Issue 10, 2019

Metal-free alkene carbooxygenation following tandem intramolecular alkoxylation/Claisen rearrangement: stereocontrolled access to bridged [4.2.1] lactones

Abstract

Alkene carbooxygenation has attracted considerable attention over the past few decades as this approach provides an efficient access to various oxygen-containing molecules, especially the valuable O-heterocycles. However, examples of catalytic alkene carbooxygenation via a direct C–O cleavage are quite scarce, and the C–O cleavage in these cases is invariably initiated by transition metal-catalyzed oxidative addition. We report here a novel Brønsted acid-catalyzed intramolecular alkoxylation-initiated tandem sequence, which represents the first metal-free intramolecular alkoxylation/Claisen rearrangement. Significantly, an unprecedented Brønsted acid-catalyzed intramolecular alkene insertion into the C–O bond via a carbocation pathway was discovered. This method allows the stereocontrolled synthesis of valuable indole-fused bridged [4.2.1] lactones, providing ready access to biologically relevant scaffolds in a single synthetic step from an acyclic precursor. Moreover, such an asymmetric cascade cyclization has also been realized by employing a traceless chiral directing group. Control experiments favor the feasibility of a carbocation pathway for the process. In addition, biological tests showed that some of these newly synthesized indole-fused lactones exhibited their bioactivity as antitumor agents against different breast cancer cells, melanoma cells, and esophageal cancer cells.

Graphical abstract: Metal-free alkene carbooxygenation following tandem intramolecular alkoxylation/Claisen rearrangement: stereocontrolled access to bridged [4.2.1] lactones

Supplementary files

Article information

Article type
Edge Article
Submitted
06 jan 2019
Accepted
23 jan 2019
First published
24 jan 2019
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2019,10, 3123-3129

Metal-free alkene carbooxygenation following tandem intramolecular alkoxylation/Claisen rearrangement: stereocontrolled access to bridged [4.2.1] lactones

L. Li, X. Zhu, Y. Zhang, H. Bu, P. Yuan, J. Chen, J. Su, X. Deng and L. Ye, Chem. Sci., 2019, 10, 3123 DOI: 10.1039/C9SC00079H

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements