New synthetic strategy to create intricate thiaoxacyclophanes via ring-closing metathesis

This study explores a thiol-free, two-step synthetic strategy to intricate thiacyclophanes from bromoaryl precursors. Our methodology involves a one-pot substitution reaction of aryl bromides with potassium thioacetate (PTA) followed by ring-closing metathesis (RCM). Potassium thioacetate is advantageous over other sulfur-containing reagents like sodium sulfide, sodium hydrosulfide, and sodium hydroxymethylsulfinate (rongalite), etc., as it generates a stable and odorless thioacetate intermediate which allows access to a variety of symmetrical and unsymmetrical sulfides. These sulfides undergo RCM to generate new thiacyclophanes. Applying this methodology, we have created 24 new oxa-thiacyclophanes and aza-oxa-thiacyclophanes containing different aromatic and aliphatic units. The structures and stereochemistry of these cyclophanes are confirmed by NMR data and further supported by single-crystal X-ray diffraction data.