Enantioselective synthesis of functionalized fluorinated dihydropyrano [2,3-c]pyrazoles catalyzed by a simple hi functional diaminocyclohexane-thiourea

Enantioselective synthesis of functionalized fluorinated dihydropyrano[2,3-c]pyrazoles has been achieved via a diaminocyclohexane-thiourea catalyzed cascade Michael addition and Thorpe-Ziegler type cyclization in high yields （up to 98%） with moderate to good enantioselectivity （up to 90% ee）.     

Microwave-assisted organocatalytic multicomponent Knoevenagel/hetero Diels-Alder reaction for the synthesis of 2,3-dihydropyran[2,3-c]pyrazoles

A rapid protocol for the multicomponent microwave-assisted organocatalytic domino Knoevenagel/hetero Diels-Alder reaction (DKHDA) has been developed for the synthesis of 2,3-dihydropyran[2,3-c]pyrazoles. The reported procedure could be used for the fast generation of novel substituted 2,3-dihydropyran[2,3-c]pyrazoles with potential anti-tuberculosis activity.     

Enantioselective organocatalytic synthesis of the chiral chromenes by domino oxa-Michael-aldol reaction

The proline based chiral organocatalyst has been found to be an efficient catalyst for enantioselective domino oxa-Michael-aldol reaction. This catalytic system provided the synthesis of substituted 2-aryl-2H-chromenes-3-carbaldehyde in good to high yields (73%–97%) with excellent enantioselectivity (up to 97%) and reasonable reaction times. The atom economy, high yield and mild reaction conditions are some of the important features of this protocol.     

Tetrabutylammonium hydrogen sulfate mediated domino reaction: synthesis of novel benzopyran-annulated pyrano[2,3-c]pyrazoles

A tetrabutylammonium hydrogen sulfate (TBA-HS) mediated procedure for one pot synthesis of novel benzopyran-annulated pyrano[2,3-c]pyrazoles via domino/Knoevenagel-hetero-Diels-Alder reaction has been demonstrated.     

Convenient synthesis of spiro[indoline-3,4'-pyrano[2,3-c]pyrazole] and spiro[acenaphthyl-3,4'-pyrano[2,3-c]pyrazoles] via fourcomponent reaction

The base promoted four-component reaction of hydrated hydrazine, dimethyl acetylenedicarboxylate, isatines and malononitrile (ethyl cycanoacetate) in ethanol afforded polysubstituted spiro[indoline-3,4‘-pyrano[2,3-c]pyrazoles] and spiro[acenaphthyl-3,4-pyrano[2,3-c]pyrazoles]     

Asymmetric organocatalytic anthrone additions to activated alkenes

Asymmetric organocatalytic additions of anthrones to activated alkenes are discussed. The reaction between anthrone or dithranol and α,β-unsaturated aldehydes is catalyzed by diphenylprolinol trimethylsilyl ether in toluene at −40 °C, giving the Michael adducts with good yields and enantioselectivities. Bifunctional amino-thioureas efficiently catalyze the additions of anthrones to both nitroalkenes and maleimides, and high enantioselectivities can be achieved in both instances at room temperature. In the case of nitroalkenes, a Michael addition takes exclusively place. Anthrone generally gives Diels-Alder cycloadducts in the reaction with maleimides, while dithranol affords the Michael adducts. Transition state working models in which the bifunctional catalyst binds simultaneously to the alkene and to the anthrone enolate account for the stereochemical outcome of these additions.     

Asymmetric synthesis of trifluoromethyl substituted dihydropyrans via organocatalytic cascade Michael-hemiketalization reaction

Asymmetric conjugate addition of ethyl 4,4,4-trifluoroacetoacetate and other trifluoromethyl substituted nucleophiles to β,γ-unsaturated α-keto esters has been developed. The reaction efficiently provided dihydropyrans via cascade Michael-hemiketalization pathways. Quinine-derived thiourea was identified to be the best catalyst. A number of trifluoromethyl substituted dihydropyrans with three consecutive chiral centers were obtained in excellent yields, diastereoselectivities, and enantioselectivities. The product was readily transformed to the corresponding tetrahydropyridine without the loss of the optical purity.     

