Spiropyrazoline synthesis via intramolecular cyclization/methylation

ORGN 347

Sureshbabu Dadiboyena, sureshsai5@yahoo.com and Ashton T. Hamme II, ashton.t.hamme@ccaix.jsums.edu. Department of Chemistry, Jackson State University, 1400 J.R. Lynch St., Jackson, MS 39217-0510
In recent years, 1,3-dipolar cycloaddition reaction has been applied as a useful methodology for the synthesis of various heterocycles. The synthesis of pyrazoline derivatives has received much attention due to their potential to exhibit various biological activities viz., anti-inflammatory, analgetics, herbicidal, virucidal, and insecticidal activity. Nitrile imines are a class of 1,3-dipoles which offer a vast scope in the synthesis of 5-membered pyrazoles and many methods for pyrazole synthesis have been developed. The readily synthesized highly funtionalized alkene, when subjected to [2+3]-dipolar cycloaddition reaction with in situ generated aromatic nitrile imines, affored the corresponding desired 5,5-disubstituted pyrazoline cycloadduct as a single regioisomer. Subsequent intramolecular cyclization/methylation carried out in one pot by employing suitable bases afforded the regiomeric mixture of spiropyrazolines, which resulted from the O-alkylation of both spiropyrazoline intermediate enolates. Our interests in this area include approaches to the syntheses of various potentially biologically active spiropyrazoline molecules that may have applications in breast cancer.