Universität zu Köln

Kim, Ji Hye (2015). Brønsted acid catalyzed asymmetric acetalizations. PhD thesis, Universität zu Köln.

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Abstract

This work describes the development of Brønsted acid catalyzed asymmetric acetalization of aldehydes and its application to kinetic resolution of chiral diols. In the first part, the first asymmetric version of the direct O,O-acetalization of aldehydes with 1,2- and 1,3-diols is presented. The reaction is catalyzed by chiral confined Brønsted acids, which are based on an imidodiphosphoric acid moiety and can provide structurally versatile confined chiral microenvironments. A new confined catalyst significantly outperformed previously established phosphoric acids and their derivatives, giving highly enantioenriched acetal products. The catalyst is readily prepared from the natural product thymol, possessing isopropyl and methyl substituents in the 2- and 5-position, respectively, on the aryl group providing a more rigid catalyst structure. A highly enantioselective reaction can be performed delivering acetals with excellent enantioselectivity (er up to 99.8:0.2) and excellent yields. The method tolerates both aliphatic and aromatic aldehydes delivering the corresponding acetal products with high enantioselectivities. The second part of this thesis describes a highly enantioselective kinetic resolution of chiral racemic diols through acetal formation employing the thymol derived imidodiphosphoric acid catalyst and an even bulkier catalyst which possesses a cyclohexyl substituent instead of the isopropyl substituent in the 2-position on the aryl group. The reaction is highly efficient for the resolution of diols with tertiary alcohol stereocenters, giving selectivity factors of up to 389. Remarkably, in cases where the selectivity factors are only moderate, highly enantioenriched diols can still be obtained via a stereodivergent resolution to diastereomeric acetals. This approach can be used for resolution of 1,2-diols possessing similar aliphatic substituents at the tertiary alcohol stereocenter. Initial studies regarding the development of related asymmetric S,O- and S,Sacetalizations are also presented in this thesis.