Cyclization vs. Elimination Reactions of 5‐Aryl‐5‐hydroxy 1,3‐Diones: One‐Pot Synthesis of 2‐Aryl‐2,3‐dihydro‐4H‐pyran‐4‐ones

2‐Aryl‐2,3‐dihydro‐4H‐pyran‐4‐ones were prepared in one step by cyclocondensation of 1,3‐diketone dianions with aldehydes. The use of HCl (10%) for the aqueous workup proved to be very important to avoid elimination reactions of the 5‐aryl‐5‐hydroxy 1,3‐diones formed as intermediates. The TiCl₄‐mediated cyclization of a 2‐aryl‐2,3‐dihydro‐4H‐pyran‐4‐one with 1,3‐silyloxybuta‐1,3‐diene resulted in cleavage of the pyranone moiety and formation of a highly functionalized benzene derivative.     

A Three‐Component One‐Pot Synthesis of Functionalized 5,5‐Dicyanocyclopenta‐1,3‐dienes from Arylidene­malononitriles,Activated Acetylenes,and KCN or KSCN

The reaction of dialkyl acetylenedicarboxylates with arylidenemalononitriles in the presence of KSCN in MeCN led to a mixture of dialkyl (3E)‐4‐aryl‐3‐(arylideneamino)‐5,5‐dicyanocyclopenta‐1,3‐diene‐1,2‐dicarboxylates and dialkyl 4‐aryl‐5‐cyanothiophene‐2,3‐dicarboxylates. When these reactions were performed in the presence of KCN, only the functionalized 5,5‐dicyanocyclopenta‐1,3‐dienes were obtained.     

Ruthenium Catalyzed C−H Acylmethylation of N‐Arylphthalazine‐1,4‐diones with α‐Carbonyl Sulfoxonium Ylides: Highway to Diversely Functionalized Phthalazino‐fused Cinnolines

A direct ortho‐Csp²‐H acylmethylation of 2‐aryl‐2,3‐dihydrophthalazine‐1,4‐diones with α‐carbonyl sulfoxonium ylides is achieved through a Ru^II‐catalyzed C?H bond activation process. The protocol featured high functional group tolerance on the two substrates, including aryl‐, heteroaryl‐, and alkyl‐substituted α‐carbonyl sulfoxonium ylides. Thereafter, 2‐(ortho‐acylmethylaryl)‐2,3‐dihydrophthalazine‐1,4‐diones were used as potential starting materials for the expeditious synthesis of 6‐arylphthalazino[2,3‐a]cinnoline‐8,13‐diones and 5‐acyl‐5,6‐dihydrophthalazino[2,3‐a]cinnoline‐8,13‐diones under Lawesson's reagent and BF₃?OEt₂ mediated conditions, respectively. Of these, the BF₃?OEt₂‐mediated cyclization proceeded in DMSO as a solvent and a methylene source via dual C?C and C?N bond formations.     

Facile Synthesis and Palladium‐Catalyzed Cross‐Coupling Reactions of 2,3‐Bis(pinacolatoboryl)‐1,3‐butadiene

Treatment of 1,1‐bis(pinacolatoboryl)ethene with an excess of 1‐bromo‐1‐lithioethene gave 2,3‐bis(pinacolatoboryl)‐1,3‐butadiene in high yield. Palladium‐catalyzed cross‐coupling of the resulting diborylbutadiene with aryl iodides took place smoothly in the presence of a catalytic amount of Pd(OAc)₂/PPh₃ and aqueous KOH to give 2,3‐diaryl‐1,3‐butadienes in good yields. The coupling reaction with commercially available 4‐acetoxyphenylmethyl chloride under the same conditions followed by hydrolysis of the acetyl groups gave anolignan B in a one‐pot manner. A variety of [3]‐ to [6]dendralenes were synthesized by palladium‐catalyzed coupling of the diene or 1,1‐bis(pinacolato)borylethene with alkenyl or dienyl halides, respectively, in good yields.     

Facile Synthesis of Spirooxindole‐Cyclohexenes via Phosphine‐Catalyzed [4 + 2] Annulation of α‐Substituted Allenoates

A phosphine‐catalyzed [4 + 2] annulation of α ‐substituted allenoate with exocyclic alkene moiety of oxindoles or indan‐1,3‐diones has been developed. Thus, under the catalysis of PPh₃ (20 mol%), a series of spirooxindole‐ or spiroindan‐1,3‐dione‐cyclohexenes have been obtained in moderate to excellent yields and regioselectivity from the annulations of α ‐methyl allenoates with 3‐methyleneoxindoles or 2‐methyleneindan‐1,3‐diones. This method offers an easy access to structurally novel spirocyclohexenes.     

