Alkyne hydroamination triggered cyclizations: A powerful tool for the construction of biologically important structural motifs

This review focuses mainly on recent endeavors in the field of cyclizations triggered by the catalytic hydroamination (formal or direct) of alkynes. The new strategies developed offer an efficient and convenient entry to several heterocycles of biological importance.     

Properties of a Ring Critical Pointas Measures of Intramolecular H-Bond Strength

Summary.  The topological parameters derived from the Bader theory such as the electron density and its Laplacian at the ring critical point (RCP) are analysed here as possible measures of the H-bond stength for intramolecular H-bonds. The parameters of RCP correlate well with the other properties of intramolecular H-bonds which are known as good measures of the H-bond strength. The calculations were performed on two samples of compounds with intramolecular H-bonds: the derivatives of malonaldehyde and the derivatives of o-hydroxybenzaldehyde. MP2 and HF calculations were carried out using a 6-311++G^** basis set. E-mail: slagra@krysia.uni.lodz.pl Received February 18, 2002; accepted (revised) May 27, 2002     

Crystal chemistry of protonated 1,2-bis(di-R-aminomethyl)benzenes. Part V. [1,2-bis(diethylaminomethyl)-3,6-dichlorobenzene:1,2-bis(diethylaminomethyl)-3,4,6-trichlorobenzene]perchlorate mixed crystals

The mixed crystals of 1,2-bis(diethylaminomethyl)-3,6-di- and 3,4,6-trichloro-benzene perchlorate at 0.5:0.5 ratio have been studied using X-ray diffraction and FT-IR spectroscopy. The molecules of di- and tri-chloro derivatives are distributed randomly in the crystal lattice; however, this disorder manifested mainly by a partial occupation of the chlorine atom at C(4) and by relatively big atomic temperature parameters even at 99 K, particularly for the oxygens of the perchlorate anion. The proton in the [NHN]⁺ bond refined close to the equidistant position between the nitrogens. The conformations of the diethylaminomethyl substituents are pseudo-symmetrical relative to the plane and twofold axis passing through the midpoint of the hydrogen bond. The IR spectrum of the crystals shows a broad intense band and an intense continuous absorption indicating relatively high proton polarizability in the intramolecular hydrogen bond. In acetonitrile and in chloroform, the proton in the intramolecular hydrogen bond also shows a very high proton polarizability demonstrated by the continuous absorption in the IR spectrum.     

Photoreaction of 2′-chloro-4-R-benzanilide: synthesis of 2-(4-R-phenyl)-1,3-benzoxazole and 9-R-phenanthridin-6(5H)-one (R=H, CH3, CH3O)

The UV photolysis of 2′-chloro-4-R-benzanilides in acetonitrile solution under nitrogen atmosphere leads to the formation of intramolecular photocyclization products (9-R-phenanthridin-6(5)-one, 20–30%), along with the minor photoreduction, photo-Fries, and intramolecular photosubstitution products. The photoreaction of 2′-chloro-4-R-benzanilide in acetonitrile solution containing 10% of water or aqueous sodium hydroxide however gives 2-(4-R-phenyl)-1,3-benzoxazole as a major product (30%) along with the photoreduction, photo-Fries and intramolecular photocyclization products.     

Stereoselective intramolecular cyclization of γ-allylbenzamide via π-allylpalladium complex catalyzed by Pd(0)

An efficient procedure for synthesizing oxazines was developed by the palladium(0)-catalyzed intramolecular cyclization of a benzamide through a π-allylpalladium (II) complex. Interestingly, the diastereoselectivity of oxazine ring formation was dominantly controlled by the bulkiness of various protecting groups on the secondary alcohols.     

A novel biomimetic synthesis of (S)-(−)-zearalenone: via macrocyclization and transannular aromatization

On heating, a hydroxy-keto-dioxinone underwent retro-Diels-Alder fragmentation and the resultant α,γ-diketo-ketene was efficiently trapped intramolecularly by a secondary alcohol to provide a macrocyclic triketo-lactone. Following ketal hydrolysis, transannular aromatization gave the resorcylate natural product, (S)-(−)-zearalenone.     

Palladium-catalyzed cyclization of 1,6-enyne with 2-bromoarylaldehyde: domino sequence to [5-7-6] tricyclic ring systems

A domino sequence of cyclization of 1,6-enyne with 2-bromoarylaldehyde followed by the intramolecular Aldol-condensation has been realized in the presence of 5 mol % of palladium catalyst. This sequence provides a convenient protocol to access polycyclic ring systems with readily available starting materials under simple Pd(0)-catalyzed conditions. The intramolecular Aldol-condensation has been proposed as the key step for the catalytic cycle.     

Photochemistry of benzene and quinoxaline fused Δ-1,2,3-triazolines and their trapping products

The benzene and quinoxaline fused Δ²-1,2,3-triazolines 1a and 1b were synthesized in good yields using Knoevenagel condensation and intramolecular 1,3-dipolar cycloaddition as two of the key reactions. Photolysis (254 nm) of Δ²-1,2,3-triazoline 1a or 1b in acetonitrile led to the homolytic cleavage of nitrogen that generated diethyl diazomalonate 7, highly reactive intermediates aziridines 8a,b, and isoindoles B. The latter two species subsequently underwent rearrangement to give the nitrogen extrusion products 9a,b, and polymers. Furthermore, the reactive intermediates were trapped by dienophiles to give the corresponding cycloadducts. Subsequent rearrangement of the N-bridged cycloadducts gave N-substituted pyrrolo[3,4-b]quinoxalines 12b and 15b in 6% and 9% yields, respectively. Irradiation of 1a in the presence of fumaronitrile led to the isolation of cycloadduct 16a with retention of stereochemistry. Thermal reaction of 1b gave more nitrogen extruded product 9b (58-63% yield) than that by photolysis (5-23% yield), which implied that zwitterionic intermediate might be involved in the former.     

An investigation of structure-reactivity relationships of δ-alkenyl oximes; competitive thermal reactions leading to cyclic nitrones and/or N-unsubstituted bicyclic isoxazolidines

Thermal reactions of C-aryl δ-alkenyl oximes give N-unsubstituted bicylic lactone, lactam and pyrrolidine fused isoxazolidines by an intramolecular oxime olefin cycloaddition pathway (IOOC) and/or cyclic nitrones by an azaprotio cyclotransfer (APT) route; a number of factors, including the nature of the aryl group, the oxime geometry and the structure of the linker between the oxime and the terminal alkene, contribute to the competition.     

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.