Catalyst free three-component synthesis of (±)-pyrazolylpyrrolopyrroles by 1,3-dipolar cycloaddition reaction

Azomethine Ylides—Versatile Synthons for Pyrrolidinyl-Heterocyclic Compounds

“…Another reaction of maleimide 371 with pyrazole-4-carbaldehyde 382 and α -amino acid ester 383 , proceeding via azomethine intermediates in refluxing toluene, afforded the corresponding pyrazolylpyrrolopyrrole 384 ( Scheme 122 ) [ 162 ].…”

Highly Efficient and Diastereoselective Synthesis of New Pyrazolylpyrrolizine and Pyrazolylpyrrolidine Derivates by a Three-Component Domino Process

“…The reaction consists of a domino process as shown in Scheme 3. We propose that initially the condensation of the glycine derivative 3a with the formylpyrazole 1a produced the imine 7a ; subsequently, a 1,2-proton shift in imine 7a should afford the azomethine ylide 7b , which in turn should be trapped by the maleimide 2a to generate the intermediate pyrrolopyrrolidine derivative 8 (Scheme 3) [28].…”

“…On the other hand, it is known that a similar three-component reaction using α-amino acids can be stopped at the pyrazolyl-pyrrolo[3,4- c ]pyrroles 8 if the second cycloaddition is blocked by replacing the proton on the α-carbon atom by an alkyl group [28,29]. Thus, in order to preclude the formation of compounds type 4 , we performed the reaction with N -benzylglycine ethyl ester 3b instead of 3a , along with the formylpyrazoles 1a – b and maleimides 2a – e (Scheme 4).…”

“…Pyrazole is another five-membered ring with many applications in chemistry, especially as pharmaceuticals, pesticides and lubricants [23,24,25,26,27]. In connection with our current studies on the development of new, selective, and environmentally friendly methodologies for the synthesis of fused heterocycles [28,29,30,31], herein we report a procedure for the preparation of the scarcely studied pyrazolylpyrrolizine derivates 4 and pyrazolylpyrrolidine derivatives 5 and 6 where three moieties of known importance ( i.e ., pyrazole, pyrrolidine, pyrrolizine) are incorporated into a single structure. The new compounds were obtained in good yields and high diastereoselectivity by a catalyst-free three-component domino reaction between formylpyrazoles 1 , N -arylmaleimides 2 and glycine-derived esters 3 (Scheme 1).…”

Methyl (3aRS,3cRS,6cSR,7RS,8RS,8aSR)-2,5-bis(4-chlorophenyl)-7,9-bis(1,3-diphenyl-1H-pyrazol-4-yl)-1,3,4,6-tetraoxododecahydro-1H-dipyrrolo[3,4-a:3′,4′-f]pyrrolizine-3b-carboxylate dimethylformamide disolvate: a three-dimensional hydrogen-bonded framework

“…Multicomponent reactions are of great synthetic importance because of their simplicity, diversity and selectivity. Equally, 1,3-dipolar cycloaddition reactions between azomethinic ylides and electrodeficient alkenes are an important method for the synthesis of pyrrolidinic-type heterocyclic compounds (Zhang & Chen, 2005;Cui et al, 2011;Quiroga et al, 2011). We report here the structure of the title compound, (I), as a dimethylformamide disolvate, prepared as an example of a catalyst-free tricomponent reaction between formylpyrazoles, N-arylmaleimides and methyl glycinate (see Scheme 1) for the synthesis of a pyrazole-substituted dipyrrolo[3,4-a:3 0 ,4 0 -f]pyrrolizine, where three important heterocyclic units of known biological potential, namely pyrrole, pyrazole and pyrrolizidine, have been incorporated into this product of a doubleclick reaction (Radwan & El-Kashef, 1998;Ribes et al, 2009).…”