Alcohols as Efficient Intermolecular Initiators for a Highly Stereoselective Polyene Cyclisation Cascade

Abstract

The use of benzylic and allylic alcohols in HFIP solvent together with Ti(OiPr)4 has been shown to trigger a highly stereoselective polyene cyclisation cascade. Three new carbon‐carbon bonds are made during the process and complete stereocontrol of up to five new stereogenic centers is observed. The reaction is efficient, has high functional group tolerance and is atom‐economic generating water as a stoichiometric by‐product. A new polyene substrate‐class is employed, and subsequent mechanistic studies indicate a stereoconvergent mechanism. The products of this reaction can be used to synthesize steroid‐analogues in a single step.

Difunctionalization Processes Enabled by Hexafluoroisopropanol

“…Here, the mechanism first involves the activation of sulfenylating agent 16 by HFIP, which then facilitates sulfur transfer to selenophosphoramide catalyst (S)-17. The next step is the transfer of the sulfenyl group to the alkene to form thiiranium ion 27, which undergoes a stereospecific intramolecular nucleophilic capture (28) and a subsequent deprotonation to afford the product. The previously described catalytic system for sulfenocyclization was also employed to perform intermolecular sulfenoamination of alkenes (Scheme 4).…”

“…More recently, the group of Donohoe described another highly stereoselective class of transformations driven by HFIP�polyene cyclization cascades�with primary and secondary allylic and benzylic alcohols (Scheme 7). 28 This way, even much more complex all-carbon scaffolds could be prepared in a single step under the above-mentioned conditions. The reaction worked effectively with a variety of electron-neutral and electron-rich arenes.…”