5C + 1N] annulation: a novel synthetic strategy for functionalized 2,3-dihydro-4-pyridones

A novel and facile route to functionalized mono/bicyclic 2,3-dihydro-4-pyridones has been developed via formal [5C + 1N] annulation of readily available alpha-alkenoyl ketene-(S,S)-acetals with various aliphatic primary amines.     

5 + 1] annulation: a synthetic strategy for highly substituted phenols and cyclohexenones

A novel [5 + 1] annulation strategy is developed for the synthesis of highly substituted phenols and cyclohexenones from alpha-alkenoyl ketenedithioacetals and nitroalkanes.     

A heterocycle-forming double michael reaction. [5 + 1] annulation route to highly substituted and functionalized piperidines

[reaction: see text]. Nitrogen-containing tethered diacids, easily prepared by reductive alkylation of diethyl aminomalonate or ethyl cyanoglycinate, undergo double Michael reactions with 3-butyn-2-one to give highly functionalized and substituted piperidines (pipecolic acid derivatives) with surprisingly high stereoselectivity. The heterocyclic double Michael adducts can be induced to undergo further cyclizations to give a variety of azabicyclic and diazabicyclic compounds.     

Studies on oxidopyrylium [5+2] cycloadditions: toward a general synthetic route to the C12-hydroxydaphnetoxins

[Structure: see text] 12-hydroxydaphnetoxins, members of the structurally fascinating daphnane diterpene family, exhibit a wide range of significant biological activities. A general route to the BC-ring system of 12-hydroxy daphnetoxins is reported based on D-ribose. Depending on the choice of protecting groups and solvent, the oxidopyrylium-alkene [5+2] cycloaddition originating from A provides cycloadduct diastereomer B or C with good to excellent selectivity.     

Catalytic asymmetric [4+2] annulation initiated by an aza-rauhut-currier reaction: facile entry to highly functionalized tetrahydropyridines

Under control: The first example of chiral amino phosphine catalysts for the title reaction between vinyl ketones and N-sulfonyl-1-aza-1,3-dienes has been developed. Under ambient conditions, this protocol provides straightforward access to densely functionalized, enantioenriched tetrahydropyridines with high levels of sterecontrol in good to excellent yields.     

N-heterocyclic carbene-catalyzed cascade annulation reaction of o-vinylarylaldehydes with nitrosoarenes: one-step assembly of functionalized 2,3-benzoxazin-4-ones

The NHC-catalyzed reactions of ortho electron-deficient vinyl substituted arylaldehydes with nitrosoarenes were studied. The reactions produced multifunctional 2,3-benzoxazin-4-ones in good to excellent yields via a cascade aza-benzoin reaction between aldehyde and nitroso groups followed by an intramolecular oxo-Michael addition. The resulting 1-acetate substituted 2,3-benzoxazinones were transformed into a new type of β-hydroxycarboxylate derivatives or 3-oxo-1-isobenzofuranacetates, respectively, under different reductive conditions. This work not only provides a simple and efficient method for the construction of multifunctional 2,3-benzoxazin-4-ones of potential pharmacological interest, but also expands the application of NHC-catalyzed cascade reactions in the formation of carbon-heteroatom and heteroatom-heteroatom bonds.     

A facile [4+1] type synthetic route to thiophenes from dienol silyl ethers and elemental sulfur

A facile method for the synthesis of thiophene derivatives via the reaction of readily accessible dienol silyl ethers with elemental sulfur is described. Dienol silyl ethers and elemental sulfur, when heated at 180 °C in the presence of MS4A, provided 3-siloxythiophene derivatives in yields up to 98%. In this reaction, thiophene derivatives might be formed through 1,2-dithiines and eight-membered cyclic tetrasulfides.     

