LETTER
Synthesis of the C1-C11 Segment of Tedanolide
2009
TES
O
OH OTBS
OPMB
O
OH
O
OTBS
OPMB
a, b
MeO
MeO
OH
13
16
c, d
TES
TES
OTBS
O
OMe O
OTBS
O
O
OMe O
OPMB
MeO
TBSO
MeO
TBSO
4
17
Scheme 4 Reagents and conditions: Synthesis of 16: a) TESOTf, 2,6-lutidine, CH2Cl2, 93%; b) AD-mix- , t-BuOH-H2O, 88% (94% de);
c) TBSCl, imidazole, DMF, 91%; d) MeOTf, 2,6-di-t-butylpyridine, CHCl3, 60%.
Chem. Pharm. Bull. 1998, 46, 1335. (c) Liu, J.-F.; Abiko,
In optimization studies for this pivotal reaction, when al-
dehyde 11 was treated with 2 equivalents of ketene acetal
12 using 1 equivalent of TPPB and 1 equivalent of isopro-
panol in diethyl ether, only aldol product 13 was isolated.
(Scheme 2).8 As before, its stereochemistry was assigned
unambiguously using 13C NMR data. A stoichiometric
amount of alcohol is necessary in order to trap reactive sil-
icon species liberated in the course of the reaction. It is
known that these R3Si+ species can catalyze aldol reac-
tions albeit with little or no stereocontrol. Failure to
quench them leads to the formation of isomer 14b. Inter-
estingly, use of BF3 OEt2 as sterically less demanding
Lewis acid exclusively alkylates the ketene acetal at the -
position.
A.; Pei, Z.; Buske, D. C.; Masamune, S. Tetrahedron Lett.
1998, 39, 1873. (d) Taylor, R. E.; Ciavarri, J. P.; Hearn, B.
R. Tetrahedron Lett. 1998, 39, 9361. (e) Roush, W. R.;
Lane, G. C. Org. Lett. 1999, 1, 95. (f) Matsushima, T.;
Mori, M.; Zheng, B.-Z.; Maeda, H.; Nakajima, N.; Uenishi,
J.; Yonemitsu, O. Chem. Pharm. Bull. 1999, 47, 308.
(g) Jung, M. E.; Karama, U.; Marquez, R. J. Org. Chem.
1999, 64, 663. (h) Matsushima, T.; Zheng, B.-Z.; Maeda,
H.; Nakajima, N.; Uenishi, J.; Yonemitsu, O. Synlett 1999,
780. (i) Smith, A. B. III; Lodise, S. A. Org. Lett. 1999, 1,
1249. (j) Zheng, B.-Z.; Maeda, H.; Mori, M.; Kusaka, S.-I.;
Yonemitsu, O.; Matsushima, T.; Nakajima, N.; Uenishi, J.
Chem. Pharm. Bull. 1999, 47, 1288. (k) Jung, M. E.;
Marquez, R. Tetrahedron Lett. 1999, 40, 3129.
(l) Matsushima, T.; Nakajima, N.; Zheng, B.-Z.; Yonemitsu,
O. Chem. Pharm. Bull. 2000, 48, 855. (m) Zheng, B.-Z.;
Yamauchi, M.; Dei, H.; Kusaka, S.-I.; Matsui, K.;
Yonemitsu, O. Tetrahedron Lett. 2000, 41, 6441.
(n) Zheng, B.-Z.; Yamauchi, H.; Dei, H.; Yonemitsu, O.
Chem. Pharm. Bull. 2000, 48, 1761. (o) Jung, M. E.;
Marquez, R. Org. Lett. 2000, 2, 1669. (p) Jung, M. E.; Lee,
C. P. Org. Lett. 2001, 3, 333. (q) Loh, T.-P.; Feng, L.-C.
Tetrahedron Lett. 2001, 42, 6001. (r) Loh, T.-P.; Feng, L.-
C. Tetrahedron Lett. 2001, 42, 3223. (s) Matsui, K.; Zheng,
B.-Z.; Kusaka, S.-I.; Kuroda, M.; Yoshimoto, K.; Yamada,
H.; Yonemitsu, O. Eur. J. Org. Chem. 2001, 3615.
(t) Hearn, B. R.; Ciavarri, J. P.; Taylor, R. E. Org. Lett. 2002,
4, 2953.
Continuing with the synthesis of tedanolide, the newly
generated secondary alcohol was TES-protected and sub-
sequent Sharpless dihydroxylation to 16 stereoselectively
established the remaining stereocenters of the all-syn
polyketide fragment (Scheme 4).3b,f The alcohol at C2
could be selectively protected as TBS-ether and the re-
maining hydroxyl group at C3 was transformed into the
methyl ether 17 using MeOTf and di-tert-butylpyridine
for the O-alkylation. These transformations completed the
synthesis of the C1–C11 segment in which 6 chiral centers
were selectively generated in 14 steps and 9.6% overall
yield. Additionally, the hydroxyl groups have been differ-
entially protected thus allowing for selective removal fol-
lowed by functional group transformations in the
endgame of the synthesis. Progress on the total synthesis
will be reported in due course.
(4) Roush, W. R.; Bannister, T. D.; Wendt, M. D.; Jablonowski,
J. A.; Scheidt, K. A. J. Org. Chem. 2002, 67, 4275.
(5) (a) Christmann, M.; Bhatt, U.; Quitschalle, M.; Claus, E.;
Kalesse, M. Angew. Chem. Int. Ed. 2000, 39, 4364; Angew.
Chem. 2000, 112, 4535. (b) Christmann, M.; Bhatt, U.;
Quitschalle, M.; Claus, E.; Kalesse, M. J. Org. Chem. 2001,
66, 1885.
(6) (a) Christmann, M.; Kalesse, M. Tetrahedron Lett. 2001, 42,
1269. (b) Hassfeld, J.; Christmann, M.; Kalesse, M. Org.
Lett. 2001, 3, 3561. (c) Hassfeld, J.; Kalesse, M.
Tetrahedron Lett. 2002, 43, 5093.
(7) Hoffmann, R. W.; Weidmann, U. Chem. Ber. 1985, 118,
3980.
References
(1) Tedanolide was isolated from Tedanis ignis: Schmitz, F. J.;
Gunasekera, S. P.; Yalamanchili, G.; Hossain, M. B.; van der
Helm, D. J. Am. Chem. Soc. 1984, 106, 7251.
(2) 13-Deoxytedanolide was isolated from Mycale adhaerens:
Fusetani, N.; Sugawara, T.; Matsunaga, S.; Hirota, H. J. Org.
Chem. 1991, 56, 4971.
(3) (a) Matsushima, T.; Horita, K.; Nakajima, N.; Yonemitsu, O.
Tetrahedron Lett. 1996, 37, 385. (b) Matsushima, T.; Mori,
M.; Nakajima, N.; Maeda, H.; Uenishi, J.; Yonemitsu, O.
(8) Aldehyde 11 (92 mg, 0.218 mmol) dissolved in diethyl ether
(2 mL) was cooled to –78 °C under an argon atmosphere.
Tris(pentafluorophenyl)borane (110 mg, 0.217 mmol) was
added and a mixture of ketene acetal 12 (100 mg, 0.438
mmol) and isopropyl alcohol (17 L, 0.24 mmol) dissolved
Synlett 2002, No. 12, 2007–2010 ISSN 0936-5214 © Thieme Stuttgart · New York