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

Abstract

<p>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 <i>tert</i>-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 <i>cis</i>-buten-1,4-diol into complex tetrahydrofurans <i>via </i>a process involving <i>thermal </i>Cope rearrangement, Boc-deprotection, and <i>oxy</i>-Michael addition. Described herein includes background related to the discovery, optimization and scope, and representative functional group interconversion chemistry for the scaffolds. </p>