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Stereoselective Synthesis of 1-Substituted Homotropanones, including Natural Alkaloid (-)-Adaline
Sandra Hernández-Ibáñez1,2,3, Ana Sirvent1,2,3, Miguel Yus3
1Departamento de Química Orgánica, Facultad de Ciencias, Universidad de Alicante, Apdo. 99, 03080 Alicante, Spain.
Abstract:
The stereocontrolled synthesis of 1-substituted homotropanones, using chiral N-tert-butanesulfinyl imines as reaction intermediates, is described. The reaction of organolithium and Grignard reagents with hydroxy Weinreb amides, chemoselective N-tert-butanesulfinyl aldimine formation from keto aldehydes, decarboxylative Mannich reaction with β-keto acids of these aldimines, and organocatalyzed L-proline intramolecular Mannich cyclization are key steps of this methodology. The utility of the method was demonstrated with a synthesis of the natural product (-)-adaline, and its enantiomer, (+)-adaline.
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