Asymmetric Synthesis of Axially Chiral 2‐Aminobiaryls by Rhodium‐Catalyzed Benzannulation of 1‐Arylalkynes with 2‐(Cyanomethyl)phenylboronates

Asymmetric benzannulation of 1‐arylalkynes, where the aryl group is an ortho‐substituted aromatic group, with 2‐(cyanomethyl)phenylboronate was catalyzed by a rhodium complex coordinated with a chiral diene ligand to give high yields of axially chiral 2‐aminobiaryls with greater than 90 % ee.     

Rhodium‐Catalyzed Defluorinative Vinylation of gem‐Difluoroalkenes for the Synthesis of 2‐Fluoro‐1,3‐dienes

Herein, we present a strategy for the formation of 2‐fluoro‐1,3‐diene derivatives via rhodium‐catalyzed direct C(sp²)—C(sp²) cross‐coupling of gem‐difluoroalkenes and acrylamides. By merging Rh(III)‐catalyzed C(sp²)–H bond activation and nucleophilic addition/F‐elimination of gem‐difluoroalkene, an efficient defluorinative vinylation reaction is uncovered, which leads to the generation of 2‐fluoro‐1,3‐dienes in moderate to good yields with excellent stereoselectivity under mild conditions. Preliminary mechanistic study suggests unique effects of fluorine substituents which allow the reactivity profile not observed with the congeners bearing heavier halides.     

New Approaches to the Synthesis of 4‐(2‐Aminophenyl)‐1,3‐dihydro‐2H‐imidazol‐2‐ones and 3‐Ureidoindoles and a Study of Their Interconversion

3‐Alkyl/aryl‐3‐ureido‐1H,3H‐quinoline‐2,4‐diones ( 2 ) and 3a‐alkyl/aryl‐9b‐hydroxy‐3,3a,5,9b‐tetrahydro‐1H‐imidazo[4,5‐c]quinoline‐2,4‐diones ( 3 ) react in boiling concentrated HCl to give 5‐alkyl/aryl‐4‐(2‐aminophenyl)‐1,3‐dihydro‐2H‐imidazol‐2‐ones ( 6 ). The same compounds were prepared by the same procedure from 2‐alkyl/aryl‐3‐ureido‐1H‐indoles ( 4 ), which were obtained from the reaction of 3‐alkyl/aryl‐3‐aminoquinoline‐2,4(1H,3H)‐diones ( 1 ) with 1,3‐diphenylurea or by the transformation of 3a‐alkyl/aryl‐9b‐hydroxy‐3,3a,5,9b‐tetrahydro‐1H‐imidazo[4,5‐c]quinoline‐2,4‐diones ( 3 ) and 5‐alkyl/aryl‐4‐(2‐aminophenyl)‐1,3‐dihydro‐2H‐imidazol‐2‐ones ( 6 ) in boiling AcOH. The latter were converted into 1,3‐bis[2‐(2‐oxo‐2,3‐dihydro‐1H‐imidazol‐4‐yl)phenyl]ureas ( 5 ) by treatment with triphosgene. All compounds were characterized by ¹H‐ and ¹³C‐NMR and IR spectroscopy, as well as atmospheric pressure chemical‐ionisation mass spectra.     

Rhodium‐Catalyzed Arylation of Cyclopropenes Based on Asymmetric Direct Functionalization of Three‐Membered Carbocycles

A variety of highly diastereo‐ and enantiomerically enriched arylcyclopropanes is obtained through the asymmetric rhodium‐catalyzed arylation reaction of achiral nonfunctionalized cyclopropene derivatives with commercially available aryl boronic acids in the presence of (R,S)‐Josiphos.     

Pd‐Catalyzed Synthesis of α‐Aryl Vinylphosphonates via Suzuki Arylation of α‐Phosphonovinyl Nonaflates

The first palladium‐catalyzed method for the arylation of α‐phosphonovinyl nonaflates is described. Using a catalyst comprised of Pd(OAc)₂ and SPhos, terminal and internal α‐aryl vinylphosphonates could be efficiently accessed under mild conditions. The reaction features a broad coupling partner scope and tolerates many functional groups.     

