Addition Intramolecular Cyclization Research Articles

A near-infrared fluorescence turn-on probe based on Michael addition-intramolecular cyclization for specific detection of cysteine and its applications in environmental water and milk samples and living cells.

Owing to its important biological functions in many physiological and pathological processes, it is necessary to develop efficient and appropriate detection methods for monitoring the levels of Cys in biological systems. Based on this, a novel rhodol-isophorone derivative (RHI) was designed and synthesized as a reaction-based fluorescence probe for specific detection of Cys with high sensitivity and large Stokes shift (155 nm). This probe was composed of an acrylate moiety (recognition group) and a rhodol-isophorone derivative (fluorophore). Probe RHI could react with Cys rapidly (15 min) with a 100-fold fluorescence enhancement. The limit of detection value was calculated to be 0.168 μM. When Cys was added, the color of the probe RHI solution turned from yellow to blue, indicating that Cys could be monitored by the naked eye. In addition, probe RHI was successfully utilized for detecting Cys in environmental water and milk samples. More importantly, the probe could be applied to imaging Cys in living cells with low cytotoxicity and good biocompatibility.

Reaction of Bromoenones with Amidines: A Simple Catalyst-Free Approach to Trifluoromethylated Pyrimidines

A facile one-pot synthesis of trifluoromethylated pyrimidines has been achieved by the treatment of fluorinated 2-bromoenones with aryl- and alkylamidines. The assembly of pyrimidine core proceeds by the cascade reactions via aza-Michael addition–intramolecular cyclization–dehydrohalogenation/dehydration sequence. This strategy is featured by high selectivity and mild reaction conditions giving the target heterocycles in high yields (up to 99%). The unique influence of trifluoromethyl group on the reaction path is demonstrated.

Cu(I)-catalyzed cascade intramolecular cyclization of 2-propynol phenyl azides and diarylphosphine oxides for the synthesis of bisphosphorylated indole derivatives

The [Cu(OTf)]2·C6H6 catalyzed cascade intermolecular addition–intramolecular cyclization reaction of easily prepared 2-propynol phenyl azides and diarylphosphine oxides was developed. This novel reaction leads to simultaneous formation of one C–N and two C–P bonds in a single step to give bisphosphorylated indole derivatives under mild conditions in moderate to good yields.

Synthesis of (E)-4,5-Dihydro-1H-Pyrazoles via Tandem Intermolecular Addition–Cyclization of N-Propargylic Sulfonylhydrazones

A new strategy for the synthesis of (E)-4-benzylidene-4,5-dihydro-1H-pyrazoles through tandem intermolecular addition–intramolecular cyclization of N-propargylic sulfonylhydrazones has been developed. In this study, we firstly report that N-propargylic sulfonylhydrazones react with electrophilic reagents to afford 4-substituted pyrazole derivatives.

ChemInform Abstract: MCPBA‐Promoted Tandem Michael Addition—Intramolecular Cyclization of 2‐Azido‐β‐amino Esters: Single Pot, Convenient Access to 1,2,4,5‐Tetrasubstituted Imidazoles.

AbstractAttempts upon chromatographic separation of the diastereomeric starting material fail.

ChemInform Abstract: Application of N,3‐Diaryl‐3‐oxo‐propanethioamide in Synthesis: An Efficient and Mild Domino Approach to Highly Substituted Fused Chromenones.

A convenient and rapid synthesis of hitherto unknown 3-aroyl-4-aryl-2-phenylamino-4H-benzo[g]chromene-5,10-diones in high yield from β-aroyl-thioacetanilide, aromatic aldehyde, and 2-hydroxy-1,4-naphthoquinone via InCl3 catalyzed one-pot three-component tandem Knoevenagel condensation–Michael addition–intramolecular cyclization–elimination reaction sequence is disclosed for the first time. This domino protocol has been used to obtain highly substituted pyrano[3,2-c]chromen-5(4H)-ones and 7,7-dimethyl-7,8-dihydro-4H-chromen-5(6H)-ones from N,3-diaryl-3-oxo-propanethioamide, aromatic aldehyde, and 4-hydroxycoumarine or dimedone under mild reaction conditions. A plausible reaction mechanism is proposed. The 4H-pyrano[3,2-c]chromen-5-one and 7,7-dimethyl-7,8-dihydro-4H-chromen-5(6H)-one derivatives possessing 3-(2-chlorobenzoyl)-2-phenylamino-substituents further cyclized under basic conditions to yield penta-cyclic 7,13-diaryl-5,14-dioxa-13-aza-benzo[a]naphthacen-6,8(7H,13H)-dione and tetra-cyclic 6,12-diaryl-3,3-dimethyl-3,4-dihydro-2H-chromeno[2,3-b]quinolin-1,11(6H,12H)-dione, respectively.

MCPBA-Promoted Tandem Michael Addition–Intramolecular Cyclization of 2-Azido-β-amino Esters: Single Pot, Convenient Access to 1,2,4,5-Tetrasubstituted Imidazoles

A simple, single-pot synthesis of tetrasubstituted imidazoles has been developed through the use of MCPBA-promoted tandem Michael addition–intramolecular cyclization of 2-azido-β-amino esters.

