A catalytic system‐controlled divergent reaction strategy was here reported to construct four types of intriguing spiroheterocyclic skeletons from simple and readily available starting materials via ...a precise chemical bond activation/n+1 annulation cascade. The tetraazaspiroheterocyclic and trizazspiroheterocyclic scaffolds could be independently constructed by a selective N−N bond activation/n+1 annulation cascade, a C(sp2)‐H activation/4+1 annulation and a novel tandem C(sp2)‐H/C(sp3)−H bond activation/4+1 annulation strategy, along with a broad scope of substrates, moderate to excellent yields and valuable transformations. More importantly, in these transformations, we are the first time to capture a N−N bond activation and a C(sp3)−H bond activation of pyrazolidinones under different catalytic system.
Four types of novel and complicated spiropyrazolones from pyrazolidinones and diazopyrazolones were constructed via a precise chemical bond activation/n+1 annulation route, especially a selective N−N bond activation/n+1 annulation cascade and a novel tandem C(sp2)−H/C(sp3)−H bond activation/4+1 annulation strategy, and diazopyrazolones acted as unexpected 1C synthons.
The regio‐ and stereoselective 1,3‐dipolar reaction is an important tool to build five‐membered heterocycles. Fluoroalkylated α,β‐unsaturated building blocks were used in the 1,3‐dipolar reaction of ...nitrones and azomethine imines without any catalysts and additives to obtain fluorinated pyrazolidinones and isoxazolidines. High endo‐selectivity for nitrones and exo‐selectivity for azomethine imines were observed, and supported by DFT calculations of Gibbs free energy changes in CH3CN. More information can be found in the Full Paper by Yi‐Yong Huang et al. on page 1830 in Issue 9, 2018 (DOI: 10.1002/ajoc.201800435).
Display omitted
•Rh-catalyzed 4+1 annulation afforded pyrazolo1,2-a indazole derivatives.•Reaction occurred under mild conditions and have good functional group tolerance.•KIE experiments were ...conducted to explore the possible mechanism.
A Rhodium(III)-catalyzed 4+1 annulation and ring opening of 1‑alkynylcyclobutanols with pyrazolidinones to access pyrazolo1,2-a indazoles bearing a quaternary carbon center was described. This method features high functional group tolerability and afforded pyrazolo1,2-a indazoles in moderate to good yield under mild conditions.
N-arylated α-amino acids and pyrazolidin-3-ones are widely being used as chiral building blocks for pharmaceuticals and agrochemicals. Here we report a biocatalytic route for the asymmetric synthesis ...of various N-arylated aspartic acids applying ethylenediamine-N,N′-disuccinic acid lyase (EDDS lyase) as a biocatalyst. This enzyme shows a broad substrate scope, enabling the addition of a variety of arylamines to fumarate with high conversions, yielding the corresponding N-arylated aspartic acids in good isolated yields and with high enantiomeric excess (ee > 99%). Furthermore, we developed a chemoenzymatic method toward the synthetically challenging chiral 2-aryl-5-carboxylpyrazolidin-3-ones, using arylhydrazines as bis-nucleophilic donors in the EDDS lyase catalyzed hydroamination of fumarate followed by an acid-catalyzed intramolecular amidation, achieving good overall yields and high optical purity (ee > 99%). In addition, we successfully combined the EDDS lyase catalyzed hydroamination and acid-catalyzed cyclization steps in one pot, thus providing a simple chemoenzymatic cascade route for synthesis of enantiomerically pure pyrazolidin-3-ones. Hence, these biocatalytic methods provide convenient alternative routes to important chiral N-arylated aspartic acids and difficult 2-aryl-5-carboxylpyrazolidin-3-ones.
Display omitted
Recyclization of N-arylitaconimides with hydrazine in dioxane at room temperature selectively leads to 2-(3-oxopyrazolidin- 4-yl)acetanilide derivatives in moderate to good yields. ...The similar reaction with phenylhydrazine proceeds with the simultaneous formation of isomeric 3- and 5-oxo- 1-phenylpyrazolidine-containing acetanilides.
Display omitted
•A metal and catalyst free 1,3-dipolar cycloaddition has been developed.•Gram-scale reaction could be achieved.•Fully substituted pyrazole can be obtained by easy transformation.
A ...metal and catalyst free 1,3-dipolar cycloaddition reaction of azomethine imines with internal alkynes has been developed. Various N,N-bicyclic pyrazolidinones could be prepared quickly under microwave irradiation in moderate to excellent yields (up to 96%). A wide range of azomethine imines and electron-deficient internal alkynes were applicable to this reaction. In addition, gram-scale reaction could be achieved and fully substituted pyrazole can be obtained by easy transformation of N,N-bicyclic pyrazolidinone. This environment friendly dipolar cycloaddition is remarkable for its simplicity in conditions and wide structural diversity.
Display omitted
•Novel 3D-rich scaffold among PfDHODH inhibitors.•Simple synthetic method, broad scope, separable diastereomers.•Separable diastereomers, tunable substitution pattern.•Inhibition of ...PfDHODH at low µM concentration.•High selectivity of inhibition, PfDHODH vs. HsDHODH.
The reactions between 5-substituted pyrazolidine-3-ones, aldehydes, and methyl methacrylate provided tetrahydropyrazolo1,2-apyrazole-1-carboxylates as mixtures of syn- and anti-diastereomers. Testing for inhibition of dihydroorotate dehydrogenase of Plasmodium falciparum (PfDHODH) revealed high activity of some anti-isomers of the methyl esters, while the corresponding carboxylic acids and carboxamides were not active. The most active representative, methyl (1S*,3S*,5R*)-1,5-dimethyl-7-oxo-3-phenyltetrahydro-1H,5H-pyrazolo1,2-apyrazole-1-carboxylate (IC50 = 2.9 ± 0.3 μM), also exhibited very high selectivity of the parasite enzyme vs. the human enzyme, PfDHODH/HsDHODH > 350. According to the molecular docking score, this high activity is explainable by synergic interactions of the methyl, phenyl and the CO2Me substituent with the hydrophobic pockets in the active site of the enzyme. The carboxylic acid and carboxamides derived from this compound did not inhibit PfDHODH.
The first asymmetric N‐allylic alkylation of hydrazones with Morita‐Baylis–Hillman (MBH) carbonates catalyzed by modified Cinchona alkaloids has been developed, affording N‐substituted hydrazones in ...good yields with exclusive regioselectivities and excellent enantioselectivities. Subsequent transformations of the allylic alkylation products led to synthetically useful pyrazolidinones.
A highly atom‐economic, regio‐ and stereospecific synthesis of fluorinated pyrazolidinones and isoxazolidines is disclosed under catalyst‐ and additive‐free mild conditions. The diastereoselectivity ...with different type of 1,3‐dipoles is elucidated by using DFT calculations in CH3CN. Furthermore, a reaction using a chiral azomethine imine, a gram‐scale synthesis, and a reductive desulfonylation are also presented.
One way or another: A high‐yielding, diastereoselective 1,3‐dipolar cycloaddition of β‐fluoroalkylated unsaturated building blocks providing access to fluoroalkylated heterocycles of pyrazolidinones and isoxazolidines under catalyst‐free conditions is described. The diastereoselective process was supported by DFT calculations.
PDF
![Rh(III)-catalyzed [4+1] ann...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/0040-4039/small "Rh(III)-catalyzed [4+1] annulation and ring opening for the synthesis of pyrazolo[1,2-a] indazole bearing a quaternary carbon")
