Highly Selective and Modular Assembly of Densely Substituted Tetrahydrofurans.

Authors

Yan-Bo Li, Colin Stein, Shuyao Zhou, Daniel Thielemann, Tobias J Stoffels, Niklas Hölter, Leopold A Kellermann, Constantin G Daniliuc, K N Houk, Frank Glorius

Published in

Journal of the American Chemical Society. Jul 10, 2026. Epub Jul 10, 2026.

Abstract

Densely substituted heterocycles are ubiquitous motifs in both natural products and pharmaceuticals. sp³-Heterocycles bearing multiple vicinal stereocenters are especially critical targets due to their challenging construction under precise stereocontrol. The multisubstituted tetrahydrofuran (THF) family, for example, represents a privileged structural motif. Yet, syntheses of THFs are often step-intensive and tailored to a single target structure, as generalized and robust methods that rapidly introduce multiple substituents from simple precursors remain underdeveloped. Herein, we present a distinct approach featuring two core advantages: modular assembly from abundant building blocks, and precise chemo-, regio-, diastereo-, and enantioselectivity. Pivotal to the success of this methodology is synergistic metallaphotoredox-Lewis acid catalysis, which rapidly constructs four bonds in THFs bearing up to four stereocenters. Experimental and computational studies deliver further insight into the mechanism. High-throughput experimentation (HTE) highlights the potential for efficient generation of THF-based libraries.

PMID:
42429033
Bibliographic data and abstract were imported from PubMed on 10 Jul 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.