Synthesis of 2,7-Diazabicyclo[3.3.0]octane and 2,7-Diazabicyclo[3.3.0]oct-4-ene Derivatives via Cyclization Reaction and Julia Reaction

2,7-Diazabicyclo[3.3.0]octan-4-ol (1) and 2,7-diazabicyclo[3.3.0]oct-4-ene (2) are synthesized by the desulfonylation using Mg-HgCl₂(cat.) of β-hydroxy sulfone derivatives which have been prepared via cyclization of sulfone ester derivative.     

1,4-Diazabicyclo[2.2.2]octane as an Efficient Catalyst for a Clean,One-Pot Synthesis of Tetrahydrobenzo[b]pyran Derivatives via Multicomponent Reaction in Aqueous Media

1,4-Diazabicyclo[2.2.2]octane (DABCO) has been used as a mild and efficient catalyst for the synthesis of various tetrahydrobenzo[b]pyran derivatives via a one-pot, three component condensation of aromatic aldehydes, dimedone, and active methylene compounds. This method provides several advantages: a simple workup procedure, environmental friendliness, neutral conditions, and good yields. In addition, water or 50% aqueous ethanol was chosen as a green solvent.

Efficient synthesis of (S,S)-2,8-diazabicyclo[4.3.0]nonane

An efficient synthetic route for moxifloxacin chiral intermediate via five steps was established. First, dehydration, N-acylation, and cyclization were combined in one pot to meet the industrial requirement. Then relatively low hydrogen pressure was employed in the catalytic hydrogenation reaction with high yield. Isopropanol/water system was used in resolution, which guaranteed high yield and perfect optical purity. The racemic process conducted by manganese dioxide and Pd/C successfully converted the undesired enantiomer into the racemate and hence the total yield increased remarkably. Furthermore, mild hydrogen transfer catalytic hydrogenation method was utilized in debenzylation process instead of high-pressure hydrogenation. Total yield of 39.0% was achieved, which was much higher than that of 29.0% in literature.     

Synthesis of 2,7-Diazabicyclo[3.2.1]oct-3-ene Derivatives

Russian Journal of Organic Chemistry - Tetracyanoethylene adducts with ketones, 4-oxoalkane-1,1,2,2-tetracarbonitriles reacted with hydrogen chloride or phosphorus(III) chloride in 1,4-dioxane to...     

A Facile and Efficient Synthesis of Thieno[2,3-c]furans and Furo[3,4-b]indoles via a Pummerer-Induced Cyclization Reaction

The alpha-thiocarbocation generated from the Pummerer reaction of an o-heteroaroyl-substituted sulfoxide is intercepted by the adjacent keto group to produce an alpha-thio-substituted heteroaromatic isobenzofuran. In the presence of a suitable dienophile, the reactive o-xylylene undergoes a Diels-Alder cycloaddition followed by an acid-catalyzed ring-opening and aromatization to give heteroaromatic naphthalene derivatives. This one-pot procedure occurs smoothly with electron-deficient dienophiles. The tandem Pummerer cyclization-cycloaddition sequence also occurs intramolecularly using unactivated alkenyl tethers of variable length. With acetylenic dienophiles, the primary cycloadducts undergo in situ ring-opening to produce hydroxynaphthalene derivatives. In the absence of a dienophile, it was possible to prepare 4-(ethylthio)-6-phenylthieno[2,3-c]furan and 1-ethyl-4-(phenylsulfonyl)-4H-furo[3,4-b]indole. Various synthetic approaches were used for the preparation of the requisite thiophene- and indole-derived sulfoxide precursors. The facility of the tandem Pummerer-Diels-Alder reaction was very dependent on the experimental conditions used to promote the reaction. The best results were achieved by employing a mixture of acetic anhydride and toluene which contained a catalytic quantity of p-toluenesulfonic acid. The presence of the acid effectively drives the reaction in the desired direction by preventing formation of the acetoxy sulfide, which corresponds to the normal Pummerer product.     

Synthesis of 2-Arylpyrimido[4,5-b]porphyrins via Cyclization Reaction with Ammonia

A facile synthetic strategy for the synthesis of a new series of β,β’-fused 2-arylpyrimido[4,5-b]porphyrins has been developed by using condensation cyclization reaction with ammonia. 2-Aroylamino-3-formylporphyrins were synthesized from 2-aroylaminoporphyrins under Vilsmeier–Haack reaction conditions, which were then efficiently converted to the corresponding 2-arylpyrimido[4,5-b]-5,10,15,20-tetrakis(4-chlorophenyl)-porphyrins via a condensation cyclization reaction. The nickel(II), copper(II), free-base and zinc(II) analogues of 2-arylpyrimido[4,5-b]porphyrins were successfully synthesized in 65–72 % yields and structurally characterized on the basis of spectral data analysis. On photophysical evaluation, 2-arylpyrimido[4,5-b]porphyrins demonstrated a 12–19 nm bathochromic shift in their electronic absorption spectra and up to 10 nm red shift in their emission spectra as compared to the simple meso-(tetrakis(4-chlorophenyl))porphyrins due to the extended π-conjugation.     

