Chemistry Letters 2000
81
ments 4 and 5.
Conversion of 6 to 4 is outlined in Scheme 4. Silylation of
6 with TIPSOTf and 2,6-lutidine gave 19. Acetonide of 19 was
then removed under mild conditions using silica supported
FeCl3.8 Selective acetylation9 of the primary hydroxyl of the
resulting diol 20 was followed by MEM-protection of the sec-
ondary hydroxyl and deacylation to give the intermediate 21.
A standard 3-step protocol was carried out next to make one
2
3
J. Kobayashi and M. Ishibashi, Chem. Rev., 93, 1753 (1993).
M. Ishibashi, M. Takahashi, and J. Kobayashi, J. Org. Chem., 60,
6062 (1995).
4
T. K. Chakraborty and S. Dutta, J. Chem. Soc., Perkin Trans. 1,
1997, 1257.
5
6
B. B. Snider and J. V. Duncia, J. Org. Chem., 45, 3461 (1980).
(a) Y. Gao, R. M. Hanson, J. M. Klunder, S. Y. Ko, H. Masamune,
and K. B. Sharpless, J. Am. Chem. Soc., 109, 5765 (1987); (b) T.
Katsuki and V. S. Martin, Org. React., 48, 1 (1996); (c) Sharpless
kinetic resolution of a similar substrate is reported: A. R.
Chamberlin, M. Dezube, S. H. Reich, and D. J. Sall, J. Am. Chem.
Soc., 111, 6247 (1989); (d) Sharpless kinetic resolution of 18 was
done following standard procedure (ref. 6a-c) using Ti(iPrO)4 (0.1
eq.), (+)-DIPT (0.12 eq.) and TBHP (1.0 eq.) at – 20 °C. After 25
min., the reaction was quenched by adding an aqueous solution of
tartaric acid (30%) and after usual work-up, the residue was purified
by silica gel column chromatography to get the unreacted allylic
alcohol (52%), followed by the desired product 14 (43%). A small
amount of the syn diastereomer (ca. 2-3%) was also formed which
could be separated easily. While the diastereomeric purity of 14
carbon extension: oxidation, Wittig olefination and hydrobora-
tion, to give 22. PMB-protection of 22 was followed by desily-
lation and oxidation to furnish the desired fragment 4.10
Synthesis of 5 is described in Scheme 5. Oxidation of 6
was followed by Wittig methylenation to give the intermediate
23. Removal of the acetonide, disilylation, and then selective
deprotection of the primary hydroxyl gave alcohol 24. Swern
oxidation of 24 was followed by Horner-Wadsworth-Emmons
olefination with the ketophosphonate 2511 to furnish the E-
enone 26 with complete selectivity and no Z-olefin was detect-
1
was ascertained by H NMR spectroscopy, its ee (85%) was deter-
mined by Mosher’s ester method. Selected physical data for 14:
22
1
[α]D 2.8 (c 1.0, CHCl3); H NMR (CDCl3, 200 MHz): δ 7.4-7.25
(m, 5 H, ArH), 4.65 and 4.52 (ABq, 2 H, PhCH2O-), 3.75 (q, J = 6.7
Hz, 1 H, CH3CHOH), 3.68 (dd, J = 10.5, 4.5 Hz, 1 H, CH-O), 3.57
(dd, J = 10.5, 6 Hz, 1 H, CH'-O), 3.28 (dd, J = 6, 4.5 Hz, 1 H, epoxy
H), 2.05 (br s, 1 H, OH), 1.25 (s, 3 H, epoxy Me), 1.22 (d, J = 6.7
Hz, 3 H, CH3CHOH).
7
The stereochemistry of 15 and its minor diastereomer were deter-
mined, as described earlier (ref. 4), by converting them to 6-mem-
bered acetonides and studying their proton coupling constants (4-5
Hz for syn-protons and 8-9 Hz for anti-protons).
8
9
K. S. Kim, Y. S. Song, B. H. Lee, and C. S. Hahn, J. Org. Chem., 51,
404 (1986).
K. Ishihara, H. Kurihara, and H. Yamamoto, J. Org. Chem., 58, 3791
(1993).
10 Selected physical data for 4: 1H NMR (CDCl3, 200 MHz, amphidino-
lide numberings): δ 7.4 and 6.82 (two d, J = 8.5 Hz, 4 H, aromatic),
4.65 (s , 2 H, O-CH2-O), 4.38 (s, 2 H, O-CH2-Ar), 4.0 (m, 1 H, C3-
H), 3.8 (s, 3 H, PMB: -OMe), 3.65-3.45 (m, 6 H, O-CH2-CH2-O,
C1-H2), 3.35 (s, 3 H, MEM: -OMe), 2.86 (dq, J = 6.4 Hz, 1 H, C4-
H), 2.15 (s, 3 H, COCH3), 1.72 (m, 2 H, C2-H2), 1.05 (d, J = 6.4 Hz,
3 H, C4-CH3); MS (LSIMS): m/z 353 (M+-H), 377 (M++Na).
11 The ketophosphonate 25 was prepared in two steps from mono-ben-
zyl-protected propane-1,3-diol as follows: i) Jones’ oxidation –
CH2N2 (to give ester); ii) CH3P(O)(OCH3)2 – nBuLi (Li-phospho-
nate addition to the ester to give the ketophosphonate).
ed. Finally, Wittig methylenation converted the enone 26 to
the desired 1,3-diene intermediate 5.12
In conclusion, two major fragments of amphidinolides O
and P have been synthesized from a common chiral intermedi-
ate 6, which was obtained using a method developed by us
recently involving radical-mediated opening of a trisubstituted
epoxy alcohol, thus, demonstrating its practical utility. Further
work on the total synthesis is presently under progress.
12 Selected physical data for 5: 1H NMR (CDCl3, 200 MHz, amphidino-
lide numberings): δ 7.35 (m, 5 H, aromatic), 6.15 (d, J = 16.5 Hz, 1
H, C12-H), 5.62 (dd, J = 16.5, 7 Hz, 1 H, C13-H), 5.02 (two s, 2 H,
C11=CH2), 4.75 (two s , 2 H, C16=CH2), 4.55 (s, 2 H, OCH2Ph), 4.12
(t, J = 7 Hz, 1 H, C14-H), 3.62 (t, J = 7 Hz, 2 H, C9-H2), 2.55 (t, J =
7 Hz, 2 H, C10-H2), 2.28 (dq, J = 7 Hz, 1 H, C13-H), 1.75 (s, 3 H,
C16-CH3), 0.95 (d, J = 7 Hz, 3 H, C15-CH3), 0.9 (s, 9 H, SitBu), 0.05
and 0.0 (two s, 6 H, SiMe2); 13C NMR (CDCl3, 50 MHz): δ 147.2,
142.4, 138.5, 132.1, 131.2, 128.3, 127.8, 127.3, 118.5, 111.5, 76.2,
73, 69, 47.8, 32.7, 25.4, 21.8, 18.2, 14.5, -4.3, -4.8; MS (LSIMS):
m/z 399 (M+-H).
We thank Drs. A. C. Kunwar and M. Vairamani for NMR
and mass spectroscopic assistance, respectively; UGC, New
Delhi for research fellowship (S.D.) and Young Scientist
Award Research Grant (T.K.C.).
References and Notes
1
M. Ishibashi and J. Kobayashi, Heterocycles, 44, 543 (1997).