SYNTHESIS OF DISCODERMOLIDE SUBUNITS BY S(E)2' ADDITION OF NONRACEMICALLENYLSTANNANES TO ALDEHYDES

Three subunits, 15, 29, and 34, of the immunosuppressant discodermolid e were prepared starting from -3-[(tert-butyldimethylsilyl)oxy]-2-meth ylpropanal ((S)-1) and the enantioenriched allenyl-stannanes (P)-2a, ( P)-2b, and (P)-31. The route to 15 involved BF3-promoted addition of s tannane (P)-2a to aldehyde (S)-1 which afforded the syn,syn-homopropar gylic alcohol adduct 3 in 97% yield. The derived p-methoxybenzylidene acetal 5 was treated with Red-Al to effect cleavage of the pivalate an d reduction of the double bond leading to the (E)-allylic alcohol 6. S harpless epoxidation and subsequent addition of Me2CuCNLi2 yielded the syn,syn,syn,anti stereopentad, diol 8. Protection of the secondary al cohol and oxidation of the primary gave aldehyde 12, which was treated with the alpha-bromo allylsilane 13 and CrCl2, followed by NaH to eff ect elimination to the diene 15. A similar sequence was employed to pr epare aldehyde 29. In this case aldehyde (S)-1 was converted to the an ti,syn-homopropargylic alcohol 20 by treatment with the allenyl indium reagent formed in situ from allenylstannane (P)-2b and InBr3. Epoxy a lcohol 24, prepared from alcohol 20 by the above-described sequence, w as reduced with Red-Al to afford diol 25. Protection of the secondary alcohol and oxidation of the primary completed the synthesis of 29. Th e anti,syn-homopropargylic alcohol 32 was obtained through addition of the allenic indium reagent, from allenylstannane (P)-31, to aldehyde( S)-1. Protection of the derived diol 33 as the p-methoxybenzylidene ac etal afforded the third subunit, acetylene 34. Addition of the lithio derivative of 34 to aldehyde 29 gave alcohol 35 with the carbinyl ster eochemistry needed for C7 of discodermolide as the major product.