3-(2-Azidoethyl)oxindoles: Advanced Building Blocks for One-Pot Assembly of Spiro[pyrrolidine-3,3′-oxindoles]

Abstract

A new synthetic approach to biologically relevant spiro[pyrrolidine-3,3'-oxindoles] was developed on the basis of the cascade transformation of 3-(2-azidoethyl)oxindoles via Staudinger/aza-Wittig/Mannich reactions. The parent azides were readily synthesized through a nucleophilic ring opening of spiro[cyclopropane-1,3'-oxindoles] with the azide ion. A series of new spiro[pyrrolidine-3,3'-oxindoles] with various (het)aryl substituents at the C2 and C5 positions of the pyrrolidine ring were synthesized. In vitro experiments revealed their high cytotoxicity toward LNCaP and PC-3 tumor cell lines.

Stereoselective synthesis and applications of spirocyclic oxindoles

“…197 Budynina has performed a similar ring expansion in a sequential azide anion ring opening followed by a Staudinger/ Wittig/Mannich reaction. 198 Whereas Hajra has ring expanded 3-spiroaziridinyl oxindoles using malonitrile (Scheme 41). 199 This type of ring expansion chemistry has also been carried out in an inverse fashion, i.e.…”

Recent Advances in the Synthesis of Heterocycles by the Aza-Wittig Reaction

“…In 2017, Budynina and co-workers reported the one-pot synthesis of spiro[pyrrolidine-3,3′-oxindoles] 244 (Schemes 62 and 63). 57 The route begins with the synthesis of intermediate cyclopropanes 240 through the Knoevenagel condensation and Corey-Chaykovsky reactions. Cyclopropanes 240 underwent nucleophilic ring-opening reaction with sodium azide under microwave irradiation to give azides 241 with notable regioselectivity (Scheme 62).…”

Syntheses and Applications of Spirocyclopropyl Oxindoles: A Decade Review

“…Compound 156a revealed excellent cytotoxic profile against LNCaP cancer cells with IC 50 value of 2.0 ± 1.2 µ m (Scheme 46). [ 64 ] Interestingly, the Studinger reaction of the 3‐oxindole‐substituted ethyl azides 153 with Ph 3 P generated phosphazene intermediates 154 , which upon reaction with acrolein 157 engendered spiro[azepane‐4,3'‐oxindoles] 159 (Scheme 47). [ 65 ]…”