Construction of Unusual Amino Acid derivatives and Bis‐Fused Oxacycles via Ring‐Closing Metathesis

Abstract

Benzofurans and benzoxepines are key structural elements present in several natural products and medicinally important targets. Here, we describe an easy‐to‐execute strategy for the synthesis of benzofurans and benzoxepines, by employing Claisen rearrangement and ring‐closing metathesis (RCM) as key steps. Amino acid L‐tyrosine and 1,8‐dihydroxy‐anthraquinone were converted into modified oxacycles in good yields. The RCM approach has been used to produce bis‐fused benzofuran, bis‐fused benzoxepine, and unusual α‐amino acid (AAA) derivatives containing heterocyclic units. Unusual AAA derivatives are among the most important source for new peptide drugs and these AAA derivatives containing oxacycles are useful in designing many natural and unnatural products. Bis‐fused benzofuran and bis‐fused benzoxepine derivatives were also synthesized by the application of double Claisen rearrangement and two‐directional RCM as key steps starting with 1,8‐dihydroxy anthraquinone.

Selectivity: A Goal for Synthetic Economy

“…This selectivity might have originated from differential steric effects experienced by different allyl groups (Scheme 3 ). 12…”