Convenient Synthesis of Indene Derivatives via Intramolecular Friedel-Crafts Cyclization of Tetraaryl Substituted 1,3-Butadienes

A convenient and efficient method for the highly regioselecfive synthesis of indene derivatives 4 and 5 from tetraaryl substituted 1,3-butadienes 3 was described. The method involves an intramolecular Friedel-Crafts cyclization and a corresponding double-bond positional shift of isomers 4 and 5 in the presence of different Lewis acids under mild conditions with higher than 90% yields.     

Efficient Asymmetric Synthesis of Pumiliotoxin C via Intramolecular [4+2] Cycloaddition

An efficient asymmetric synthesis in nine steps of natural (−)‐pumiliotoxin C ( 1 ), a decahydroquinoline alkaloid found in the skin of Central American frog species, is presented. The enantiomerically pure starting material (S)‐norvalinol ( 3 ), obtained from commercial (S)‐norvaline, was cyclized in a one‐pot procedure to the tosylated aziridine 5 . Ring opening with propargylmagnesium bromide led to the acetylenic sulfonamide tosylamide 6 , free of the allenic isomer. Compound 6 was methylated on the acetylenic C‐atom, reduced, and deprotected with Na in liquid NH₃ to give the (E)‐configured unsaturated amine 8 , which was condensed with crotonaldehyde to the imine 9 and N‐acylated with isobutanoyl chloride to the key intermediate 2 . Intramolecular Diels‐Alder reaction furnished a diastereoisomeric mixture of N‐protected octahydroquinolines 10 . After catalytic hydrogenation and cleavage of the amide, natural 1 was obtained as the main product in 25% overall yield; 3.2% of its isomer 11 with the inverse configurations in position 4a, 5, and 8a was also isolated.     

Enantioselective Synthesis of Bicyclo[3.2.1]octadienes via Palladium-Catalyzed Intramolecular Alkene-Alkyne Coupling Reaction

Bicyclo[3.2.1]octadiene compounds and derivatives exist in a number of natural products and bioactive compounds. Nevertheless, catalytic enantioselective protocols for the synthesis of these skeletons have not been disclosed. Herein we reported a palladium-catalyzed asymmetric intramolecular alkene-alkyne coupling of alkyne-tethered cyclopentenes, affording a library of enantionenriched bicyclo[3.2.1]octadienes in excellent yields and enantioselectivities (mostly >99 % ee). Moreover, the products could undergo an unusual iodination-induced 1,2-acyl migration, forming iodinated bicyclo[3.2.1]octadienes with three vicinal stereocenters. The enone and isolated olefin motifs embedded in the products provide useful handles for downstream elaboration.     

Synthesis of Functionalized 2,3-Dihydro-5H-[1,3]thiazolo[2,3-b]quinazolin-5-one via Intramolecular Electrophilic Cyclization

Russian Journal of Organic Chemistry - 3-(2-Methylprop-2-en-1-yl)-2-sulfanylidene-7-(trifluoromethyl)-2,3-dihydroquinazolin-4(1H)-one reacted with halogens (bromine and iodine), chalcogen...     

乙酸酐促进的[3+3]环化反应合成2-喹啉酮衍生物

2-喹啉酮结构单元广泛存在于天然产物和药物活性分子中,并且是重要的杂环合成砌块.建立了一种乙酸酐促进下,环状β-烯胺酮和丙二酸通过[3+3]环合反应构建2-喹啉酮化合物的新方法,产率为70％～87％.该方法具有原料简单易得、操作简便、路线简洁、目标化合物可修饰性强等优点.     

Regioselective and Stereoselective Synthesis of Pyridine‐Fused Benzoxepine Derivatives by Intramolecular Reductive Heck Cyclization [1]

An efficient method for the synthesis of 6,11‐dihydro[2]benzoxepino[4,3‐b]pyridine derivatives via Pd(0) catalyzed intramolecular reductive Heck cyclization is reported. The method offers the regioselective and stereoselective synthesis of highly functionalized pyridine‐fused benzoxepine derivatives in 75–85% yields under mild conditions. Chemoselective Sonogashira coupling is utilized for the synthesis of cyclization precursors. The stereochemistry of the exocyclic double bond of 6,11‐dihydro[2]benzoxepino[4,3‐b]pyridine derivatives is confirmed from single crystal X‐ray diffraction. The absence of N–Pd(II) interaction results in a reverse stereochemistry of the exocyclic double bond of dibenzoxepine derivative.     

