A Unified Strategy for the Stereocontrolled Construction of Structurally Unusual Sesquiterpene Lactones. Asymmetric Synthesis of Vulgarolide and Deoxocrispolide

The bicyclic ketone (+)-17b reacts with
vinylmagnesium bromide from its exo face, thus enabling
exploitation of the anionic oxy-Cope rearrangement and direct
alkylation of the enolate so formed with ethyl iodoacetate
to provide 24 in an efficient, stereocontrolled manner.
Tricyclic lactone 26b, readily produced from
24, proved to
be a common precursor to both synthetic targets. The construction
of vulgarolide (9) proceeded by transforming
the
SEM group in 26b into a mesylate for the purpose of
conversion to epoxy acid 39 in advance of oxidative
cleavage
of the double bond. This transformation resulted in direct
conversion to 9 and its epimer 42. Central
to the companion
synthesis of deoxocrispolide (4) was the ability of
37 to undergo the Michael addition of methoxide ion and of
54
to experience regiocontrolled dehydration to bridgehead olefin
55 in a protocol that involves the smooth
translocation
of bridgehead unsaturation with concomitant functionalization as an
allylic alcohol.