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Convergent Synthesis of Trisubstituted Tetrahydrofurans via Bis-Thermally Reactive 1,5-Diene-Tert-Butyl Carbonates.

submitted on 31.10.2019, 15:12 and posted on 06.11.2019, 21:53 by Alex Grenning, Fabien Emmetiere

Cascade reactions (also known as domino- or tandem reactions) are an efficient strategy for generating molecular complexity. We report that synergizing the thermal reactivity of 3,3-dicyano-1,5-dienes and tert-butyl carbonates result in stereospecific 2,3,4-trisubstituted tetrahydrofuran synthesis. While substituted tetrahydrofurans can be challenging to synthesize, this discovery converts readily available 1,5-dienes derived from aldehydes, malononitrile, and cis-buten-1,4-diol into complex tetrahydrofurans via a process involving thermal Cope rearrangement, Boc-deprotection, and oxy-Michael addition. Described herein includes background related to the discovery, optimization and scope, and representative functional group interconversion chemistry for the scaffolds.


This material is based upon work supported by the National Science Foundation under Grant No. 1844443


Email Address of Submitting Author


University of Florida


United States of America

ORCID For Submitting Author


Declaration of Conflict of Interest

No Conflict of Interest

Version Notes

This is Version 1 of this Manuscript