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. 2013 May 8;54(19):2311-2314.
doi: 10.1016/j.tetlet.2013.02.030.

Enantioselective Synthesis of Spiro[cyclohexane-1,3'-indolin]-2'-ones Containing Multiple Stereocenters via Organocatalytic Michael/Aldol Cascade Reactions

Arun K Ghosh  1 , Bing Zhou  1
Affiliations

Enantioselective Synthesis of Spiro[cyclohexane-1,3'-indolin]-2'-ones Containing Multiple Stereocenters via Organocatalytic Michael/Aldol Cascade Reactions

Arun K Ghosh et al. Tetrahedron Lett. .

Abstract

Organocatalytic reactions of 3-olefinic oxindoles and pentane-1,5-dial were investigated to provide access to substituted spirocyclohexane oxindoles via Michael/Aldol cascade reactions. Of particular interest, we have examined the stereochemical outcome of electron withdrawing and electron-donating groups on the oxindole ring nitrogen. Interestingly, we have observed that the N-protecting group on the oxindole has critical effect on aldol ring closure leading to ultimate stereochemical outcome of the hydroxyl center. The overall process is quite efficient and afforded products with multiple stereocenters in high yields and excellent enantioselectivities (>99% ee).

Keywords: Aldol reaction; Asymmetric catalysis; Michael reaction; Organocatalyst; Spiroindole.

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Figures

Figure 1
Figure 1
Structure and enantioselectivity of major isomer
Figure 2
Figure 2
ORTEP drawing of 5l and 7
Scheme 1
Scheme 1
Michael/aldol cascade with oxindole 1a and dialdehyde 2.
Scheme 2
Scheme 2
Reaction of oxindole 1a and 3-methylpentane-1,5-dial 6
Scheme 3
Scheme 3
Synthesis of benzoate 7
See this image and copyright information in PMC

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