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Transformation from intermediate 3 to 4 in the synthesis of Vinigrol

Maimone, T. J.; Shi, J.; Ashida, S.; Baran, P. S. J. Am.Chem. Soc. 2009, 131, 17066-17067.

 

Explain the stereochemistry (stereoselectivity) observed during the transformation of 3 into 4.

 

Step 1.
For the first step, a hydrogen is removed and replaced with a methyl group using LDA (a strong base) and Methyl Iodide.  The stereochemistry predicted for this reaction is S, because of the steric hindrance involved when trying to remove the Hydrogen coming out of the plane of the page.  Also, the more stable chair conformation is most likely with the “back” Hydrogen projected in the equatorial position, which makes it that much easier to remove with LDA.

 

Step 2.
For the second step, there are no stereochemical considerations because the OTBS group is just being replaced by an OH group.  There are no stereocenters involved.

 

Step 3.
For the third step, the carbonyl Carbon is first protonated using Me4NBH(OAc)3 and then quenched with NH4Cl.  This step also has stereochemical considerations, because of the steric effects of the ring and the isopropyl group.  Because of these two large groups, it would be difficult for the Me4NBH(OAc)3 to protonate the top side of the carbonyl, so the bottom side, and the R configuration, is greatly preferred.  The quenching of the oxygen anion with HCl does not have stereochemical considerations.