Acid-catalyzed spiroketalization reaction

We should also expect stereoelectronic control when the hydroxyl group is replaced by another nucleophile in the reaction with cyclic oxonium ions. A recent report (110) shows that hydride transfer to cyclic oxonium ion is subject to stereoelectronic control. Tricyclic spiroketal 140 (Fig. 19) undergoes an acid-catalyzed oxidation-reduction reaction to give the equatorial bicyclic aldehyde 147 stereospecifically. Similarly, spiroketals 148 and M9 gave the corresponding equatorial bicyclic ketone 150. 

A more detailed study27 was carried out of the spiroketalization reaction. Compounds obtained by C-23 deoxygenation of intermediates in the tetrahydrocephalostatin 12 synthesis were used, with various permutations differing in their C-20 stereochemistry and also the presence or absence of benzylation at C-26. These compounds were subjected to a series of acid-catalyzed cyclizations. 

The Brimble group reported the synthesis of acortatarin A 20 in 2012. As in the first synthesis of acortatarin A 20 by Sudhakar et al. a traditional acid-catalyzed dehydrative spiroketalization was used as one of the final steps. However, instead of performing the previously used disconnection between CIO and N9, as several other groups have reporteda Maillard-type condensation reaction between amino alcohol 50 and the sugar surrogate 51 would be used to give 49. The amine 50 would come from D-mannitol and 51 would be prepared from furfuryl alcohol on a gram scale (Scheme l )" ... 

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