Synthesis of Hexahydrospiro[pyrazolo[3,4‐b]quinoline‐4,1′‐pyrrolo[3,2,1‐ij]quinoline‐2′,5(1H,4′H)‐diones] from 5,6‐dihydro‐4H‐pyrrolo[3,2,1‐ij]quinoline‐1,2‐dione Using Fe3O4@Cu(OH)x as a Nanocatalyst

The tricyclic isatin, 5,6‐dihydro‐4H‐pyrrolo[3,2,1‐ij]quinoline‐1,2‐dione, undergoes three‐component, one‐pot reactions with 1‐aryl‐3‐methylpyrazole‐5‐amines and cyclohexane‐1,3‐diones producing hexacyclic spiro products, hexahydrospiro[pyrazolo[3,4‐b]quinoline‐4,1‐pyrrolo[3,2,1‐ij]quinoline‐2′,5(1H,4′H)‐diones]. Comparable spiro condensation products are also obtained using 4‐hydroxy‐2H‐1‐benzopyran‐2‐one in place of cyclohexane‐1,3‐diones.     

Acid Catalyzed Efficient Syntheses of Aryl‐5H‐dibenzo[b,i]xanthene‐5,7,12,14‐(13H)‐tetraones and 3,3‐(Arylmethylene)bis(2‐hydroxynaphthalene‐1,4‐diones) and In Vitro Evaluation of their Antioxidant Activity

A simple and efficient synthesis of aryl‐5H‐dibenzo[b,i]xanthene‐5,7,12,14‐(13H)‐tetraones and 3,3‐(arylmethylene)bis(2‐hydroxynaphthalene‐1,4‐diones) by the condensation of aromatic aldehydes and 2‐hydroxy‐1,4‐naphthoquinone under extremely mild conditions using catalytic amount of H₂SO₄ or in the presence of acidic ionic liquid 1‐butyl‐3‐methylimidazolium hydrogen sulphate, which could be recycled, has been reported. The radical scavenging capacity of the synthesized compounds has been examined towards the stable free radical 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH), and the compounds 2 were found to scavenge DPPH free radical efficiently.     

Enantioselective Conjugate Addition‐Protonation of 5H‐Oxazol‐4‐ones and 5‐Methylene 1,3‐Oxazolidine‐2,4‐diones: 2,2'‐Biphenol‐Induced Diastereoselectivity Switch

A synthetic strategy for catalytic asymmetric conjugate addition‐protonation and diastereoselective switch between 5H‐oxazol‐4‐ones and 5‐methylene 1,3‐oxazolidine‐2,4‐diones was established. An array of chiral conjugate addition‐protonation products bearing 1,3‐O‐heterotertiary‐O‐heteroquarternary nonadjacent stereocenters were obtained in excellent yields, moderate to good diastereoselectivities, and excellent enantioselectivities (up to 97% yield, 11: 1 dr, and 98% ee). Induction by 2,2’‐biphenol could effectively promote the production of the corresponding diastereoisomers via cycloaddition intermedia.     

Original recyclization of S‐phenacyl derivatives of 4‐acylamino‐2‐mercapto‐1,3‐oxazoles and their analogues

Readily accessible acylamino(chloro)acetophenones, if treated with sodium rhodanide and α‐halogenocarbonyl compounds, provide 4‐acylamino‐5‐aryl‐2‐mercapto‐1,3‐oxazole derivatives which undergo recyclization on heating in polyphosphoric acid to give substituted 1,3‐thiazol‐2(3H)‐ones or 1,3‐thiazolidin‐2,4‐diones containing 2‐alkyl(aryl)‐5‐aryl‐1,3‐oxazol‐4‐yl residues at the N³ atom. © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:432–437, 2007; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20317     

Efficient Synthesis of Dialkyl (2Z)‐2‐[(E)‐1‐Aryl‐2‐(3‐arylquinoxalin‐2‐yl)ethenyl]but‐2‐enedioates

The reaction of dialkyl acetylenedicarboxylates 4 with 1‐aryl‐2‐[(3‐arylquinoxalin‐2(1H)‐ylidene)ethanones 3 in the presence of Ph₃P leads to dialkyl (2Z)‐2‐[(E)‐1‐aryl‐2‐(3‐arylquinoxalin‐2‐yl)ethenyl]but‐2‐enedioates 1 in good yields.     

