Stereochemically Versatile Synthesis of the C1-C12 Fragment of Tedanolide C
Smith, T.E.; Fink, S. J.; Levine, Z. G.; McClelland, K. A.; Zachheim, A. A.; Daub, M. E. Stereochemically Versatile Synthesis of the C1-C12 Fragment of Tedanolide C. Org. Lett. 2012, 14, 1452-1455.
A flexible synthesis of the C1-C12 fragment of Tedanolide C has been accomplished in eight steps from 2-methyl-2,4-pentadienal. Asymmetric hydroformylation of a 1,3-diene allows for the late-stage generation of either C10 epimer with complete catalyst control. Diastereoselective addition of an isobutyryl β-ketoester dianion to an α,β-disubstituted chiral aldehyde sets the C5 stereochemistry while installing the geminal dimethyl unit. Differential protection of a syn-1,3-diol is performed as a highly efficient single-pot operation.