Nickel‐Catalyzed Formation of a Carbon–Nitrogen Bond at the β Position of Saturated Ketones

Gone fishing : When propiophenone and related ethyl ketones are treated with morpholine in the presence of K₃PO₄, chlorobenzene, and [Ni(cod)₂]/PMe₃ catalyst, a carbon–nitrogen bond is formed selectively at the β position (see scheme; cod=cycloocta‐1,5‐diene). Secondary amines were employed as substrates to give the corresponding β‐enaminones.

     

Modified coumarins. 30. Synthesis of 6-heteroarylcoumarins

Heteroarylcoumarins containing 2-indole, 3-pyrazole, and 4-pyrimidine substituents in the 6-position of the coumarin ring were synthesized. Translated from Khimiya Prirodnykh Soedinenii, No. 2, pp. 145-148, March-April, 2009.     

A simple approach to the synthesis of highly functionalized pyrrole derivatives

The reaction of dibenzoylacetylene and enaminocarbonyl compounds leads to 3-alkylidene-2,3-dihydro-1H-pyrrol-2-ol derivatives in nearly quantitative yields. The reaction of this heterocyclic system with alcohols in the presence of a catalytic amount of HCl produces highly functionalized pyrroles in good yields.     

X-ray crystal structures of new chiral enaminones from 2,4-pentanedione and their heterocyclic derivatives

New chiral enaminones from 2,4-pentanedione (1, 4) and their 1,4-oxazepinium and 1,4-thiazepinium derivatives (5–7) were synthesized and their crystal structures were determined by single crystal X-ray diffraction studies. The crystallographic data for these compounds are as follows: (R)-(1-Methyl-3-oxo-but-1-enylamino)-phenylacetic acid methyl ester (1): a = 7.574(1) ?, b = 12.530(1) ?, c = 14.245(1) ?, P2₁2₁2₁. (R)-4-(2-hydroxy-1-phenyl-ethylamino)-pent-3-en-2-one (2): a = 5.543(1) ?, b = 9.433(1) ?, c = 12.237(2) ?, β = 100.687(3)°, P2₁. (2S, 3R)-3-hydroxy-2-(1-methyl-3-oxobut-1-enylamine) butyric acid methyl ester (3): a = 5.583(1) ?, b = 8.660(1) ?, c = 12.149(1) ?, α = 92.85(1)°, β = 91.00(1)°, γ = 90.16(1)°, P1. (R)-3-[2-Methoxycarbonyl-2-(1-methyl-3-oxo-butylideneamino)-ethyldisulfanyl]-2-(1-methyl-3-oxo-butylideneamino)-propionic acid methyl ester (4): a = 9.309(1) ?, b = 11.460(1) ?, c = 11.310(1) ?, β = 112.582(2)°,P2_1.(3R)-5,7-dimethyl-3-phenyl-2,3-dihydro-[1,4]oxazepinium trifluoroborate (5): a = 8.958(1) ?, c = 18.085(1) ?, P4₃. (2S, 3R)-3-methoxycarbonyl-2, 5,7-trimethyl-2, 3-dihydro-[1,4] oxazepin-4-ium trifluroborate (6): a = 8.626(1) ?, b = 11.597(1) ?, c = 13.733(19) ?, P2₁2₁2₁. 3-Methoxycarbonyl-5, 7-dimethyl-2, 3-dihydro- [1,4]-thiazepin-4-ium trifluoroborate (7): a = 13.737(1) ?, b = 6.244(1) ?, c = 16.041(1) ?, β = 104.927(2)°, P2₁/n.     

ZnCl2-Catalyzed [4+1] Annulation of Alkylthio-Substituted Enaminones and Enaminothiones with Sulfur Ylides

Concise construction of furan and thiophene units has played an important role in the synthesis of potentially bioactive compounds and functional materials. Herein, an efficient Lewis acid ZnCl₂ catalyzed [4+1] annulation of alkylthio-substituted enaminones is reported, that is, α-oxo ketene N,S-acetals with sulfur ylides to afford 2-acyl-3-aminofuran derivatives. In a similar fashion, [4+1] annulation of the corresponding enaminothiones, that is, α-thioxo ketene N,S-acetals, with sulfur ylides efficiently proceeded to give multisubstituted 3-aminothiophenes. This method features wide substrate scopes as well as broad functional group tolerance, offering a concise route to highly functionalized furans and thiophenes.     