Application of N,3-diaryl-3-oxo-propanethioamide in synthesis: an efficient and mild domino approach to highly substituted fused chromenones

A convenient and rapid synthesis of hitherto unknown 3-aroyl-4-aryl-2-phenylamino-4H-benzo[g]chromene-5,10-diones in high yield from β-aroyl-thioacetanilide, aromatic aldehyde, and 2-hydroxy-1,4-naphthoquinone via InCl3 catalyzed one-pot three-component tandem Knoevenagel condensation–Michael addition–intramolecular cyclization–elimination reaction sequence is disclosed for the first time. This domino protocol has been used to obtain highly substituted pyrano[3,2-c]chromen-5(4H)-ones and 7,7-dimethyl-7,8-dihydro-4H-chromen-5(6H)-ones from N,3-diaryl-3-oxo-propanethioamide, aromatic aldehyde, and 4-hydroxycoumarine or dimedone under mild reaction conditions. A plausible reaction mechanism is proposed. The 4H-pyrano[3,2-c]chromen-5-one and 7,7-dimethyl-7,8-dihydro-4H-chromen-5(6H)-one derivatives possessing 3-(2-chlorobenzoyl)-2-phenylamino-substituents further cyclized under basic conditions to yield penta-cyclic 7,13-diaryl-5,14-dioxa-13-aza-benzo[a]naphthacen-6,8(7H,13H)-dione and tetra-cyclic 6,12-diaryl-3,3-dimethyl-3,4-dihydro-2H-chromeno[2,3-b]quinolin-1,11(6H,12H)-dione, respectively.

ChemInform Abstract: Synthesis of Functionalized 2‐Aryl‐4‐(indol‐3‐yl)‐4H‐chromenes via Iodine‐Catalyzed Domino Michael Addition—Intramolecular Cyclization Reaction.

An efficient synthesis of novel functionalized 2-aryl-4-(indol-3-yl)-4H-chromenes has been developed, in the presence of a catalytic amount of iodine, from easily available starting materials, 2-hydroxychalcone derivatives. Indole, substituted indoles and 7-azaindole are suitable for this transformation. The possible domino Michael addition–intramolecular cyclization reaction mechanism is proposed.

Atom-economical synthesis of the functionalized spirocyclic oxindole-butenolide via three-component [2 + 2 + 1] cycloaddition strategy

The intermolecular [2 + 2 + 1] multicomponent cycloadditions from readily available isocyanides, activated alkynes and isatins are disclosed. This reaction proceeds by way of a Michael addition–nucleophilic addition–intramolecular cyclization sequence, thus providing new access to spirocyclic oxindole-butenolide with exclusive stereoselectivity in an efficient and atom-economical manner. A broad range of isatins and isocyanides including sterically demanding ones are also found to be compatible with the present protocol, which offers an opportunity for the construction of a new compound library. This protocol also allows the insertion of carbon monoxide into organic molecules without the aid of transition metal catalyst after hydrolysis process. Moreover, the cycloaddition–hydrolysis process by step can be further developed into a practical and powerful one-pot strategy in good yields together with convenient experimental set-up, which adds to its attractiveness.

Synthesis of functionalized 2-aryl-4-(indol-3-yl)-4H-chromenes via iodine-catalyzed domino Michael addition–intramolecular cyclization reaction

An efficient synthesis of novel functionalized 2-aryl-4-(indol-3-yl)-4H-chromenes has been developed, in the presence of a catalytic amount of iodine, from easily available starting materials, 2-hydroxychalcone derivatives. Indole, substituted indoles and 7-azaindole are suitable for this transformation. The possible domino Michael addition-intramolecular cyclization reaction mechanism is proposed.

Diastereoselective enzymatic synthesis of highly substituted 3,4-dihydropyridin-2-ones via domino Knoevenagel condensation–Michael addition–intramolecular cyclization

A direct method to construct 3,4-dihydropyridin-2-ones by enzymatic condensation of aldehyde with cyanoacetamide and 1,3-dicarbonyl compounds was developed. One ring and four new bonds (two C–C, one C–N, one C C) were formed in one pot. And reaction conditions involving hydrolases, solvents, substrate molar ratios, and hydrolase loading were optimized. A series of new compounds based on the 3,4-dihydropyridin-2-one core were synthesized by the unprecedented three-component domino reaction.

Organocatalytic Conjugate Addition of Malononitrile to Conformationally Restricted Dienones

Organocatalytic conjugate addition of malononitrile to conformationally restricted dienones has been studied. A series of chiral primary and tertiary amine catalysts were screened. A piperidine-based thiourea-tertiary amine was found to be the efficient catalyst. Chiral pyran derivatives were obtained in excellent yields and enantioselectivities via a cascade conjugate addition-intramolecular cyclization pathway. The reaction is remarkably different for the corresponding reaction of conformationally flexible dienones.

An Improved Asymmetric Synthesis of Piperazic Acids: Retro-Reaction in the Chiral Oxazolidinone Controlled Di-Azo Addition Reaction in a Dipolar Aprotic Medium

The asymmetric addition intramolecular cyclization reaction to produce the piperazic acid precursor 3 was studied. A retroaddition of S -4-(phenylmethyl)oxazolidinyl-5-bromovalerimide to diazo-di-tert-butyl dicarboxylate in DMPU/THF was discovered. A process improvement based on the addition of catalytic tetra-butylammonium iodide to give 3 in 91% yield is reported.