Approaching the C33-C38 Fragments of Amphotericin B and Nystatin by a Retro-[1,4]-Brook Rearrangement and the Stereoselective Manipulation of the Resulting Allylsilane

Sulfide S-4 (98.6% ee) furnished allylsilane S,S-anti-2 through a potassium naphthalenide induced, highly stereoselective retro-Brook rearrangement. Treatment with diethylborane followed by NaOOH/H2O2 delivered alcohol 9 as a single diastereomer. Cylization (→ 10), oxidation (→ 16), and methylation gave ketone 17. Reduction of 17 with Et3SiH in CF3CO2H was accompanied by an unprecedented rearrangement of the neighboring oxasilolane ring to the C-silylated tetrahydropyran 20. It was oxidized to alcohol 21 which - if one inverted its OH group - would become a new C33-C38 building block for the polyol/polyene antibiotics amphotericin B and nystatin.