Synthesis of 1,2-dihydro-4H-3,1-benzoxazine derivatives via ZnCl2 catalyzed cyclocondensation reaction

A short and facile synthesis of a series of 1,2-dihydro-4H-3,1-benzoxazine derivatives was accomplished in moderate to good yields via the novel cyclocondensation of substituted o-aminobenzonitrile with aldehydes or ketones catalyzed by ZnCl₂.     

Synthesis, stereochemical and conformational properties of trans-2,3-dihydro-2-methyl-3-(1,2,4-triazolyl)-4H-1-benzopyran-4-one oxime ethers

A convenient synthesis and structural characterization of (Z)- and (E)-trans-2,3-dihydro-2-methyl-3-(1,2,4-triazolyl)-4H-1-benzopyran-4-one oxime ethers has been achieved. By analysis of vicinal interproton coupling constants, it is believed that trans-2,3-dihydro-2-methyl-3-(1,2,4-triazolyl)-4H-1-benzopyran-4-ones which exist predominantly in the diequatorial half-chair or sofa conformation was found to exist predominantly in the diaxial orientation upon conversion to the corresponding oxime ether derivatives.     

Highly diastereoselective cycloaddition reactions of variously substituted 1-thia- and 1-thia-3-aza-buta-1,3-dienes. Synthesis of enantiomerically pure 5,6-dihydro-4H-[1,3]thiazines and 3,4-dihydro-2H-thiopyrans

The cycloaddition of 2- or 2,3-substituted 1-thia- and 1-thia-3-aza-4-dimethylamino-buta-1,3-dienes with various dienophiles in the presence of a Lewis acid provides a rapid and diastereoselective access to the 3,4-dihydro-2H-thiopyran and 5,6-dihydro-4H-[1,3]thiazine backbones. The generally observed trans relationship between the two newly created strereogenic centres was demonstrated to be the expression of a thermodynamic control of the reaction. The use of chiral dienophile derived from chiral oxazolidin-2-ones allowed us to prepare enantiopure 5,6-dihydro-4H-[1,3]thiazines and 3,4-dihydro-2H-thiopyrans. In the asymmetric synthetic process the chiral auxiliary removal step was best accomplished in the presence of samarium triflate in methanol.     

A convenient and mild synthesis of new 2-aryl-3-hydroxy-6,7-dihydro-1H-indol-4(5H)-ones via a one-pot,three-component reaction in water

A simple and convenient synthesis of 2-aryl-3-hydroxy-6,7-dihydro-1H-indol-4(5H)-ones is achieved in high yields via the one-pot, three-component reaction of arylglyoxals, 1,3-cyclohexanedione, and ammonium acetate in water under reflux conditions.     

A novel and facile synthesis of 2-(cyclohexylamino)-6,7-dihydro-3-aryl-1H-indole-4(5H)-ones via a one-pot multi-component reaction

A simple and efficient synthesis of 2-(cyclohexylamino)-6,7-dihydro-3-aryl-1H-indole-4(5H)-ones was achieved via a one-pot multi-component reaction of cyclohexyl isocyanide, an aldehyde, a 1,3-dicarbonyl compound, and ammonium acetate in the presence of a catalytic amount of KHSO₄ in acetonitrile.     

Reaction between isocyanides and dialkyl acetylenedicarboxylates in the presence of 2,4-dihydro-3H-pyrazol-3-ones. One-pot synthesis of highly functionalized 7-oxo-1H,7H-pyrazolo[1,2-a]pyrazoles

The reactive 1:1 intermediate produced in the reaction between isocyanides and dialkyl acetylenedicarboxylates was trapped by 2,4-dihydro-3H-pyrazol-3-ones to yield highly functionalized 7-oxo-1H,7H-pyrazolo[1,2-a]pyrazoles in fairly good yields.     

A simple and one-pot synthesis of 2,3,4,5-tetrasubstituted 4,5-dihydro-3H-1,4-benzodiazepines

2,3,4,5-Tetrasubstituted 4,5-dihydro-3H-1,4-benzodiazepines were synthesized in one-pot by a new sequential Ugi 4CC/Staudinger/aza-Wittig reaction, starting from easily accessible o-azidobenzaldehyde, α-amino ketone hydrochloride, isocyanide and carboxylic acid.     

