Tetrahydropyran synthesis by palladium(II)-catalysed hydroxycarbonylation of hexenols: synthesis of (±)-diospongin A and (+)-civet cat compound

A diastereoselective synthesis of 2,6-cis-tetrahydropyranyl acetic acids has been developed based on the palladium(II)-catalysed intramolecular hydroxycarbonylation of hexenols. This domino Pd-cyclisation/carbonylation/hydroxylation of (2S)-hept-6-en-2-ol 15 and O-TBDPS protected 1-phenylhex-5-en-1,3-diol 12, respectively, was used as a key step in the total syntheses of two natural products, civet cat (+)-2-[(2S,65)-(6-methyltetrahydro-2H-pyran-2-yl)] acetic acid 1 and diospongin A 2. Moreover, an efficient synthesis of 2 using a multi Pd-cyclisation/carbonylation/cross-coupling transformation has been achieved. (C) 2011 Elsevier Ltd. All rights reserved.