Highly Diastereoselective Vinylogous Mukaiyama Aldol Reaction of Isatins with 2-(Trimethylsilyloxy)furans Catalyzed by Quinine

Abstract

The diastereoselective formation of δ-hydroxyalkyl butenolide oxindoles has been achieved via a vinylogous Mukaiyama aldol reaction. The reaction was performed using various (N-alkyl)isatins 1 with 2-(trimethylsilyloxy)furan 2 catalyzed by quinine in tetrahydrofuran (THF). The reaction proceeds rapidly and affords the corresponding 3-hydroxy-(5-oxo-2,5-dihydrofuran-2-yl)indolin-2-ones in good yields with high diastereoselectivities (anti/syn ratio up to 96:4).

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GRAPHICAL ABSTRACT

Keywords:

• Diastereoselective synthesis
• 3-hydroxyoxindole
• isatins
• quinine
• vinylogous Mukaiyama aldol reaction

Notes

^a Unless otherwise specified, all reactions were carried out using isatin 1a (0.5 mmol, 1 equiv) and TMSOF 2 (1.0 mmol, 2 equiv) in 3 mL solvent with 10 mol% of catalyst at −78 °C.

^b Yield of isolated product of 3a after column chromatography.

^c Determined by ¹H NMR of crude product 3a.

^d The reaction was performed at −50 °C.

^e The reaction was performed at −20 °C.

^a Reaction conditions: isatin 1 (0.5 mmol), TMSOF 2 (1.0 mmol), in 3 mL of THF at −78 °C in the presence of 10 mol% of catalyst 4 h for 15 min.

^b Isolated yield after silica-gel chromatography of 3.

^c Determined by ¹H NMR of crude product 3.