LETTER
Total Synthesis of (–)-Chokol A
2225
O
O
10a
OMe
72%
methanolysis
O
O
OBn
MeOH, 120° C
(in a sealed tube)
OR1
11
– R*OH
OR2
retro-
O
Dieckmann
MeO
10b
OMe
O
OTBDPS
65%
12
R2
Bn
OR1
compound
O
A
B
10a
= A
= B
N
TBDPS
10b
O
SO2Ph
Scheme 3
(5) (a) Oppolzer, W.; Cunningham, A. F. Tetrahedron Lett.
1986, 27, 5467. (b) Lawler, D. M.; Simpkins, N. S.
Tetrahedron Lett. 1988, 29, 1207. (c) Tanimori, S.; Ueda,
T.; Nakayama, M. Biosci. Biotechnol. Biochem. 1994, 58,
1174. (d) Groth, U.; Halfbrodt, W.; Köhler, T.; Kreye, P.
Liebigs Ann. Chem. 1994, 9, 885. (e) Deloux, L.; Srebnik,
M. Tetrahedron Lett. 1996, 37, 2735.
chromatography we isolated the natural product (–)-
chokol A in 74% yield and the enantiomeric excess was
determined to be ≥95% by comparing its optical rotation
20
{[a]D –56.2 (c 0.58, EtOH)} with the data reported
earlier.6
(6) (a) Mash, E. A. J. Org. Chem. 1987, 52, 4142. (b) Suzuki,
T.; Sato, E.; Matsuda, Y.; Tada, H.; Koizumi, S.; Unno, K.;
Kametami, T. J. Chem. Soc., Chem. Commun. 1988, 1531.
(c) Suzuki, T.; Tada, H.; Unno, K. J. Chem. Soc., Perkins
Trans. 1 1992, 2017. (d) Urban, E.; Knühl, G.; Helmchen,
G. Tetrahedron 1995, 51, 13031. (e) For the enantio-
selective synthesis of (–)-chokol G, see: Kanada, R. M.;
Tanaguchi, T.; Ogasawara, K. Chem. Commun. 1998, 1755.
(7) Groth, U.; Halfbrodt, W.; Kalogerakis, A.; Köhler, T.;
Kreye, P. Synlett 2004, 291.
(8) For recent reviews on domino reactions, see: (a) Tietze, L.
F. J. Heterocycl. Chem. 1990, 27, 47. (b) Tietze, L. F.;
Beifuss, U. Angew. Chem., Int. Ed. Engl. 1993, 32, 131;
Angew. Chem. 1993, 105, 137. (c) Tietze, L. F.; Bachmann,
J.; Wichmann, J.; Burkhardt, O. Synthesis 1994, 1185.
(d) Tietze, L. F. Chem. Ind. (London, U.K.) 1995, 453.
(e) Tietze, L. F. Chem. Rev. 1996, 96, 115. (f) Tietze, L. F.;
Modi, A. Med. Res. Rev. 2000, 20, 304. (g) Tietze, L. F.;
Haunert, F. Domino Reactions in Organic Synthesis. An
Approach to Efficiency, Elegance, Ecological Benefit,
Economic Advantage and Preservation of our Resources in
Chemical Transformations, In Stimulating Concepts in
Chemistry; Shibasaki, M.; Stoddart, J. F.; Vögtle, F., Eds.;
Wiley-VCH: Weinheim, 2000, 39–64. (h) Tietze, L. F.;
Rackelmann, N. Pure Appl. Chem. 2004, 76, 1967.
(i) Tietze, L. F.; Brasche, G.; Gericke, K. Domino Reactions
in Organic Synthesis; Wiley-VCH: Weinheim, 2006.
(9) For the synthesis of 2-bromo-5-hydroxypent-2-ene 7, see
also: Lawler, D. M.; Simpkins, N. S. Tetrahedron Lett. 1988,
29, 1207.
Acknowledgment
The authors are grateful to Metallgesellschaft AG and Wacker AG
for providing valuable starting materials. P.K. thanks the Cusanus-
Werk – Bischöfliche Hochbegabtenförderung – for a doctoral
fellowship.
References and Notes
(1) (a) Stereoselective Synthesis of Steroids and Related
Compounds, IX. For part VIII, see: Groth, U.; Kalogerakis,
A.; Richter, N. Synlett 2006, 905. (b) Lanthanides in
Organic Synthesis, part VI. For part V, see: Groth, U.;
Kesenheimer, C.; Neidhöfer, J. Synlett 2006, 12, 1859.
(2) Koshino, H.; Yoshihara, T.; Togiya, S.; Terada, S.; Tsukada,
S.; Okuno, M.; Noguchi, A.; Sakamura, S.; Ichihara, A.
Tennen Yuki Kagobutsu Toronkai Koen Yoshishu 1989, 31,
244.
(3) Yoshihara, T.; Togiya, S.; Koshino, H.; Sakamura, S.;
Shimanuki, T.; Sato, T.; Tajimi, A. Tetrahedron Lett. 1985,
26, 5551.
(4) Sakamura, S. In Biologically Active Natural Products –
Potential Use in Agriculture; Culter, H. G., Ed.; ACS
Symposium Series, Vol. 380, Oxford University Press: New
York, 1988.
Synlett 2006, No. 14, 2223–2226 © Thieme Stuttgart · New York