Synthesis of functionalized 2,3-dihydrothieno[2,3-d]pyrimidin-4(1H)-ones and their recyclization to 2,3-dihydrothieno[3,4-d]pyrimidin-4(1H)-ones

By the reaction of 6-aryl(alkyl)amino-5-cyano-2,3-dihydro-1,3-thiazin-4(10)-ones with α-halogenoketones in the presence of triethylamine, 2,3-dihydrothieno[2,3-d]pyrimidin-4(1H)-ones have been synthesized and their acid-catalyzed recyclization to 2,3-dihydrothieno[3,4-d]pyrimidin-4(1H)-ones has been found and studied. © 2006 Wiley Periodicals, Inc. Heteroatom Chem 17:104–111, 2006; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20181     

Three-component one-pot synthetic route to 2-amino-5-alkylidene-thiazol-4-ones

A fast and straightforward three-component reaction to 2-amino-5-alkylidene-thiazol-4-ones is described. The one-pot methodology, reported for the first time, involves Knoevenagel condensation of aromatic aldehydes and rhodanine followed by displacement of the thiocarbonyl sulfur with primary or secondary amines in the same reaction mixture. The reactions were performed using a dedicated microwave reactor, which enabled short reaction times and easy work-up.     

Facile and efficient one-pot synthesis of highly functionalized thieno[2,3-b]thiopyran-4-ones from beta-keto epsilon-xanthyl phosphonates

The one-pot synthesis of various functionalized thieno[2,3- b]thiopyran-4-ones from readily available beta-keto epsilon-xanthyl phosphonates has been accomplished by combining a Horner-Wadsworth-Emmons olefination with a base-induced intramolecular domino cyclization/thio-Michael addition. The use of cyclic ketones in this transformation allowed a facile access to novel spiro-type thieno[2,3- b]thiopyran structures.     

Convenient synthesis of functionalized thieno[2,3-d]pyrimidine-4-ones and thieno[2,3-b]pyridine-4-ones bearing a pyridine moiety with anticipated antioxidant activity

In the present study, ethyl 2-amino-4-methyl-5-(pyridin-2-ylcarbamoyl)thiophene-3-carboxylate (2) has been achieved using the Gewald's methodology and served as a synthon for the synthesis of various derivatives of thieno[2,3-d]pyrimidine-4-one and thieno[2,3-b]pyridine-4-one bearing a pyridine moiety via its reactions with the convenient chemical reagents. The antioxidant performance has been tested using the ABTS method and the results disclosed that thienopyrimidinone 5 and thienopyridinones 18 and 19 have the most potent antioxidant efficiency with inhibition percentage at 84.41%, 80.95%, and 76.93%, respectively, compared with ascorbic acid as a reference drug.     

An expedient phosphine-catalyzed [4 + 2] annulation: synthesis of highly functionalized tetrahydropyridines

Ethyl 2-methyl-2,3-butadienoate acts as a 1,4-dipole synthon and undergoes [4 + 2] annulation with N-tosylimines in the presence of an organic phosphine catalyst. The resulting adducts, ethyl 6-substituted-1-(4-tosyl)-1,2,5,6-tetrahydro-pyridine-3-carboxylates, are formed in excellent yields with complete regioselectivity. Mechanistic reasoning for this new annulation has led to an expansion of the reaction scope by employing ethyl 2-(substituted-methyl)-2,3-butadienoates to give ethyl 2,6-cis-disubstituted-1-(4-tosyl)-1,2,5,6-tetrahydro-pyridine-3-carboxylates with high diastereoselectivities.     

A new efficient route to imidazo[4,5-c]pyrazol-5-ones

The synthesis of imidazo[4,5-c]pyrazol-5-ones ( 6 ) is reported. 5-Amino-4-ethoxycarbonylaminopyra-zoles 3a-g when heated at 200° for 2 hours afford 6a-g. In a similar manner imidazo[4,5-c]pyrazol-5-one ( 6a ) is readily obtained from 4-amino-5-ethoxycarbonylaminopyrazole ( 5a ).     