Synthesis of 6,7-dihydro-5H-dibenzo[c,e]azepines and biaryls by palladium-catalyzed Ullmann reaction

A novel palladium-catalyzed Ullmann protocol is described for the synthesis of 6,7-dihydro-5H-dibenzo[c,e]azepines and biaryls. In the presence of Pd(OAc)₂ and KOAc, intramolecular or intermolecular Ullmann coupling of aryl halides proceeds efficiently under ligand-free and aerobic conditions to afford the corresponding 6,7-dihydro-5H-dibenzo[c,e]azepines and biaryls in moderate to excellent yields.     

Synthesis of 2H-1,5-benzodioxepin and 2,5-dihydro-1,6-benzodioxocin derivatives via ring-closing metathesis reaction

The synthesis of various 2H-1,5-benzodioxepin and 2,5-dihydro-1,6-benzodioxocin derivatives is described. The key step involves the construction of seven- and eight-membered rings via ring-closing metathesis reaction.     

One-pot synthesis of 4,5-dihydro-1H-pyrrol-3-carboxamide derivatives via a four-component reaction

An effective route to functionalized 4,5-dihydro-1H-pyrrol-3-carboxamide derivatives is described. This involves reaction of N-alkyl-3-oxobutanamides, which result from the addition of an amine to the diketene, and a primary amine in the presence of dibenzoylacetylene. The 1,3-dicarbonyl compounds obtained from the addition of an amine to diketene were trapped with a primary amine to produce (Z)-3-(alkylamino)-N¹-alkyl-2-butenamide, which reacts with dibenzoylacetylene to produce 4,5-dihydro-1H-pyrrol-3-carboxamide derivatives.     

Simultaneous synthesis of 4,5-dihydro-3H-azepines and 3H-azepines, bearing alkoxy and alkylsulfanyl substituents, through metallation of 2-aza-1,3,5-trienes by t-BuOK

A new range of alkoxy- and alkylsulfanyl-substituted 4,5-dihydro-3H-azepines and 3H-azepines have simultaneously been obtained from conjugated 2-aza-1,3,5-trienes by treatment with t-BuOK under mild reaction conditions (THF/DMSO, ∼−30 °C, 30 min). One-pot synthesis of 1-aza-1,3,4-trienes from α-lithiated alkoxyallenes, isopropyl isothiocyanate and alkyl iodides, followed by the thermally induced sigmatropic [1,5]-H shift, easily leads to starting 2-aza-1,3,5-trienes. The reaction proceeds via generation and [1,7]-electrocyclization of azatrienyl anions and represents a novel simple approach to both azacycloheptadienes and azacycloheptatrienes.     

Copper(II) complexes containing chiral substituted 2-(4-isopropyl-4-methyl-4,5-dihydro-1H-imidazol-5-one-2-yl)pyridine ligands: Synthesis, X-ray structural studies and asymmetric catalysis

New chiral N,N-bidentate ligands derived from substituted 2-(4-isopropyl-4-methyl-4,5-dihydro-1H-imidazol-5-one-2-yl)pyridines have been prepared and characterised by means of ¹H, ¹³C NMR spectroscopy and optical rotation. Their Cu(II) complexes were characterized by means of elemental analysis, ¹H NMR spectroscopy and MS. By means of X-ray diffraction, molecular geometry of the complex of 2-(1-methyl-4-isopropyl-4-methyl-4,5-dihydro-1H-imidazol-5-one-2-yl)pyridine with copper(II) chloride was determined. The complex exhibits heterochiral dimeric arrangement of two square pyramids with one terminal and one bridge-forming chlorine atoms and two nitrogen atoms in the bases of the pyramids. The tops of these pyramids are formed by the remaining chlorine atoms. The complexes prepared catalyse the Henry reaction with the overall yields of 41-97% and with the maximum enantioselective excess of 19%.     

Traceless solid-phase synthesis of 1,4-disubstituted-6-nitro-3,4-dihydro-1H-quinoline-2-ones

A traceless solid-phase route to 1,4-disubstituted-6-nitro-3,4-dihydro-1H-quinazolin-2-ones is described. N-Alloc-3-amino-3-(2-fluoro-5-nitrophenyl)propionic acid was tethered to Rink resin via its carboxylic group. The protected amine was coupled with an organic acid after Alloc-deprotection and the arylfluorine was displaced with a primary amine to generate a resin-bound aniline with two diversity points. The aniline was released via cleavage to produce the desired products in high yield and purity.     

