Synthesis of Intermediates 147 and

With an oxygen-bearing stereocenter in proximity to the C-16 ketone carbonyl in 155, the prospects for achieving a diastereose-lective ketone reduction seemed favorable. From the work of Mori and Suzuki, it was known that similarly constituted ketones are amenable to /i-chelation-controlled reductions with lithium alumi- 

A short digression is in order at this juncture. The electrophilic substitution of a vinylsilane is a very useful process because it is generally both regio- and stereospecific. The carbon-silicon bond is strongly polarized due to the high electronegativity of carbon (2.35) relative to silicon (1.64).67b A unique and important conse- 

-78 - 0 °C (mixed anhydride formation then 

The oxirane ring in 175 is a valuable function because it provides a means for the introduction of the -disposed C-39 methoxy group of rapamycin. Indeed, addition of CSA (0.2 equivalents) to a solution of epoxy benzyl ether 175 in methanol brings about a completely regioselective and stereospecific solvolysis of the oxirane ring, furnishing the desired hydroxy methyl ether 200 in 90 % yield. After protection of the newly formed C-40 hydroxyl in the form of a tert-butyldimethylsilyl (TBS) ether, hydrogenolysis of the benzyl ether provides alcohol 201 in 89 % overall yield. 

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