GROB-ESCHENMOSER Fragmentation

This modification resulted in a yield improvement for the pentacyclization process from 47 % to 66 %. Treatment of the amino ether 192 with diisobutylaluminum hydride in refluxing toluene accomplished Eschenmoser-Grob fragmentation and reduction of the initially formed immonium ion, to give the unsaturated amino alcohol 193 in 86% yield. It was gratifying to find that 193 was the only product formed in this reaction. In the tetrahydropyran derivative, reduction of 192 to 193 is accompanied by about 15 % simple elimination. Displacement of the tosyl group in 196 gives sulfide 197, which is oxidized to sulfone 198. This material is metallated and coupled with enantiomerically pure aldehyde to secure the codaphniphylline skelton [74]. 

Unsaturated macrolides such as (115) or (117) (Scheme 38) have been synthesized by Eschenmoser using a fragmentation reaction as a key step. The tricyclic ketal carboxylate (114) can be cleaved as an amidinium salt to give (115) in excellent yield simply on heating. Similarly, the macrolide (117) with ( , )-configuration is obtained from (116). This decarboxylative double fragmentation represents a nine-center Grob type. 

Related reactions Eschenmoser-Tanabe fragmentation, Grob fragmentation ... 

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