A new efficient method for the synthesis of 3,4-dihydro-2H-1,4-benzoxazines via iodocyclization

An efficient approach for the synthesis of 3,4-dihydro-2H-1,4-benzoxazine derivatives is described by molecular iodine- mediated cyclization. The reaction condition is very simple, offers easy isolation, and affords good to excellent yields of the products.     

TMSI mediated Prins-type cyclization of ketones with homoallylic and homopropargylic alcohol: synthesis of 2,2-disubstituted-, spirocyclic-4-iodo-tetrahydropyrans and 5,6-dihydro-2H-pyrans

The Prins-type cyclization of ketones with homoallylic and homopropargylic alcohols in the presence of TMSI generated in situ from TMSCl and NaI produced 2,2-disubstituted- or spirocyclic-4-iodo-tetrahydropyrans and spirocyclic-4-iodo-5,6-dihydro-2H-pyrans in good yields. These iodopyrans are reported for the first time.     

Chemoenzymatic preparation of optically active 4-aryl-5-carboxy-6-methyl-3,4-dihydro-2(1H)-pyridone derivatives

A series of racemic 4-aryl-5-(tert-butoxycarbonyl)-6-methyl-3,4-dihydro-2(1H)-pyridones have been prepared by means of a modified Hantzsch reaction using commercially available starting materials. An easy removal of the tert-butyl group of these pyridones and subsequent reaction with cesium carbonate and chloromethyl 2-methylpropanoate provided us suitable substrates (±)-5 to be used in lipase-catalyzed hydrolysis reactions. Lipase B from Candida antarctica (CAL-B) was the most adequate lipase in the hydrolysis of (±)-5. Despite the low enantioselectivity values obtained (E≤12), several optically active pyridone derivatives were finally isolated with high enantiomeric excesses (ee≥91%) and moderate yields.     

Reaction of benzoyl chlorides with Huisgen's zwitterion: synthesis of functionalized 2,5-dihydro-1H-pyrroles and tetrasubstituted furans

The 1:1 intermediate generated by the addition of alkyl(aryl) isocyanides to dimethyl acetylenedicarboxylate is trapped by benzoyl chloride to yield functionalized 2,5-dihydro-1H-pyrroles. The presence of electron-withdrawing groups at the para position of benzoyl chloride leads to tetrasubstituted furans. The structures of these products were confirmed by single-crystal X-ray diffraction studies.     

Synthesis of 2-diphenylphosphinoyl-3,5-diaryl-3,4-dihydro-2H-telluropyrans by reaction of chalcones with bis[(diphenylphosphinoyl)methyl]telluride

The NaH-promoted tandem Michael addition/intramolecular Wittig-Horner reaction of bis[(diphenylphosphinoyl) methyl]telluride with chalcones stereoselectively afforded trans-2-diphenylphosphinoyl-3,5-diaryl-3,4-dihydro-2H-telluropyran derivatives in 51-72% yield, under mild conditions.     

Synthesis and pharmacological evaluation of 6a,7-dihydro-6H,13H-pyrazino[1,2-a;4,5-a′]diindole analogs as melatonin receptor ligands

The synthesis of two melatonin-derived analogs of the novel 6a,7-dihydro-6H,13H-pyrazino[1,2-a;4,5-a′]diindole ring system is described. The non-methoxy and methoxy analogs, 4a and 4b were prepared in seven steps starting from indoline-2-carboxylic acid 5a and 5-methoxyindoline-2-carboxylic acid 5b, respectively. While 4a exhibited micromolar affinities for both melatonin receptors, the methoxy analog 4b displayed moderate affinity for MT₂ receptors (K_i=0.41 μM) being 4.4-fold higher than for the MT₁ subtype.     

Ring-closing metathesis for the synthesis of 2H- and 4H-chromenes

Six 4H-chromenes were synthesized from substituted phenols using vinylstannylation and ring-closing metathesis (RCM) as key steps. In addition, a different approach involving amongst other steps, an aryl allyl isomerization and RCM afforded a set of seven 2H-chromenes from phenolic precursors.