A synthesis
of (+)-xylogiblactone A has been achieved from t-butyl
2-methylbuta-2,3-dienoate in a linear three-step
sequence. The key elements of the synthesis include a kinetic resolution
of racemic 2-silyoxyaldehyde through the allenoate γ-addition
to yield the γ-adduct as a single isomer and the subsequent
gold catalysis to form the butenolide core. For a general method,
the kinetic resolution of several racemic 2-silyloxyaldehydes is also
performed to provide products in high levels of stereoselectivity
with unusual anti-Felkin–Anh addition fashion.
A synthesis of (+)-hypoxylactone has been accomplished in four steps starting from the allenoate γ-addition of threo-3-chloro-2-silyoxybutanals, leading to the revision of stereochemistry. The key was the discovery of control elements required to matching/mismatching cases in the allenoate γaddition to provide the desired adducts as a single isomer. The utility of the γ-adduct was demonstrated with the Au(I)-catalyzed cyclization to afford (+)-xylogiblactone A. Use of Ag 2 O was the key to epoxidation for preventing epimerization of the γ-lactone ring.
Concise syntheses of naturally occurring γ-butenolides
(+)-xylogiblactones
B and C have been achieved for the first time starting from commercial
methyl crotonate in 5–8 steps. The synthetic course involves
allenoate γ-addition to racemic aldehydes through a kinetic
resolution to establish the required stereochemical framework as center
and axial chirality and subsequent oxacyclization via gold catalysis
to complete the (+)-xylogiblactone skeleton. Both key transformations
proceed in a regio- and stereospecific manner. This outcome relies
on finding an efficient synthetic method for racemic aldehydes as
precursors for the kinetic resolution. Completion of the synthesis
provides stereochemical clarification for (+)-xylogiblactones B and
C.
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