One‐pot four component condensation for the synthesis of novel dispirooxindole pyrrolidine linked 1,2,3‐triazoles via stereo‐ and regioselective [3 + 2] cycloaddition reaction in PEG‐400

Abstract

A one‐pot four component condensation of isatin, sarcosine, 2‐[2‐oxo‐1‐(prop‐2‐ynyl)indolin‐3‐ylidene]malononitrile and aryl azides has been reported for the synthesis of novel dispirooxindole pyrrolidine linked 1,2,3‐triazole conjugates using Cu(I) as a catalyst in PEG‐400 by stereoselective [3 + 2] azide‐alkyne cycloaddition followed by [3 + 2] azomethine ylide and alkene cycloaddition. Structures have been confirmed by spectral and X‐ray studies. Crystal packing of 5a has also been reported. Rapid reaction, easy work‐up and high yields are the salient features of the present protocol.

Green and Sustainable Solvents in Chemical Processes

“…MCRs have been carried out in a range of unconventional solvents including PEG, water, ILs, and bioderived solvents. Combined with smart synthetic strategies such as click chemistry, 292 MCRs have the potential to streamline organic synthesis substantially. The onepot synthesis of thiazoloquinoline scaffolds is an excellent example of MCRs in PEG solvents.…”

Green synthesis of 1,4-disubstituted 1,2,3-triazoles: a sustainable approach

“…Khurana and co-workers have demonstrated a one-pot four-component condensation reaction of isatin, sarcosine, 2-[2-oxo-1-( prop-2-ynyl)indolin-3-ylidene]malononitrile and aryl azides for synthesizing dispirooxindole pyrrolidine linked 1,4-disubstituted 1,2,3-triazole conjugates by employing Cu(I) as a catalyst and PEG-400 as green solvent at 100 °C. This reaction involves [3 + 2] AAC followed by [3 + 2] azomethine ylide and alkene cycloaddition to produce high yields, 77 as represented in Table 2, entry (9). Furthermore, Bhardwaj and co-workers have successfully synthesized a series of molecular hybrids comprising pyrazole, pyridinone, and 1,2,3-triazoles through a one-pot four-component reaction.…”

Engaging Isatins in Multicomponent Reactions (MCRs) – Easy Access to Structural Diversity

“…Isatin derivatives, sarcosine, 2‐[2‐oxo‐1‐(prop‐2‐ynyl)indolin‐3‐ylidene]malononitrile and aryl azides with Cu(I) as catalyst in polyethylene glycol (PEG‐400) as reaction medium, at 100 °C (Scheme 26) gave interesting dispirooxindole pyrrolidine linked 1,2,3‐triazole derivatives. This one‐pot 4‐MCR approach involves two sequential [3+2] cycloaddition reactions: stereoselective azide‐alkyne cycloaddition, azomethine ylide and alkene cycloaddition, affording the novel structurally diverse triazole containing dispirooxindole pyrrolidine heterocycles in good yields [54] …”

“…Dinuclear Zn [45] CuI/DBU [51] CuSO 4 .5H 2 O [54] , [55] , [59] chiral guanidine/CuI [191] Ag(I)‐NHC complex [174] …”

“…The versatility of this solvent was explored in the four component synthesis of bis‐oxindole derivatives, through a stereoselective copper‐catalyzed [3+2] azide‐alkyne cycloaddition followed by the already described [3+2] azomethine ylide and alkene cycloaddition, affording a small‐library of pyrrolidinyl dispirooxindole linked 1,2,3‐triazole derivatives (15 examples) (Scheme 106). [54] …”