Asymmetric Organocatalytic Synthesis of Highly Functionalized Spirocyclohexane Indandiones via a One-Pot Michael/Michael/Aldol Sequence

Abstract

The asymmetric organocatalytic one-pot Michael/Michael/ aldol reaction of trifluoromethyl-substituted 1,3-dicarbonyl compounds, nitroolefins, and 2-arylidene indandiones catalyzed sequentially by a cinchona-derived squaramide and DBU leads to spirocyclohexane-indan-1,3-diones bearing five adjacent stereogenic centers including a trifluoromethylated one in medium to very good yields and enantioselectivities, but generally in low to high diastereomeric ratios.

Key words

organocatalysis - one-pot reaction - squaramide - trifluoromethyl group - spirocycles

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• 11 The enantiomeric excess of the Michael adduct 3a could not be determined by chiral stationary phase HPLC or SFC, but was estimated by NMR measurement with a chiral shift reagent to be approximately 60%.
• 12 A complete list of tested substrates can be found in the Supporting Information.
• 13a CCDC 1406112 (major diastereomer of 5b) and CCDC 1406111 (minor diastereomer of 5b) contain the supplementary crystallographic data for this paper. The crystallographic data of both diastereomers of compound 5b are available free of charge at http://www.ccdc.cam.ac.
• 13b The unit cell of the major diastereomer of 5b includes an additional molecule of the same absolute configuration. For clarity only one molecule is depicted. Furthermore, the crystal structure of both diastereomers included one benzene molecule as solvent, which is also not depicted. Further details can be found in the Supporting Information.
• 13c The proposed mechanism and a model for the stereoselectivity can be found in the Supporting Information.