LETTER
Straightforward Synthesis of the Antibiotic Lissoclinolide
1289
Liebeskind, L. S., Ed.; JAI Press: Greenwich, Connecticut,
1996, 1. (c) Mitchell, T. N. Synthesis 1992, 803. (d) Farina,
V.; Krishnamurthy, V.; Scott, W. J. Org. React. 1997, 50, 1.
(e) Mitchell, T. N. In Metal-Catalyzed Cross-Coupling
Reactions, 2nd Ed.; de Meijere, A.; Diederich, F., Eds.;
Wiley-VCH: Weinheim, 2004, 125.
OH
O
O
O
O
O
OH
39
AcO
(9) (a) Brückner, R.; Siegel, K.; Sorg, A. In Strategies and
Tactics in Organic Synthesis, Vol. 5; Harmata, M., Ed.;
Elsevier: Amsterdam, 2004, 437. (b) Sorg, A.; Brückner, R.
Angew. Chem. Int. Ed. 2004, 43, 4523; Angew. Chem. 2004,
116, 4623. (c) Sorg, A.; Siegel, K.; Brückner, R. Chem.–
Eur. J. 2005, 11, 1610.
(10) Helberger, J. H.; Ulubay, S.; Civelekoglu, H. Liebigs Ann.
1949, 215.
(11) Grundmann, C.; Kober, E. J. Am. Chem. Soc. 1955, 77,
2332.
Br
O
Br
Z-8
OH
O
(12) Synthetic sequence 22ꢀ23ꢀ25: Ochoa de Echagüen, C.;
Ortuño, R. M. Tetrahedron 1994, 50, 12457.
(13) Compound 24 resulted from an initial 1:1-addition, rather
than 2:1-addition of bromine to protoanemonin (2).
(14) Still, W. C.; Kahn, M.; Mitra, A. J. Org. Chem. 1978, 43,
2923.
O
40
AcO
Scheme 8
In conclusion, we have presented a powerful new strategy
for the stereoselective synthesis of Z-configured a-alke-
nyl-g-alkylidenebutenolides. The transformation Z-
8→36→37 (Scheme 6) models specifically how sequen-
tial Stille couplings between Z-8 and more complex alke-
nylstannanes than 34/35 should develop into novel and
concise approaches to totally synthetic specimens of peri-
dinin (3933) and pyrrhoxanthin (4034), key carotenoids for
marine photosynthesis (Scheme 8).
(15) All new compounds except 23 gave satisfactory 1H and 13
NMR spectra and provided either correct combustion
analyses or HRMS.
C
(16) (Z)-3-Bromo-5-(bromomethylene)-2(5H)-furanone( Z-8):
Et3N (0.46 mL, 0.34 g, 3.3 mmol, 1.1 equiv) was added
dropwise at –78 °C to a solution of 3,5-dibromo-5-
(bromomethyl)-2(5H)-furanone (25) (1.002 g, 2.993 mmol)
and hydroquinone (a few crystals) in CH2Cl2 (5 mL). The
mixture was allowed to warm to 0 °C where it darkened
gradually. After 1 h and without aqueous work-up,
purification by flash chromatography on silica gel
(cyclohexane–EtOAc, 10:1→5:1) furnished the title
compound (0.5826 g, 78%) as a colorless solid (mp 72–
73 °C). 1H NMR (300.1 MHz, CDCl3/TMS): d = 6.19 (s, 1¢-
H), 7.49 (s, 4-H). 13C NMR (125.7 MHz, CDCl3/CHCl3):
d = 93.17 (C-1¢), 114.53 (C-3), 139.36 (C-4), 150.85 (C-5),
163.97 (C-2). Anal. calcd for C5H2Br2O2 (251.8): C 23.65;
H 0.79. Found: C 23.67; H 0.51.
Acknowledgment
We are grateful to the Fonds der Chemischen Industrie for general
financial support.
References
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(19) Prepared by a procedure analogous to: Gilman, H.;
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(24) The reaction of Z-8 with 35 under the hitherto used
conditions [Pd(dba)2, AsPh3, CuI] was troublesome, leading
to inseparable isomeric mixtures of 36 with up to 15% of its
1¢-E-isomer. Running the same reaction in the absence of
CuI increased the Z:E-ratio to 94:6.
Synlett 2005, No. 8, 1286–1290 © Thieme Stuttgart · New York