Syntheses of derivatives of L-daunosamine and its C-3 epimer employing as the key step the asymmetric conjugate addition of a homochiral lithium amide to tert-butyl (E,E)-hexa-2,4-dienoate

The highly diastereoselective asymmetric conjugate addition of lithium (R)-N-benzyl-alpha-methylbenzylamide to methyl or tert-butyl (E,E)-hexa-2,4-dienoate, followed by osmium tetroxide-catalysed dihydroxylation of the resulting adducts, provides a concise route to methyl L-daunosaminide hydrochloride and methyl 3-epi-D-daunosaminide hydrochloride, a strategy which is applicable to the synthesis of either enantiomer of these compounds. The selectivity of the key dihydroxylation reaction can be significantly improved by employing the Sharpless asymmetric dihydroxylation protocol. Possible alternative strategies using iodolactonisation or iodocyclocarbamation reactions as the key step were found to be much less satisfactory, due to either low selectivity, or the excessive number of steps that would be required.