Terpene Cyclase Mimicking Chlorine-Induced Polyene Cyclizations

• Published in: ChemRxiv
• Main Authors: Binder, Julia, Gulder, Tanja
• Format: Paper
• Language: English
• Edition: 1
• Subjects: Chemistry; Natural Products; Organic Chemistry; Organic Compounds and Functional Groups; Organic Synthesis and Reactions; hypervalent iodane; halogenation; HFIP; biomimetic synthesis; polyene cyclization; terpenes
• ISSN: 2573-2293
• DOI: 10.26434/chemrxiv-2022-7880k

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.