Angewandte
Chemie
iPr2NEt), however, proceeded much
more efficiently. Desilylation of the
resulting ether with Py·HF yielded the
C3,C19 diol in 80% yield from 20.
Selective oxidation of the primary
allylic C3 alcohol with TEMPO and
[26]
PhI(OAc)2
formed aldehyde 21 in
87% yield. Macrolactone formation
was most conveniently accomplished
through an intramolecular Horner–
Emmons reaction,
a
parallel of
Smithꢀs approach[3] to this system. Acy-
lation of the hydroxyl group at C19
with diethylphosphonoacetic acid and
DCC provided the corresponding
phosphonoacetate, which, upon depro-
tonation with NaHMDS, engaged in an
intramolecular condensation reaction
to provide macrolactone 22 in 73%
yield from 21. The synthesis was com-
pleted by an oxidative cleavage of both
protecting groups with DDQ. This
process provided the C7,C20 diol
along with variable amounts of the C7
ketone. The allylic oxidation proved to
be inconsequential as the following
step was a double oxidation of the
diol with the Dess–Martin periodi-
nane[27] to provide dactylolide in 77%
yield ([a]D = + 1638, c = 0.29, MeOH).
In summary, we have reported an
efficient total synthesis of dactylolide.
Key steps in the sequence include two
Scheme 3. a) (1) TMSCl, imidazole, DMAP, DMF; (2) 6, TMSOTf, CH2Cl2, ꢀ788C, 83%;
b) 1) Me3SiCH2MgCl, CeCl3, THF, ꢀ788C!RT; 2) Py·HOTf, MgSO4, CH2Cl2, 75%. TMS=trime-
thylsilyl, DMAP=4-dimethylaminopyridine, Tf=trifluoromethanesulfonyl, Py (py)=pyridine,
LA=Lewis acid.
enantioselective
Mukaiyama reactions, fragment cou-
pling through acetal formation,
vinylogous
a
sequential Peterson olefination/Prins
cyclization reaction that proceeds
under very mild conditions, and a
Mislow–Evans
rearrangement
to
Scheme 4. a) (1) PhSeCN, Bu3P, THF; (2) H2O2, py, THF, ꢀ308C, 62%; b) (1) PMBOCH2Cl,
iPr2NEt, CH2Cl2; (2) HF·Py, py, THF, 80%; c) PhI(OAc)2, TEMPO, CH2Cl2, 87%; d) Diethylphos-
phonoacetic acid, DCC, DMAP, CH2Cl2, 95%; e) NaHMDS, THF, ꢀ78 !08C, 73%; f) DDQ,
CH2Cl2, buffer (pH 7), 63% (14% C7 ketone); g) Dess–Martin periodinane, CH2Cl2, 77%.
TEMPO=2,2,6,6-tetramethylpiperidinyl-1-oxyl, DCC=dicyclohexyl carbodiimide, HMDS=hexa-
methyldisilazide, DDQ=2,3-dichloro-5,6-dicyano-1,4-benzoquinone.
effect the transposition of an allylic
alcohol. The linear sequence was kept
as brief as possible by minimizing
carbon–carbon bond-forming reactions
and employing a convergent approach.
As both antipodes of the catalysts that
into a selenide with PhSeCN and Bu3P[20], with no complica-
tion from the SN2’ pathway. Oxidation of the crude selenide
with H2O2 in the presence of pyridine induced a selenium
variant[21] of the Mislow–Evans rearrangement[22] to provide
allylic alcohol 20 in 62% yield over the two-step sequence.[23]
While the stereochemical outcome of this reaction was not
rigorously established, mechanistic analogy[24] strongly sug-
gests that the nascent alcohol is oriented as shown in
Scheme 4. Attempts to form the PMB ether of the hydroxyl
group at C7 under basic (NaH, PMBCl, NaI) or acidic
(PMBOC(NH)CCl3, BF3·OEt2, or TfOH) conditions resulted
in low conversions and significant decomposition. Formation
of the p-methoxybenzyloxymethyl ether[25] (PMBOCH2Cl,
were used to establish stereogenicity are available, this
sequence is also applicable to the synthesis of zampanolide
through the use of Hoyeꢀs aza-aldol reaction.
Received: February 15, 2005
Published online: April 21, 2005
Keywords: allylic compounds · asymmetric synthesis ·
.
carbocations · natural products · rearrangement
[1] A. Cutignano, I. Bruno, G. Bifulco, A. Casapullo, C. Debitus, L.
Gomez-Paloma, R. Riccio, Eur. J. Org. Chem. 2001, 775 – 778.
Angew. Chem. Int. Ed. 2005, 44, 3485 –3488
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3487