors

The development of a preparative route to a series of novel 4-(1H-indol-6-yl)-1H-indazole compounds as potential PDK1 inhibitors is described. The synthetic strategy centres on the late-stage Suzuki cross-coupling of N-unprotected indazole and indole fragments. The use of a monoligated palladium catalyst system was found to be highly beneficial in the cross-coupling reaction. The indazole and indole fragments were constructed by diazotisation/cyclisation and S_NAr/reductive cyclisation sequences, respectively.     

Synthesis of 5-substituted 2-(4- or 3-methoxyphenyl)-4(1H)-quinolones

5-Substituted 7-methoxy-2-(4- or 3-methoxyphenyl)-4(1H)-quinolones 8-17 have been synthesised in good yields from the corresponding 7-methoxy-2-(4- or 3-methoxyphenyl)-5-trifluoromethanesulfonate-4(1H)-quinolones 7 via palladium-mediated cross-coupling reactions or aromatic nucleophilic substitution (SN_Ar) reactions.     

One-pot synthesis of quinazolin-4(3H)-ones and fused quinazolinones by a palladium-catalyzed domino process

An efficient one-pot synthesis of quinazolin-4(3H)-ones, benzoimidazo[2,1-b]quinazolin-12(6H)-ones and imidazo[2,1-b]quinazolin-5(1H)-ones via a palladium-catalyzed domino process has been developed. The Pd-catalyzed reactions of 2-azidobenzamides 1 with isocyanides 2 produced quinazolin-4(3H)-ones 4 at room temperature by a domino Pd-catalyzed cross-coupling/carbodiimide-mediated cyclization. However, as 2-azido-N-(2-bromophenyl)benzamides 1 were used under heating condition in the presence of Cs₂CO₃, the benzoimidazo[2,1-b]quinazolin-12(6H)-ones 5 were directly obtained by twice Pd-catalyzed domino cyclization. A domino reogioselective 5-exo-dig intramolecular cyclization reaction of alkynyl-containing azides 6 with isocyanides 2 generated imidazo[2,1-b]quinazolin-5(1H)-ones 9 in 74–93% yields in the presence of catalyst Pd(PPh₃)₄ and K₂CO₃.     

Reductive coupling of hydantoins with benzophenones by low-valent titanium: Synthesis of 4-substituted 1H-imidazol-2(3H)-ones and unusual two-to-two coupled products

The reductive coupling of 1,3-dimethyhydantoin with benzophenones by TiCl₄-Zn in THF gave 4-diarylmethyl-1H-imidazol-2(3H)-ones as four-electron reduced one-to-one coupled products and their dimers as two-to-two coupled products predominantly by controlling the reaction conditions. The reductive coupling of 5-alkyl-1,3-dimethyhydantoins with benzophenones produced 5-alkyl-4-diarylmethyl-1H-imidazol-2(3H)-ones as the sole products irrespective to the reaction conditions. On the other hand, the reductive coupling of 1,3-dimethyhydantoin with cyclic benzophenones selectively 4-arylhydroxymethyl-1H-imidazol-2(3H)-ones as two-electron reduced one-to-one coupled products and they were further reduced to 4-diarylmethyl-1H-imidazol-2(3H)-ones.     

ReBr(CO)5-catalyzed sequential addition-cyclization of 1,3-dicarbonyl compounds with electron-deficient internal alkynes affording trisubstituted 2H-pyran-2-ones

The reaction of 1,3-dicarbonyl compounds such as acetoacetate, acetylacetone, dibenzoylmethane, and benzoylacetate with electron-deficient internal alkynes in the presence of catalytic amount of ReBr(CO)₅ in toluene under neutral conditions resulted in the formation of 4,5,6-trisubstituted 2H-pyran-2-ones in moderate to high yield. The reaction took place via a two-step sequence including the rhenium(I)-catalyzed addition of the activated methylenes to alkynes to give enolic 2-alkenyl derivatives, and subsequently dealcoholic cyclization to form 2H-pyran-2-one derivatives.     

Synthesis of novel 2H,5H-dihydrofuran-3-yl ketones via ISNC reactions

Unique 1-[2H,5H-dihydrofur-3-yl]ketones have been synthesized from propargylic nitroethers via intramolecular cycloadditions involving silyl nitronates. Various substituent groups were placed on the 2 and 5 positions of the dihydrofuran rings. We examined the scope of the long-range coupling in proton NMR of the oxo-dihydrofuran products. The identities of the diastereomers resulting from the Michael addition/cycloaddition reactions were tentatively assigned for the first time. CAChe MNDO PM5 and CONFLEX programs were engaged to assist with the identification of these stereoisomers. The reaction times and conditions for these oxo-dihydrofurans were found to be different from that of the published dihydrofuranals, which led us to propose a different mechanism.     

Synthesis of 2-amino-3-cyano-4H-chromen-4-ylphosphonates and 2-amino-4H-chromenes catalyzed by tetramethylguanidine

Synthesis of 2-amino-4H-chromen-4-ylphosphonates and 2-amino-4H-chromenes has been accomplished by the reaction of salicylaldehyde, malononitrile, dialkyl/diphenylphosphites catalyzed by 1,1,3,3-tetramethylguanidine (TMG) under neat conditions at room temperature. The applicability of catalytic TMG for the synthesis of 2-amino-4H-chromenes also has been described. The mild reaction conditions, simple work-up procedure, and use of TMG as an inexpensive catalyst provides an economical protocol for the preparation of important phosphorus-containing compounds.     

Rapid access to 4-substituted-pyrones and 2(5H)-furanones via a palladium-catalyzed C-OH bond activation

An efficient palladium-catalyzed cross-coupling reaction of 4-hydroxy-pyrone or 4-hydroxy-2(5H)-furanone with arylboronic acid is described, which affords the 4-substituted-pyrones and 2(5H)-furanones in good yields. This transformation proceeds through a C-OH bond activation under mild conditions.     

Synthesis of 2-bromo-1-aryl-1H-indenes via a Ag(I) promoted domino 2π-electrocyclic ring-opening/4π-electrocyclization reaction of 1,2-diaryl substituted gem-dibromocyclopropanes

2-Bromo-1-aryl substituted indenes can be synthesized from 1,2-diaryl substituted gem-dibromocyclopropanes via a domino reaction sequence. The cascade reaction involves silver(I) promoted ionization and 2π-disrotatory electrocyclic ring-opening, followed by a 4π-conrotatory electrocyclic ring closing reaction of the allylic carbocation intermediate. Reaction conditions utilize silver tetrafluoroborate (AgBF₄) in dichloroethane at 65 °C. Selectivity effects for the electrocyclization were also studied. The 2-bromoindenes can be further functionalized using cross-coupling reactions, such as the Suzuki–Miyaura protocol. The alkene π-bond of the indenes can also be isomerized to give the thermodynamically more stable 2-bromo-3-aryl-1H-indene isomers using triethylamine in dichloromethane at room temperature.