Diversity Oriented Synthesis of Macrocyclic Diaryl Ethers by Dötz Benzannulation

Abstract

We aimed to synthesize novel macrocycles based upon structures type A and B (Scheme 1). Both of them have diaryl ether linkages that provide rigidity to the system. Inspired by polycyclic ethers as natural products, ether linkag-Abstract: The intramolecular Dçtz benzannulation with alkyne-tethered aryloxy Fischer carbenes has been applied to synthesize a nine membered diaryl ether linked macrocyclic library. In silico tools, that is, shape space analysis was used to assess the diversity of the library, and polar surface area (PSA) of the compounds were deduced to understand the range of their surface electrostatic potential.Scheme 2. "Build/couple/pair" synthetic strategy. Scheme 3. Build phase: synthesis of phenols 2-6. DIAD = diisopropyl azodicarboxylate Scheme 4. Coupling to generate alkyne-tethered aryloxy carbenes. 863 www.AsianJOC.org Subhabrata Sen et al. Scheme 5. Pairing towards the macrocycles. Scheme 6. Postpairing. DMSO = dimethyl sulfoxide.