Stereochemistry of Compound 29

Spiroketalization reactions often involve the use of an acid catalyst, which serves to protonate the carbonyl functional group, this activates the carbon center, as it becomes more electrophilic. This is followed by a nucleophilic attack by a hydroxyl group, which is later deprotonated. The result is a spiroketal. These compounds are founds in numerous natural products and exhibit a wide range of biological activities. The synthesis of products that contain spiroketals often involved thermodynamic controlled reactions. In such reactions, the stereochemistry of the resulting compound depends on competing factors that govern stability. In order to increase the stereodiversity, kinetically controlled reactions are used.
This particular reaction involved a nucleophilic hydroxyl attack on a carbocation that is resonance stabilized by an adjacent oxygen atom. This carbocation is formed by the nucleophilic attack of a carbon-carbon double bond on benzeneselenenyl bromide. An adjacent oxygen atom serves to resonance stabilize the carbocation that forms. The hydroxyl nucleophilic attack follows since the carbon in the carbonyl is activated. The hydroxyl group is deprotonated following this attack.
The resulting stereochemistry of the spiroketal involves the newly formed carbon oxygen bond on a dash. In addition, the tert-butyldiphenylsilanoate group is orientated on a wedge as opposed to a dash. A possible explanation for this stereochemical outcome is sterics. The two methyl groups adjacent to the nucleophilic hydroxyl group would experience steric repulsions with the methyl and bromine group on the tetrahydropyran if the hydroxyl group attacks from the front. When the hydroxyl group attacks from behind, the carbon-carbon bond with tert-butyldiphenylsilanoate group can rotate out. This allows the new carbon oxygen bond to be nearly axial with the ring. As a result, the two methyl groups adjacent to the oxygen are positioned so that they experience no steric hindrance.

 

 

 

 

 

 

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