Diastereoselective [4 + 4]-photocycloaddition reactions of pyran-2-ones: rapid access to functionalized 5-8-5 skeletons

Fused bicyclic pyran-2-ones with pendant furan side chains and an oxygenated stereogenic center adjacent to the pyranone ring oxygen were prepared via FeCl(3)-catalyzed Michael addition. Irradiation furnished the corresponding lactone-bridged tricyclic [4 + 4]-cycloadducts with good facial selectivity. Surprisingly, the major isomer resulted from approach of the furan from the same face as the protected alcohol. [reaction: see text]     

Methylenecyclopropane as C1 synthetic units: [1+4] cycloaddition via a nickel catalyst

Nickel-catalyzed reactions of methylenecyclopropanes and thioanhydrides afford sulfur-containing heterocyclic compounds via [1+4] cycloaddition. The reactions represent a new use for methylenecyclopropane as a possible one-carbon building block to replace carbon monoxide, isocyanides, and Fischer carbene complexes.     

Intramolecular [2+2]-cycloaddition of propargylic 2,3-allenoates for the efficient synthesis of 3-oxabicyclo[4.2.0]octa-1(8),5-dien-4-ones: a dramatic substituent effect

[2+2]-Cycloaddition reactions of propargylic 2,3-allenoates under conventional heating conditions afforded 3-oxabicyclo[4.2.0]octa-1(8),5-dien-4-ones, which contain both the biologically important 5,6-dihydropyran-2-one and cyclobutene units.     

[5C+1N]成环反应：吡啶-4(1H)酮类化合物的一种简便合成方法

用N,N-二甲基丙烯酰基二硫缩烯酮类化合物2与各种脂肪胺类化合物3在N,N-二甲基甲酰胺溶剂中60 ℃条件下,氮乙烯基发生分子内的亲核取代反应,通过[5C+1N]成环反应,合成了系列吡啶-4(1H)酮类化合物4,产率在75%~95%之间。     

A concise synthetic strategy to functionalized chromenones via [5+1] heteroannulation and facile C-N/C-S/C-O bond formation with various nucleophiles

A highly efficient strategy to 2,3-substituted chromen-4H-ones has been developed. The methodology involves unexpected intramolecular heteroannulation of readily accessible substituted 2-hydroxy-ω-nitroacetophenone with carbon disulfide in the presence K₂CO₃ followed by methylation with methyl iodide. These chromenones were further reacted with various nucleophiles such as amines, thiols, and alkoxide resulting in the facile C-N, C-S, and C-O bond formation. The scope and generality have been discussed.     

N-heterocyclic carbene-catalyzed [4 + 1] annulation of phthalaldehyde and imines

The diastereoselective synthesis of cis-2-amino-3-hydroxyindanones was realized by the N-heterocyclic carbene-catalyzed [4 + 1] annulation of phthalaldehyde and imines, which may involve a tandem aza-benzoin reaction and aldol reaction.     

Efficient synthesis of highly functionalized dihydropyrido[2,3-d]pyrimidines by a double annulation strategy from alpha-alkenoyl-alpha-carbamoyl ketene-(S,S)-acetals

A convenient and efficient synthesis of highly functionalized dihydropyrido[2,3-d]pyrimidines via a double [5 + 1] annulation strategy starting from easily available alpha-alkenoyl-alpha-carbamoyl ketene-(S,S)-acetals 1 and cheap reagents (NH4OAc, DMF, and POCl3) has been developed. In the first step of the double annulation route, 2-amino-3-carbamoyl-5,6-dihydro-4-pyridones 2 were created in high to excellent yields by a formal [5C + 1N] annulation reaction of ketene-(S,S)-acetals 1 with ammonia (from ammonium acetate). In the second step of the double annulation strategy, the highly functionalized dihydropyrido[2,3-d]pyrimidine derivatives, 7,8-dihydropyrido[2,3-d]pyrimidin-4(3H)-ones 3 (when R1 = aryl) and 7,8-dihydropyrido[2,3-d]pyrimidines 4 (when R1 = H), were constructed, respectively, in fair to good yields by reacting 2 with excessive Vilsmeier reagent (DMF/POCl3). A mechanism involved in the second [5 + 1] annulation step, including a formal [5 + 1] annulation and accompanied chlorovinylation, chloroformylation, amination, and aromatization reactions, is proposed.