Issue 6, 2018

Stereoselective construction of sterically hindered oxaspirocycles via chiral bidentate directing group-mediated C(sp3)–O bond formation

Abstract

The systematic investigation of chiral bidentate auxiliaries has resulted in the discovery of a chiral 2,2-dimethyl-1-(pyridin-2-yl)propan-1-amine-derived directing group that enables stereoselective palladium(II)-catalyzed intramolecular C(sp3)–O bond formation. This new chiral directing group exhibited high reactivity in the activation of methylene C(sp3)–H bonds with excellent levels of stereoselectivity (a diastereomeric ratio of up to 39 : 1), which allowed the construction of a wide range of oxaspirocycles. Mechanistic investigations were also conducted to elucidate the reaction mechanism and understand the origin of the diastereoselectivity. DFT calculations suggest that only modest levels of diastereoselectivity are accomplished at the rate-determining C–H metalation–deprotonation step and the d.r. is further enriched at the reductive elimination step.

Graphical abstract: Stereoselective construction of sterically hindered oxaspirocycles via chiral bidentate directing group-mediated C(sp3)–O bond formation

Supplementary files

Article information

Article type
Edge Article
Submitted
31 Oct 2017
Accepted
26 Nov 2017
First published
27 Nov 2017
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., 2018,9, 1473-1480

Stereoselective construction of sterically hindered oxaspirocycles via chiral bidentate directing group-mediated C(sp3)–O bond formation

Y. Kim, S. Kim, D. Kang, T. Sohn, E. Jang, M. Baik and S. Hong, Chem. Sci., 2018, 9, 1473 DOI: 10.1039/C7SC04691J

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