alcohol 4 was subsequently subjected to bromination using
PBr , and the phosphonation of the resulting allylic bromide
3
Scheme 1. Retrosynthetic Analysis
under Michaelis-Arbuzov conditions provided the diethyl
allylphosphonate 5 (95% yield from 4, two steps). A
Horner-Wadsworth-Emmons olefination between the ob-
tained allylphosphonate and the R,â-unsaturated aldehyde
5
6
successfully led to the required (E,E,E)-trienic vinyl
stannane 7 in 53% yield. Therefore, the trienic alkenyl
stannane 7, precursor of the tetraenic moiety, was prepared
efficiently in four steps from aryl triflate 2 in 40% overall
yield (Scheme 2).
Then, we turned our attention toward the synthesis of vinyl
iodide 13, which commenced from a Negishi zirconium-
assisted carboalumination applied to 3-butyn-1-ol 8 (cat.
6
Cp
2
ZrCl
2
, Me
3
Al, H
2
O), thus affording the alkenyl iodide
9
in 77% yield. Oxidation of the resulting primary alcohol
with Dess-Martin periodinane (DMP) and subsequent treat-
ment of the obtained aldehyde with the highly face-selective
7
optically active allyltitanium complex (S,S)-I led to the
homoallylic alcohol 10 in 84% yield and with high enantio-
8
selectivity (ee > 95%). The latter enantiopure secondary
alcohol was then protected as a PMB ether using p-methoxy-
benzyl trichloroacetimidate, in the presence of camphorsul-
fonic acid (CSA), to furnish compound 11 in 63% yield. A
regioselective oxidative cleavage of the terminal double bond
4 4
(OsO /NMO, then NaIO ) produced the corresponding chiral
â-alkoxyaldehyde, which in turn could be directly converted
into vinyl ketone 12 by a series of classical transformations
(addition of vinylMgBr followed by oxidation with PCC;
47% yield, four steps). Finally, cleavage of the PMB ether
with DDQ afforded the desired â-hydroxy vinyl ketone 13
in 71% yield (Scheme 3).
olefinic partner 17 orthogonally protected at C25 would allow
the access to vinyl iodide 20 (Scheme 1).
The required trienic vinyl stannane 7 was synthesized from
3
the known aryl triflate 2, readily accessible from com-
mercially available 2-hydroxybenzoic acid (Scheme 2). The
Scheme 3. Stereoselective Synthesis of Vinyl Iodide 13
Scheme 2. Stereoselective Synthesis of Trienic Stannane 7
latter was first converted into the allylic alcohol 4 by
performing a Pd
the organotin compound 3 (82% yield). The resulting allylic
2 3
(dba) -catalyzed Stille cross-coupling with
The last required fragment, that is, the optically active
,3,5-triol 17, was synthesized in seven steps from the
4
1
(
3) (a) Hadfield, A.; Schweitzer, H.; Trova, M. P.; Green, K. Synth.
(5) â-Stannylacrolein 6 was synthesized by performing a regio- and
Commun. 1994, 24, 1025-1028. (b) Dushin, R. G.; Danishefsky, S. J. J.
Am. Chem. Soc. 1992, 114, 655-659. (c) F u¨ rstner, A.; Konetzki, I.
Tetrahedron 1996, 52, 15071-15078.
stereoselective stannylcupration of commercially available propiolaldehyde
diethylacetal followed by acetal hydrolysis according to: (a) Lipshutz, B.
H.; Lindsley, C. J. Am. Chem. Soc. 1997, 119, 4555-4556. (b) Lipshutz,
B. H.; Ullman, B.; Lindsley, C.; Pecchi, S.; Buzard, D. J.; Dickson, D. J.
Org. Chem. 1998, 63, 6092-6093.
(4) Wang, X.; Bowman, E. J.; Bowman, B. J.; Porco, J. A., Jr. Angew.
Chem., Int. Ed. 2004, 43, 3601-3605.
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Org. Lett., Vol. 9, No. 8, 2007