C O M M U N I C A T I O N S
The synthesis of 2 was accomplished in seven linear steps, using
a total of 12 synthetic operations from easily accessible chemicals.
The synthesis of 3 was completed in 11 total steps using a one-pot
Stille/Suzuki-Miyaura reaction sequence as the key step. This
convergent one-pot sequence was first developed during methodol-
ogy studies with aryl iodide substrates,9 but this is the first time it
has been implemented in a natural product synthesis. The total
syntheses of 2 and 3 are synthetically efficient, potentially versatile,
and exceptionally convergent.
coupling with vinyl iodide 7 to afford directly (6E)-O-methylmy-
xalamide (2), spectrally identical with the natural product.1,22
Acknowledgment. This work was supported by a grant from
the National Cancer Institute (NIH CA91904).
Supporting Information Available: Experimental procedures and
characterization of compounds. This material is available free of charge
References
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(16) The ratios of enantiomers of 12 (90:10) and 7 (90:10) were determined
separately by NMR analysis of corresponding Mosher esters.
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The completion of the synthesis of 3 now became a straightfor-
ward task of sequential cross-coupling reactions, in this instance
in a one-pot fashion: palladium-promoted Stille coupling between
triene 6 and right-hand vinyl iodide 8 followed by the addition of
left-hand vinyl iodide 7 and base to promote Suzuki-Miyaura
coupling. This procedure directly afforded 3 in good yield for this
complex reaction process. Most importantly, the one-pot protocol
avoided possible isomerization of an intermediate tetraene species
during isolation and purification. Double bond isomerization was
not observed during the coupling reaction, or isolation, purification,
or characterization, and 3 was obtained as a single stereoisomer.
The spectral data of 3 were in excellent agreement with that reported
for the natural product.1,22
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