Enantioselective organocatalytic aza-ene-type domino reaction leading to 1,4-dihydropyridines

A new general methodology was developed to access highly enantiomerically enriched 1,4-dihydropyridines (DHPs) 3 via an organocatalytic asymmetric aza-ene-type cascade reaction, cocatalyzed by (S)-diarylprolinol-TMS ether V and benzoic acid (BA). Both aliphatic and aryl enals 1 reacted smoothly with enaminones and β-enamino esters 2, affording highly functionalized 1,4-DHPs 3 in high enantioselectivities and good yields.     

Enantioselective organocatalytic Mannich reactions of ferrocenecarbaldehyde

The first examples of highly enantioselective organocatalytic Mannich reactions of ferrocenecarbaldehyde are disclosed. The reaction is catalyzed by simple amino acids and gives access to β-arylamino-β-ferrocenylketones in high yields and with up to 99% ee.     

Cesium carbonate supported on hydroxyapatite coated Ni0.5Zn0.5Fe2O4 magnetic nanoparticles as an effi cient and green catalyst for the synthesis of pyrano[2,3-c]pyrazoles

Cesium carbonate supported on hydroxyapatite coated Ni0.5Zn0.5Fe2O4 magnetic nanoparticles (Ni0.5Zn0.5Fe2O4@Hap-Cs2CO3) was found to be magnetically separable, highly efficient, green and recyclable heterogeneous catalyst. The synthesized nanocatalyst has been characterized with several methods (FT-IR, SEM, TEM, XRD and XRF) and these analyzes confirmed which the cesium carbonate is well supported to catalyst surface. After full characterization, its catalytic activity was investigated in the synthesis of pyranopyrazole derivatives and the reactions were carried out at room temperature in 50:50 water/ethanol with excellent yields (88-95%). More importantly, the Ni0.5Zn0.5Fe2O4@Hap-Cs2CO3 was easily separated from the reaction mixture by external magnetic field and efficiently reused at least six runs without any loss of its catalytic activity. Thus, the developed nanomagnetic base catalyst is potentially useful for the green and economic production of organic compounds.     

Synthesis of pyrano[2,3-c]pyrazoles: A review

One-pot synthesis of pyrano[2,3-c]pyrazole derivatives via two or multicomponent condensation of β-ketoesters, hydrazine monohydrate/phenyl hydrazine, malononitrile, and substituted benzaldehydes is of great interest not only in synthetic chemistry but also in medicinal chemistry because of the tremendous biological activities, such as anticancer, anti-inflammatory, analgesic, antimicrobial, and enzyme inhibitory activities exhibited by pyranopyrazoles. This review provides extensive knowledge on novel synthetic methodologies of biologically active non-spiro/spiro-pyrano[2,3-c]pyrazole derivatives published recently.     

Asymmetric synthesis of multi-substituted spiro[5,5]undecane-1,5,9-triones via organocatalytic three-component reaction

The asymmetric domino three-component Knoevanagel-Diels-Alder addition (ATCDA) reaction, as an important methodology, has been utilized to construct complex product from ordinary starting materials. In this report, many typical organoamine catalysts were investigated to achieve highly efficient asymmetric three-component reaction of enones 2, aldehydes 3 and Meldrum’s acid 4. Various pharmacological multi-substituted spiro[5,5]undecane-1,5,9-triones promoted by 9-amino-9-deoxy-epi-quinine 1 g in one-pot, were obtained in moderate to good yields (up to 81%) with excellent diastereo-(>99:1 dr) and enantioselectivities (up to 97% ee). Meanwhile, based on the controlled experiments and analytical data, a reasonable mechanism of dual-activity for this reaction has been proposed.     

