Selectivity in the Reduction of Natural Products

There are many synthetic examples where hydride reduction of complex molecules proceeds with high dia-stereoselectivity. Reduction of 326a to alcohol 327 with lithium tri-tert-butoxyaluminum hydride is taken from Donaldson s synthesis of the C3-C15 bis(oxane) segment of phorboxazole. Oi The conformational drawing (326b) reveals that path a is preferred in the more stable chair conformation with the two substituents in the equatorial position. This model predicts the major alcohol product, which was converted as the acetate. 

Another example is Overman s reduetion of 328a to give 329 in 92% yield with L-Seleetride, as part of a synthesis of (+)-seopaduleie aeid The 3D modeP (328b) shows the seven-membered ring with a large 

Reduction of norbornane-like precursors to natural products is also predictable. Reduction of the ketone unit in 330, in Money s synthesis of 3-santalene for example, gave the exo-alcohol 331 via attack from the less hindered endo face. Conversely, removal of the steric encumbrance at C7 (as in 332) gave attack via the exo face to give 333 (in about a 4 1 ratio favoring the endo alcohol shown). 4 

There are many more examples of selectivity in reduction. These few are simply meant to illustrate that the simple principles discussed in this section, and the models used, can be applied to more complex systems with reasonable success. 

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