Enantioselective Construction of CF₃-Containing Spirooxindole γ-Lactones via Organocatalytic Asymmetric Michael/Lactonization

Abstract

A highly enantioselective Michael/lactonization cascade reaction of 3-hydroxyoxindoles with 3-trifluoroethylidene oxindoles was developed. The use of a cinchona-derived squaramide catalyst is essential in achieving high diastereo- and enantioselectivities. This reaction represents the first example of intramolecular amide C–N bond cleavage and lactonization of 3-hydroxyoxindoles with 3-trifluoroethylidene oxindoles, which provides an efficient and convenient approach to diverse CF3-containing spirooxindole γ-lactones in high yields and good to excellent diastereo- and enantioselectivities.

Recent Advances in the Construction of Trifluoromethyl‐Containing Spirooxindoles through Cycloaddition Reactions

“…An intramolecular lactonization reaction occurred and created the final product (Scheme 11,b). [22] α-Trifluoromethyl-alkylidene oxindole is another kind of isatin derivatives containing a trifluoromethyl group. In 2018, Moreau's group described a Fe-catalyzed [4 + 2] cycloaddition reaction of α-trifluoromethyl-alkylidene oxindoles and 4-phenylhexa-2,4-dienal derivatives.…”

“…The plausible reaction mechanism suggested that an enantioselective Michael reaction firstly happened, and produced the adduct intermediate. An intramolecular lactonization reaction occurred and created the final product (Scheme , b) …”

Natural and Synthetic Spirobutenolides and Spirobutyrolactones

“…Recently, Deng and coworkers reported a stereoselective Michael/lactonization tandem reaction of 3-trifluoroethylidene oxindoles and 3-hydroxyoxindoles using a cinchona-derived squaramide catalyst (Scheme 42). [92] Under mild conditions, chemically inert amides of oxindoles were converted into the spirolactones. Various CF 3 -substituted spirolactones were synthesized in moderate to excellent yields (up to 97%), enantioand diastereoselectivities (up to 98% ee and 98 : 2 dr).…”

“…Recently, Deng and coworkers reported a stereoselective Michael/lactonization tandem reaction of 3‐trifluoroethylidene oxindoles and 3‐hydroxyoxindoles using a cinchona‐derived squaramide catalyst (Scheme ) . Under mild conditions, chemically inert amides of oxindoles were converted into the spirolactones.…”

Dynamic stereoselective annulation via aldol-oxa-cyclization cascade reaction to afford spirooxindole pyran polycycles

“…Whereas syntheses of many classes of spirooxindole polycycles bearing Nheterocycles and spirooxindole all-carbon polycycles have been reported [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] , few examples of the syntheses of spirooxindole polycycles bearing O-heterocycles have been reported 22,23 . Most methods developed for the synthesis of the spirooxindole O-heterocycles provide nonpolycyclic derivatives [24][25][26][27][28][29][30][31][32][33] . Because the lengths of C-C, C-N, and C-O bonds are different, spirooxindole polycyclic scaffolds bearing oxygen-containing heterocycles should provide molecules with biological functions different from those of spirooxindole all-carbon polycyclic and N-heterocycle-containing polycyclic systems.…”