Issue 40, 2021

Oxazaborolidine-catalyzed reductive parallel kinetic resolution of ketones from β-nitro-azabicycles for the synthesis of chiral hypoestestatins 1, 2

Abstract

A novel approach for the synthesis of 13a-methyl tylophora alkaloids has been reported. The key features included two different synthetic pathways targeted at transforming the β-nitro-azabicycle to the phenanthrene core. The successful steps involved the oxidation of the nitro-piperidine moiety to the corresponding α,β-unsaturated ketone, and an oxidative biaryl coupling reaction for phenanthrene ring formation. Finally, the desired product was obtained via a formal reductive removal of the hydroxyl group. This methodology has been applied for the synthesis of 13a-methyl tylophora alkaloids in up to 65% yield over six steps from β-nitro-azabicycles. Both natural and unnatural enantioenriched hypoestestatins 1 and 2, and related compounds were synthesized using parallel kinetic resolution of the CBS-oxazaborolidine-catalyzed reduction of racemic ketones to provide two separable diastereomeric alcohols in combined yields up to 91% and with high enantioselectvity (up to 89% ee). In addition, the catalytic asymmetric reduction to seco-hypoestestatins 1 and 2 has been reported for the first time. Thus, the ability to develop the racemic mixtures to both enatioenriched forms offers benefit for various biological assays in the future.

Graphical abstract: Oxazaborolidine-catalyzed reductive parallel kinetic resolution of ketones from β-nitro-azabicycles for the synthesis of chiral hypoestestatins 1, 2

Supplementary files

Article information

Article type
Paper
Submitted
16 Aug 2021
Accepted
24 Sep 2021
First published
24 Sep 2021

Org. Biomol. Chem., 2021,19, 8794-8805

Oxazaborolidine-catalyzed reductive parallel kinetic resolution of ketones from β-nitro-azabicycles for the synthesis of chiral hypoestestatins 1, 2

W. Disadee and S. Ruchirawat, Org. Biomol. Chem., 2021, 19, 8794 DOI: 10.1039/D1OB01608C

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements