Total Synthesis Highlights

78. Synthesis of Deacetoxyalcyonin Acetate
Deacetoxyalcyonin acetate 1 and euncellin 2 are representative members of the eunicellin class of
diterpenes. The synthesis of deacetoxyalcyonin acetate 2 by Gary Molander of the University of
Pennsylvania (J. Am. Chem. Soc. 2004, 126, 1642.) illustrates the power of intramolecular
organometallic carbonyl addition for ring construction.
The six-membered ring of 1 was commerically available in enantiomerically-pure form as
α-phellandrene 3. The challenge was to stitch the highly-substituted ten-membered ring of 1 onto
the disubstituted alkene of 3. The strategy that was conceived was to first construct the
seven-membered ring of 8, then effect three-carbon ring expansion to give 11.
The plan for seven-membered ring construction was to effect stepwise 4 + 3 cycloaddition of 6 to
the protected dialdehyde 5. The preparation of 5 began began with 2+2 cycloaddition between 3
and methoxy ketene, to give 4 with high regio- and diastereocontrol. Photochemical cleavage then
gave 5. The acid-mediated 4 + 3 proceeded via initial addition to the less congested ionized
aldehyde, to give the β-keto ester 7. Alkylation of the dianion of 7 followed by ester hydrolysis
and selenation /oxidation established the enone 8.