Synthesis of the diarylindolizidine alkaloid (+)-Fistulopsine B: Application of an organocatalytic Michael addition reaction

The first synthesis of a recently isolated antiproliferative diarylindolizidine alkaloid, (+)-fistulopsine B, was achieved. The synthesis features the use of an organocatalytic ketone-nitrostyrene Michael addition as the key step.     

A general asymmetric route to enantio-enriched isoflavanes via an organocatalytic annulation of o-quinone methides and aldehydes

Reported herein is a general approach to optically active isoflavanes based on a chiral amine-catalyzed [4?+?2] asymmetric annulation of o-quinone methides and aldehydes. A number of naturally occurring isoflavanes, including equol, sativan, isosativan, vestitol and medicarpin, as well as isoflavane analogues were readily prepared with good to excellent enantioselectivities.     

Highly diastereo- and enantioselective construction of phthalide-oxindole hybrids bearing vicinal quaternary chiral centers via an organocatalytic allylic alkylation

A diastereo- and enantioselective synthesis of phthalide-oxindole hybrids including congested adjacent quaternary chiral centers was demonstrated through a Lewis base catalyzed asymmetric allylic alkylation reaction of Morita–Baylis–Hillman carbonates of isatins and 3-cyanophthalides. The various hybrid molecules with two valuable pharmacophores-combined frameworks can be obtained in good to high diastereo- and enantioselectivities.     

Asymmetric synthesis of tetrahydropyran[3,2-c]quinolinones via an organocatalyzed formal[3 + 3] annulation of quinolinones and MBH 2-naphthoates of nitroolefin

An efficient asymmetric and enantio-swithchable organocatalytic[3+3]annulation reaction using MBH-2-naphthoates of nitroalkenes and 4-hydroxyquinolin-2(1H)-ones has been developed.Densely substituted tetrahydropyrano[3,2-c]qui noli nones scaffolds with two adjacent stereogenic centers are obtained with high yield(up to 95%yield)and good stereoselectivities(up to>20:1 dr and 96%ee)in an enantio-switchable manner.Furthermore,gram scale synthesis was achieved and the nitro group could easily transform into an amino group without any appreciable loss in the diastereo-and enantioselectivity.     

Enantioselective organocatalytic aldol reaction of unactivated ketones with isatins

Enantioselective organocatalytic direct aldol reaction of unactivated ketones with various isatin derivatives was developed using cinchonine based urea ligand employing a noncovalent catalysis mechanism. Using this protocol we can access functionalized 3-alkyl-3-hydroxyindolin-2-ones in high yields with good to excellent enantioselectivities.     

Sonogashira Coupling Offers a New Synthetic Route to Thieno[2,3-c]pyrazoles

Abstract

1,3-Disubstituted-5-chloro-4-iodopyrazoles are selectively coupled with phenylacetylene under typical Sonogashira reaction conditions [PdCl₂(PPh₃)₂, CuI, Et₃N, dimethylformamide (DMF)] to obtain the corresponding 5-chloro-4-(phenylethynyl)pyrazoles in good yield. The latter are smoothly cyclized with Na₂S in DMF into the corresponding thieno[2,3-c]pyrazoles. Detailed spectroscopic investigations (¹H, ¹³C, and ¹⁵N NMR, mass, and infrared) of all compounds are reported.     

Enantioselective 1,6-Michael addition of anthrone to 3-methyl-4-nitro-5-alkenyl-isoxazoles catalyzed by bifunctional thiourea-tertiary amines

A simple and efficient method for the enantioselective 1,6-Michael addition reaction of anthrone to a series of 3-methyl-4-nitro-5-alkenyl-isoxazoles with a bifunctional thiourea-tertiary amine as catalyst is described. This transformation proceeds smoothly with 10 mol % catalyst and provides a series of Michael adducts bearing 3-methyl-4-nitro-isoxazole and anthrone units with good to high enantioselectivities (up to 96% ee) and in very high yields (up to 99%).