Tetrahydrofuran (THF) rings are an important structural motif in organic chemistry. They can be found in various natural product classes, for example, in lignanes or polyketides. They are also an important synthetic tool for installing oxygen functionalities in steroids or terpenes. In polymer chemistry, THF serves as a valuable monomer for poly(tetramethylene oxide) (PTMO) polymers. An atom-economical way to synthesize THF rings is based on converting alcohols via intramolecular cyclization reactions. However, these reactions usually require either toxic heavy metals or an excess of oxidation reagents.
Vanessa Koch and Stefan Bräse, Karlsruhe Institute of Technology (KIT), Germany, have found a metal-free pathway for the transformation of alcohols into THF derivatives via C–H activation, using economically and ecologically favorable iodine reagents. The researchers developed an iodine-catalyzed cyclization reaction with high regioselectivity (pictured) that favors the formation of five-membered THF rings over the thermodynamically more stable six-membered rings (tetrahydropyrans). The team used 10 mol% iodine together with PhI(mCBA)2 (mCBA = meta-chlorobenzoate) as an oxidizing reagent under a floodlight, direct exposure to daylight, or LED lamps.
The reaction is operationally simple and proceeds under mild conditions. Non-functionalized alcohols can be transformed into THF derivatives with yields up to 71 %. More complex molecules like steroids or menthol could also be successfully converted.
- An intramolecular iodine‐catalyzed C(sp3)–H oxidation as a versatile tool for the synthesis of tetrahydrofurans,
Vanessa Koch, Stefan Bräse,
Eur. J. Org. Chem. 2021.