Terpene Cyclase Mimicking Chlorine-Induced Polyene Cyclizations

23 March 2022, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

Nature forges a plethora of structurally divers polyenes with high efficiency and selectivity in a single cyclization step from achiral precursor. Imitating this powerful strategy has been the subject of numerous synthetic efforts. While bromo- and iodocyclizations have recently been successfully implemented, chlorocyclizations have been scantly investigated. Here, we present a selective and generally applicable biomimetic concept on a direct chlorination-induced polyene cyclization by utilizing a confined HFIP-chlorenium network inspired by the enzymatic pocket of terpene cyclases. Chloro-iodanes proved to be superior as electrophilic chlorine source. Together with catalytic amounts of saccharine in HFIP, a manifold of different alkenes with various inter- and intramolecular nucleophiles were converted with high yields and selectivities (up to 78% yield and d.r. >95:5). The cyclization platform was even extended to several structurally challenging terpenes and terpenoid carbon frameworks. NMR experiments revealed attractive non-covalent interactions between the F-alcohol and the lactone moiety in chloro-iodanes that are probably facilitating the chlorocyclization. The present results mark another milestone in the biomimetic cyclization of polyenes, allowing direct and selective access to these powerful molecules.

Keywords

polyene cyclization
terpenes
halogenation
hypervalent iodane
HFIP
biomimetic synthesis

Supplementary materials

Title
Description
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Title
Terpene Cyclase Mimicking Chlorine-Induced Polyene Cyclizations
Description
Supplementary data including additional studies, experimental procedures and compound characterizations.
Actions
Title
Terpene Cyclase Mimicking Chlorine-Induced Polyene Cyclizations
Description
Supplementary data including NMR spectra of the compounds discussed.
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