Rizzacasa et al. [45] used this method in their synthesis of the Streptomyces
violaceusniger metabolite spirofungin A, 10 (Scheme 4). However, dehydrative
spirocyclization of ketone 6 afforded the undesired singly anomeric isomer 7b as
the major product, as it is less sterically hindered than the desired isomer 7a, and
therefore the thermodynamically favored isomer. Elaboration to the alkyne
spiroacetals 8a and 8b did not significantly change the inherent thermodynamic
preference for the singly anomeric isomer; however upon removal of the
TBS-ether, intramolecular hydrogen bonding (that was not possible in the singly
anomeric isomer) enabled equilibration of the mixture to access predominantly the
desired doubly anomeric isomer 9a.
Smith and coworkers have used a Ca(II)-mediated equilibration strategy to
access the singly anomeric CD spiroacetal of spongistatin-1, 15 [26] (Scheme 5).
Oxidative removal of the dithiane 11 and subsequent spirocyclization afforded
spiroacetals 12a and 12b in excellent yield, favoring the undesired doubly anomeric
Scheme 4 Rizzacasa et al.’s synthesis of spirofungin A [45]
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M.A. Brimble and L.A. Stubbing