Efficient Catalytic Synthesis of Condensed Isoxazole Derivatives via Intramolecular Oxidative Cycloaddition of Aldoximes

The intramolecular oxidative cycloaddition reaction of alkyne- or alkene-tethered aldoximes was catalyzed efficiently by hypervalent iodine(III) species to afford the corresponding polycyclic isoxazole derivatives in up to a 94% yield. The structure of the prepared products was confirmed by various methods, including X-ray crystallography. Mechanistic study demonstrated the crucial role of hydroxy(aryl)iodonium tosylate as a precatalyst, which is generated from 2-iodobenzoic acid and m-chloroperoxybenzoic acid in the presence of a catalytic amount of p-toluenesulfonic acid.     

1,5-二氮杂二环[4.3.0]-壬-5-烯与全氟烷基炔酸甲酯的Michael加成反应

1,5-二氮杂二环[4．3．0]-壬-5-烯(DBN)与全氟烷基炔酸甲酯发生Michael加成反应,生成的中间体发生分子内缩合产生了三环化合物。其结构经元素分析,IR,MS和核磁共振氢谱、碳谱,二维核磁共振^13C-^1H cosy谱,二维核磁共振^1H-^1H cosy谱确认。对反应机理也进行了探讨。     

Facile Synthesis of 2H-Benzo[h]Chromenes via an Arylamine-Catalyzed Mannich Cyclization Cascade Reaction

A simple arylamine-catalyzed Mannich-cyclization cascade reaction was developed for facile synthesis of substituted 2H-benzo[h]chromenes. The notable feature of the process included the efficient generation of ortho-quinone methides (o-QMs) catalyzed by a simple aniline. The mild reaction conditions allowed for a broad spectrum of 1- and 2-naphthols and trans-cinnamaldehydes to engage in the cascade sequence with high efficiency.     

Synthesis of [1,2,3]Triazolo[5,1-a]isoquinoline Derivatives via a Selective Cascade Cyclization Sequence of 1,2-bis(Phenylethynyl)benzene Derivatives

A direct, concise, synthetic method for the generation of [1,2,3]triazolo[5,1-a]isoquinoline derivatives, using a selective cascade cyclization of unsymmetrical substituted 1,2-bis(phenylethynyl)benzene derivatives with NaN₃, has been developed. The reaction gave different substituted [1,2,3]triazolo[5,1-a]isoquinolines in moderate to good yields. It was found that the substituents on the alkynes were important for the selectivities of the cascade cyclization sequences.     

1-氮杂-2,8-二氧杂二环[3.3.0]-辛烷类化合物合成的新方法

以苯基-3,5-二(甲氧基羰基)-2-异(口恶)唑啉-N-氧化物为偶极体,丙烯酸乙酯为亲偶极体,通过[3+2]环加成反应,简便地合成了含有多官能团的1-氮杂-2,8-二氧杂二环[3.3.0]-辛烷类化合物。该反应条件温和,产率较高(50%～93%).化合物的结构经元素分析,¹H NMR,¹³C NMR,IR和MS确认和表证,并对其波谱性质进行了讨论。     

Diastereoselective Synthesis of 1,10-Dihydropyrrolo [ 1,2-a] [1,10]phenanthroline Derivatives via 1,3-Dipolar Cycloaddition Reaction

The functionalized 1,10-dihydropyrrolo[1,2-a][1,10]phenanthroline derivatives were synthesized in good yields and with high diastereoselectivity by 1,3-dipolar cycloaddition reactions of N-phenacylphenanthrolinium bromides or N-ethoxycarbonylmethylene phenanthrolinium bromide with various nitrostyrenes in acetonitrile at room temperature in the presence of triethvlamine,     

One Pot Spiropyrazoline Synthesis via Intramolecular Cyclization/Methylation

Regioisomeric spiropyrazolines were synthesized through a tandem intramolecular cyclization/methylation reaction of a functionalized 5,5-disubstituted pyrazoline in one reaction vessel. The 5,5-pyrazolines were constructed through a 1,3-dipolar cycloaddition reaction of aromatic ring containing nitrile imines and a disubstituted geminal alkene. An evaluation of the relative location of the nucleophilic and electrophilic functional groups on the pyrazoline was performed in order to ascertain the best pyrazoline system for the intramolecular cyclization/methylation reaction. Higher spiropyrazoline isolated yields were realized from pyrazolines with the electrophilic ester located further away from the pyrazoline when compared to pyrazolines with a directly bonded ester.