A mild, Large-scale synthesis of 1,3-cyclooctanedione: expanding access to difluorinated cyclooctyne for copper-free click chemistry

We report the large-scale synthesis of 1,3-cyclooctanedione in five steps with 29% yield. This molecule is a synthetic precursor to difluorinated cyclooctyne, which participates in a bioorthogonal copper-free click reaction with asides. The final step demonstrates the first successful application of the Wacker-Tsuji oxidation to form a cyclic 1,3-dione. (C) 2011 Elsevier Ltd. All rights reserved.