Synthesis of Diastereoenriched α‐Aminomethyl Enaminones via a Brønsted Acid‐Catalyzed Asymmetric aza‐Baylis‐Hillman Reaction of Chiral N‐Phosphonyl Imines

An effective chiral GAP methodology for preparing α‐aminomethyl enaminones through a (R)‐CSA‐catalyzed asymmetric aza‐Baylis‐Hillman reaction is reported. Excellent yields and high diastereoselectivity could be obtained under mild conditions and convenient GAP techniques. The confirmations of the absolute configuration of N‐phosphonyl imine and chiral enaminone by X‐ray diffraction provides an explicit explanation of the chirality mechanism for GAP chemistry.     

(±)-CSA catalyzed one-pot synthesis of 6,7-dihydrospiro[indole-3,1′-isoindoline]-2,3′,4(1H,5H)-trione derivatives: easy access of spirooxindoles and ibophyllidine-like alkaloids

The domino dehydration/condensation/cyclization sequence reaction of cyclic enaminones with 3-hydroxy-3-ethoxycarbonylisoindolin-1-one derivatives has been successfully realized for the first time in toluene at 90 °C by using a catalytic amount of commercially available inexpensive (±)-CSA (30 mol %). Gratifyingly, this novel domino protocol provides good to excellent yields of previously unknown class of 1-aryl/alkyl-substituted 6,7-dihydrospiro[indole-3,1′-isoindoline]-2,3,4(1H,5H)-trione derivatives. Moreover, biologically attractive spirooxindoles and ibophyllidine-like alkaloids have been prepared.     

Synthesis and Reactivity of Enaminones: Synthesis of Some 1,3,4‐Thiadiazole Linked to Pyrazole,Pyridine, Benzimidazolopyrimidine,Pyrazolopyrimidine, Pyrazolotriazine and Triazolotriazine Derivatives

1,3,4‐Thiadiazole‐enaminone ( 6 ) was synthesized via reaction of the benzamide ( 5 ) with DMF‐DMA. The simple thiadiazole‐enaminone ( 6 ) was used as a synthetic precursor for the synthesis of a wide variety of new heterocyclic compounds, including the 5‐substituted‐1,3,4‐thiadiazole derivatives ( 7 ), ( 8 ), ( 16 ), ( 17 ) and ( 18 ), which were obtained via reactions of ( 6 ) with nitrogen nucleophiles. Also, reactions of enaminone ( 6 ) with carbon nucleophiles afforded the respective 1,3,4‐thiadiazoles ( 10a , 10b ). Diazotization of the benzamide ( 20 ) with the heteroaromatic amine salts gave the hydrazone derivatives ( 21 ) and ( 22 ). Cyclization of the latter hydrazones yielded the corresponding pyrazolotriazine and 1,2,4‐triazolotriazine derivatives ( 23 ) and ( 24 ), respectively. All newly synthesized compounds were elucidated by considering the data of both elemental and spectral analysis.     

Synthesis and structure of some azo coupled cyclic beta-enaminones

The reaction of 3-phenylaminocyclopent-2-en-1-one with 4-methyl, 4-methoxy and 4-chlorobenzenediazonium tetrafluoroborates was used to prepare the azo coupling products 3a-c. It was found that these compounds are present in both CDCl(3) solution and solid phase practically exclusively as (E)-3-phenylamino-2-(4-subst.phenyldiazenyl)cyclopent-2-en-1-ones with N--H...N intramolecular hydrogen bond. The substitution of the phenyl residue of the diazonium salt has no effect on the position of the tautomeric equilibrium. On the other hand, the compounds 4a, b formed by the reaction of 3-phenylamino-1H-inden-1-one with 4-methylbenzene- or benzenediazonium tetrafluoroborates exist in CDCl(3) solution and in solid phase as hydrazone compounds. In the solution they occur as a mixture of three forms, out of which two were identified as E/Z isomers with different types of hydrogen bonds. Compound 5 formed by the reaction of 3-amino-5,5-dimethylcyclohex-2-en-1-one with 4-methoxybenzenediazonium tetrafluoroborate is converted into a stable hydrochloride 5.HCl on standing in CHCl(3) solution; this product exhibits a high degree of delocalization of the positive charge. Its structure was studied by means of X-ray.     

New approaches to β-trifluoromethylated enone derivatives

β-Trifluoromethylated enaminones 1 were prepared stereospecifically or high stercoselectively in 31-92% yields from the reaction of Weinreb amides with trifluoropropynyl lithium, followed by quenching with H₂O in the presence of amine derivatives. β-Trifluoromethylated enaminone 1a was reacted with aryl or alkynyl Grignard reagents to give Michael addition products 5 at 0 °C, whereas addition-elimination adducts, β-aryl (or alkynyl)-β-trifluoromethylated enones 6, were obtained stereospecifically in 50-92% yields after stirring at room temperature for several hours.