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Total Synthesis of (+)-Cochlearol B by an Approach Based on a Catellani Reaction and Visible-Light-Enabled [2+2] Cycloaddition.

Authors:
Alistair D Richardson Trenton R Vogel Emily F Traficante Kason J Glover Corinna S Schindler

Angew Chem Int Ed Engl 2022 08 23;61(31):e202201213. Epub 2022 Jun 23.

Department of Chemistry, University of Michigan, Willard Henry Dow Laboratory, 930 North University Ave., Ann Arbor, MI 48109, USA.

A 14-step synthesis of (+)-cochlearol B is reported. This renoprotective meroterpenoid features a unique core structure containing a densely substituted cyclobutane ring with three stereocenters. Our strategy employed an organocatalytic Kabbe condensation in route to the key chromenyl triflate. A subsequent Catellani reaction incorporated the remaining carbon atoms featured in the skeleton of cochlearol B. An ensuing visible-light-mediated [2+2] photocycloaddition closed the cyclobutane and formed the central bicyclo[3.2.0]heptane core. Notably, careful design and tuning of the Catellani and photocycloaddition reactions proved crucial in overcoming undesired reactivity, including cyclopropanation reactions and [4+2] cycloadditions.

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http://dx.doi.org/10.1002/anie.202201213DOI Listing
August 2022

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