1,3-Dipolar cycloaddition of methyl 4-[2-(2-oxo-1,2-dihydro-3H-indol-3-ylidene)acetyl]phenylcarbamate to non-stabilized azomethine ylides generated by decarboxylation of α-amino acid (sarcosine and proline) adducts with ketones (isatin and ninhydrin) occurred regioselectively with formation of the corresponding spiro compounds having a carbamate moiety.In continuation of our studies on the synthesis of biologically active compounds having a carbamate functionality we examined three-component reactions with participation of methyl 4-[2-(2-oxo-1,2-dihydro-3H-indol-3-ylidene)acetyl]phenylcarbamate (I) which was prepared in turn by condensation of isatin with methyl (4-acetylphenyl)carbamate [1].3-[(E)-2-Oxo-2-arylethylidene]-2,3-dihydro-1H-indol-2-ones are dipolarophiles in which electronic and steric factors act in opposite directions; therefore, it is difficult to predict regioselectivity of 1,3-dipolar cycloadditions with participation of these compounds [2]. Analysis of electronic effects shows that electron density in their molecules is displaced toward the benzoyl fragment, whereas steric factor favors reaction at the opposite position of the exocyclic double bond.It is known that the structure of 1,3-dipolar cycloaddition products derived from heteroatom N-ylides and 3-[(E)-2-aryl(hetaryl)-2-oxoethylidene]-2,3-dihydro-1H-indol-2-ones [3] and from non-stabilized azomethine ylides and (E)-2-arylmethylidene(furfurylidene)-1,2,3,4-tetrahydronaphthalen-1-ones [4,5] is determined by both dipolarophile nature and reaction conditions. It was shown previously that 1,3-dipolar cycloaddition of azomethine ylides to (Z)-or (E)-oxoindolylideneacetophenones is stereospecific and that its regioselectivity depends on the reaction conditions [6]. According to the 1 H NMR and X-ray diffraction data [2], the regioselectivity in the cycloaddition of 3-[(E)-2-oxo-2-aryl(hetaryl)ethylidene]-2,3-dihydro-1H-indol-2-ones to azomethine ylides generated from L-proline and substituted isatins by heating in boiling aqueous propan-2-ol depends on the electronic nature of substituent in position 7 of isatin which acts as 1,3-dipole. Isatin having no substituent on C 7 gives rise to syn,endo-adducts, whereas syn,exo-addition products are obtained from 7-substituted derivatives (Cl, Me, Et).Synthesis of new functionalized pyrrolidine derivatives is important from the viewpoint of preparation of peptidomimetic library [7]. Spiro-fused pyrrolidines exhibit a broad spectrum of biological activity, in particular antimicrobial, antitumor, and antibacterial; they also inhibit human NK-1 receptors [8].In view of the above stated, it seemed important to involve new 3-[(E)-2-oxo-2-arylethylidene]-2,3-dihydro-1H-indol-2-ones, in particular those possessing a carbamate moiety, in 1,3-dipolar cycloaddition. It was also important to examine the regioselectivity of cycloaddition in three-component reactions with other N-substituted α-amino acids and carbonyl compounds.We found that 1,3-dipolar cycloaddition to carbamate I of azomethine ylides generated by...
