would derive from the Stille coupling11 of vinyl iodide 4
and (Z)-vinylstannane 5.
The synthesis of fragment 4 began with the asymmetric
allylboration17 of aldehyde 13,18 which provided the known
homoallylic alcohol 1419 in 99% yield with 88% ee (Scheme
3). Compound 14 was then subjected to olefin cross-
Construction of fragment 5 began with the asymmetric
(E)-crotylboration12 of aldehyde 613 (Scheme 2), which gave
Scheme 3. Synthesis of Vinyl Iodide Fragment 4a
Scheme 2. Synthesis of Vinyl Stannane 5a
a Conditions: (a) (dIpc)2B-crotyl, THF, -78 °C, then NaBO3‚H2O.
(b) TBS-OTf, 2,6-lutidine, CH2Cl2, -78 °C. (c) 9-BBN, THF, then
aqueous NaOH/H2O2. (d) n-BuLi, THF, -50 °C, then I2. (e)
o-Nitrobenzenesulfonylhydrazide, Et3N, THF/i-PrOH (1:1). (f)
SO3‚pyr, DMSO, iPr2NEt, CH2Cl2, 0 °C. (g) Trimethyl phosphono-
acetate, LiCl, Et3N, CH3CN. (h) DIBAL-H, CH2Cl2. (i) MeLi, Et2O,
-40 to 23 °C; n-BuLi, -78 °C; then Me3SnCl, THF, -78 °C.
a Conditions: (a) (dIpc)2B-allyl, THF, -78 °C; see ref 17. (b)
Methyl acrylate (3 equiv), Hoveyda catalyst A (1.5 mol %), CH2Cl2,
reflux. (c) PhCHO, tBuOK, THF, 0 °C. (d) (HF)3‚Et3N, CH3CN,
40 °C. (e) SO3‚pyr, DMSO, iPr2NEt, CH2Cl2, 0 °C. (f) CrCl2, CHI3,
dioxane/THF (6:1). (g) (i) 80% AcOH, THF, 95 °C; (ii) Amberlite
IRA-400(OH), MeOH; (iii) TBS-OTf, 2,6-lutidine, CH2Cl2, -78
°C. (h) DIBAL-H, CH2Cl2, -78 °C. (i) Ethyl diazoacetate, SnCl2,
CH2Cl2.
the anti homoallylic alcohol 7 (90% ee) in 66% yield.
Protection of the hydroxyl group of 7 as a TBS ether (90%
yield) and then hydroboration of the vinyl group with 9-BBN
and cleavage of the alkynylsilane unit during oxidation of
the alkylborane provided primary alcohol 8 in 84% yield.
This intermediate was iodinated in 94% yield by treatment
with n-BuLi in THF (-50 °C) and then I2. (Z)-Vinyl iodide
10 was then prepared in 90% yield by reduction of alkynyl
iodide 9 with diimide (generated in situ from o-nitrobenzene-
sulfonylhydrazide and Et3N).14 Oxidation of primary alcohol
10 by using the Parikh-Doering protocol15 gave the corre-
sponding aldehyde, which was subjected to standard Horner-
Wadsworth-Emmons olefination16 to give ester 11 in 91%
yield for the two steps. Reduction of 11 with DIBAL-H gave
allylic alcohol 12 in 99% yield. Finally, sequential treatment
of 12 with MeLi (Et2O, -78 °C) and then n-BuLi (-78 °C),
followed by addition of Me3SnCl then provided vinyl-
stannane 5 in 77% yield.
metathesis with methyl acrylate using Hoveyda’s catalyst
(A)20 to give the R,â-unsaturated ester 15 in 86% yield as
the (E)-isomer. The benzylidene-protected syn-1,3-diol 16
was then prepared in 89% yield by treatment of 15 with
benzaldehyde and a catalytic amount of t-BuOK in THF.21
After removal of the TBDPS ether (82% yield), the primary
alcohol was oxidized to give aldehyde 17 in 92% yield. This
intermediate was then converted into (E)-vinyl iodide 18 in
61% yield via the Takai olefination reaction.22,23 Having
served its intended purpose, the benzylidene acetal unit of
(17) Racherla, U. S.; Brown, H. C. J. Org. Chem. 1991, 56, 401.
(18) Boeckman, R. K., Jr.; Charette, A. B.; Asberom, T.; Johnston, B.
H. J. Am. Chem. Soc. 1987, 109, 7553.
(11) Stille, J. K.; Groh, B. L. J. Am. Chem. Soc. 1987, 109, 813.
(12) Brown, H. C.; Bhat, K. S. J. Am. Chem. Soc. 1986, 108, 5919.
(13) Komarov, N. V.; Yarosh, O. G.; Astaf’eva, L. N. J. Gen. Chem. U.
S. S. R. 1966, 36, 920.
(14) Chavez, D. E.; Jacobsen, E. N. Angew. Chem., Int. Ed. 2001, 40,
3667.
(15) Parikh, J. R.; Doering, W. v. E. J. Am. Chem. Soc. 1967, 89, 5505.
(16) Blanchette, M. A.; Choy, W.; Davis, J. T.; Essenfeld, A. P.;
Masamune, S.; Roush, W. R.; Sakai, T. Tetrahedron Lett. 1984, 25, 2183.
(19) Smith, A. B., III; Safonov, I. G.; Corbett, R. M. J. Am. Chem. Soc.
2002, 124, 11102.
(20) Cossy, J.; BouzBouz, S.; Hoveyda, A. H. J. Organomet. Chem. 2001,
624, 327.
(21) Evans, D. A.; Gauchet-Prunet, J. A. J. Org. Chem. 1993, 58, 2446.
(22) Takai, K.; Nitta, K.; Utimoto, K. J. Am. Chem. Soc. 1986, 108,
7408.
(23) Evans, D. A.; Ng, H. W.; Riegler, D. L. J. Am. Chem. Soc. 1993,
115, 11446.
2044
Org. Lett., Vol. 6, No. 12, 2004