N‐functionalized azolin‐2‐ylidene‐palladium‐catalyzed heck reaction

Novel 1,3‐dialkylimidazolidinium, 1,3‐dialkyl‐3,4,5,6‐tetrahydropyrimidinium, and 1,3‐dialkyl‐1H‐4,5,6,7‐tetrahydrodiazepinium hexafluorophosphates ( 1a–c, 2a–c ) as N‐heterocyclic carbene precursors have been synthesized and characterized. The incorporation of saturated N‐heterocyclic carbenes into palladium precatalysts gives high‐catalyst activity in the Heck coupling of aryl bromide substrates in aqueous media. The complexes were generated in the presence of Pd(OAc)₂ by in situ deprotonation of 1,3‐dialkylazolinium salts 1, 2 . © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:82–86, 2008; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20415     

Synthesis of Enantiomerically Pure 1,2,3,4‐Tetrahydro‐β‐carbolines and N‐Acyl‐1‐aryl Ethylamines by Rhodium‐Catalyzed Hydrogenation

The rhodium‐catalyzed asymmetric hydrogenation of different enamides, in particular, dihydro‐β‐carboline derivates, was investigated in the presence of chiral phosphorus ligands. Enantioselectivities of up to 99 % ee were obtained after ligand screening and optimization of the reaction conditions. The scope and limitation of the catalysts were shown in the synthesis of optically active tetrahydro‐β‐carbolines and other benchmark N‐acyl‐1‐aryl ethylamines.     

Pd‐Catalyzed Carbonylative α‐Arylation of Aryl Bromides: Scope and Mechanistic Studies

Reaction conditions for the three‐component synthesis of aryl 1,3‐diketones are reported applying the palladium‐catalyzed carbonylative α‐arylation of ketones with aryl bromides. The optimal conditions were found by using a catalytic system derived from [Pd(dba)₂] (dba=dibenzylideneacetone) as the palladium source and 1,3‐bis(diphenylphosphino)propane (DPPP) as the bidentate ligand. These transformations were run in the two‐chamber reactor, COware, applying only 1.5 equivalents of carbon monoxide generated from the CO‐releasing compound, 9‐methylfluorene‐9‐carbonyl chloride (COgen). The methodology proved adaptable to a wide variety of aryl and heteroaryl bromides leading to a diverse range of aryl 1,3‐diketones. A mechanistic investigation of this transformation relying on ³¹P and ¹³C NMR spectroscopy was undertaken to determine the possible catalytic pathway. Our results revealed that the combination of [Pd(dba)₂] and DPPP was only reactive towards 4‐bromoanisole in the presence of the sodium enolate of propiophenone suggesting that a [Pd(dppp)(enolate)] anion was initially generated before the oxidative‐addition step. Subsequent CO insertion into an [Pd(Ar)(dppp)(enolate)] species provided the 1,3‐diketone. These results indicate that a catalytic cycle, different from the classical carbonylation mechanism proposed by Heck, is operating. To investigate the effect of the dba ligand, the Pd⁰ precursor, [Pd(η³‐1‐PhC₃H₄)(η⁵‐C₅H₅)], was examined. In the presence of DPPP, and in contrast to [Pd(dba)₂], its oxidative addition with 4‐bromoanisole occurred smoothly providing the [PdBr(Ar)(dppp)] complex. After treatment with CO, the acyl complex [Pd(CO)Br(Ar)(dppp)] was generated, however, its treatment with the sodium enolate led exclusively to the acylated enol in high yield. Nevertheless, the carbonylative α‐arylation of 4‐bromoanisole with either catalytic or stoichiometric [Pd(η³‐1‐PhC₃H₄)(η⁵‐C₅H₅)] over a short reaction time, led to the 1,3‐diketone product. Because none of the acylated enol was detected, this implied that a similar mechanistic pathway is operating as that observed for the same transformation with [Pd(dba)₂] as the Pd source.     

Synthesis of Structurally Diversified Benzo[c]chromene Derivatives under (An)aerobic Conditions Catalyzed by CuI

2‐Bromobenzoic acids underwent an α‐arylation with cyclohexane‐1,3‐diones to give 1H‐benzo[c]chromene‐1,6(2H)‐diones under Ar atmosphere catalyzed by CuI/l ‐proline in the presence of Cs₂CO₃. The subsequent regioselective oxidation took place under O₂ balloon automatically based on the substituents for the construction of structurally diversified benzo[c]coumarin derivatives.     

Synthesis of 3,5‐Diarylcyclohex‐2‐enones by NH4Cl/HCl‐Catalyzed Cyclization and Deacetylation of 4‐Acetylhexane‐1,5‐diones

A new route for the synthesis of 3,5‐diarylcyclohex‐2‐enones is reported. The 4‐acetyl‐1,3‐diarylhexane‐1,5‐diones were obtained by the addition of pentane‐2,4‐dione to chalcones. The reaction of 4‐acetyl‐1,3‐diarylhexane‐1,5‐diones with NH₄Cl/HCl in EtOH under reflux conditions gave the 3,5‐diarylcyclohex‐2‐enones in good yields. All synthesized compounds were characterized by spectroscopic methods (¹H‐, ¹³C‐NMR, and IR), and elemental analyses.