Multicomponent Reaction Discovery: Three-Component Synthesis of Spirooxindoles

Abstract

The Lewis acid catalyzed, three-component reaction of isatin and two 1,3-dicarbonyl compounds is reported. Reactions proceed with high efficiency under mild reaction conditions and with good functional group tolerance to afford spirooxindole pyranochromenedione derivatives.

Recent Progress on Routes to Spirooxindole Systems Derived from Isatin

“…With different Michael donors, diversely fused heterocycles with pyran or 1,4‐dihydropyridine moiety will be established. For example, the listed donors such as 3‐methyl‐1 H ‐pyrazol‐5(4 H )‐one , 4‐hydroxycoumarin , 4‐hydroxyquinolin‐2(1H)‐one and its N ‐allylic derivatives , cyclic 1,1‐enediamine , dimedone , 1‐(2‐phenylhydrazono)propan‐2‐one , β‐diketone or β‐ketoester , 2‐hydroxynaphthalene‐1,4‐dione , 3‐aminophenol , 2‐methyl pyrimidine‐4,6‐diol , 3‐methyl‐1 H ‐pyrazol‐5‐amine , naphthalen‐2‐amine , 1 H ‐indene‐1,3(2 H )‐dione , naphthalen‐2‐ol , and furan‐2,4(3 H ,5 H )‐dione are proved to be efficient for such protocol. Certainly, the suitable electron‐rich donors for such domino reaction are not limited to the aforementioned ones, and they can be reasonably extended to others with their functional group diversity.…”

Highly stereoselective construction of novel dispirooxindole–imidazolidines via self-1,3-dipolar cyclization of ketimines

“…Interestingly, the amount of 3,5-DNBA severely affected the chemical yield. Lower (0.2 equiv) or large amount (5 equiv) of 3,5-DNBA dramatically decreased chemical yields (entries [13][14][15]. It is worth noting that a slow decomposition of cycloadduct on silica gel column was observed and a slightly higher yield was achieved via purification on neutral aluminum oxide column (comparison of entry 14 and entry 16).…”

Regio- and stereoselective syntheses and cycloadditions of substituted 2H-pyran-2-ones and their fused derivatives

“…45 Stephenson and co-workers have investigated many possible Lewis acids (including TiCl 4 , BF 3 ·OEt 2 and SnCl 4 , the last being found to be the most efficient) and various conditions (including conventional heating in 1,2-dichloroethane at 60 °C or with microwave irradiation at 80 °C in the same solvent). The most appropriate were found to be the microwave conditions enabling the decrease of the necessary reaction times from 12-20 h to just 80 min and in most cases providing the products 70 with increased yields.…”