COMMUNICATIONS
CH(TMS)), 0.42 (s, 9H; TMS-benzyl), 0.59 (s, 9H; TMS-fluorenyl), 0.95
(mb, 4H; THF), 1.93 and 1.96 (2 s, 6H; NMe2), 2.59 (mb, 4H; THF), 6.12
(t, 3J(H,H) 7.5 Hz, 1H; benzyl), 6.27 (d, 3J(H,H) 7.8 Hz, 1H; benzyl),
6.31 (t, 3J(H,H) 7.5 Hz, 1H; benzyl), 6.88 (d, 3J(H,H) 8.4 Hz, 1H;
benzyl), 7.04 (t, 3J(H,H) 7.5 Hz, 1H; fluorenyl), 7.09 (t, 3J(H,H) 7.5 Hz,
1H; fluorenyl), 7.24 (t, 3J(H,H) 7.2 Hz, 1H; fluorenyl), 7.31 (t, 3J(H,H)
7.5 Hz, 1H; fluorenyl), 7.93 (d, 3J(H,H) 7.8 Hz, 1H; fluorenyl), 8.03 (d,
3J(H,H) 8.4 Hz, 1H; fluorenyl), 8.14 (d, 3J(H,H) 8.4 Hz, 1H; fluoren-
ªBiomimeticº Cascade Reactions in Organic
Synthesis: Construction of 4-Oxatricyclo-
[4.3.1.0]decan-2-one Systems and Total
Synthesis of 1-O-Methylforbesione via Tandem
Claisen Rearrangement/Diels ± Alder
Reactions**
3
yl), 8.17 (d, J(H,H) 7.8 Hz, 1H; fluorenyl); 13C NMR (600 MHz, C6D6,
K. C. Nicolaou* and Jim Li
208C): d 2.43 (TMS), 2.44 (TMS), 24.9 (THF), 41.8 (NMe), 44.5 (NMe),
44.9 (CH(TMS)), 68.5 (THF), aromatics: 87.0, 112.8, 116.5, 116.8, 119.4,
121.2, 121.4, 121.7, 121.9, 123.3, 124.2, 124.3, 124.4, 126.4, 128.3, 135.0, 140.7,
140.9, 147.0.
The intriguing 4-oxatricyclo[4.3.1.0]decan-2-one ring sys-
tem is found in a growing class of biologically active natural
products isolated from the genus Garcinia of the Guttiferae
family of plants. Among the members of this class of
compounds are forbesione (2, isolated from Garcinia forbe-
sii),[1] morellin (3, from G. morella),[2] and the cytotoxic agents
Crystal structure determination of 3: Crystals grown from benzene solution
contain up to three equivalents of benzene per Ca atom and crack upon
cooling resulting in broad peak profiles and poor diffraction. Crystals
grown from warm hexane also show solvent incorporation but remain
stable upon cooling. Measurement on an Enraf Nonius CAD4 diffractom-
eter at 908C, MoKa, 2qmax 508, 13501 independent reflections (Rint
0.011), 10658 reflections observed with I > 2s(I). Crystal data: C32H45Ca-
O
H
Å
NOSi2 triclinic, space group P1, a 13.5981(13), b 16.8236(12), c
18.2031(15) ,
a 70.779(6),
b 77.084(7),
g 82.671(7)8,
V
3826.1(6) 3, Z 4, R 0.0456, wR2 0.1466, GOF 1.08, 1max
O
OH
O
O
O
OR
O
O
1
0.57 e 3, 1min
0.44 e 3. The unit cell contains a hole with two
2
3
severely disordered hexane molecules (confirmed by NMR analysis).
Disorder was treated with the bypass method using the program
SQUEEZE[17] incorporated in PLATON.[18] Crystallographic data (exclud-
ing structure factors) for the structure reported in this paper have been
deposited with the Cambridge Crystallographic Data Centre as supple-
mentary publication no. CCDC-165023. Copies of the data can be obtained
free of charge on application to CCDC, 12 Union Road, Cambridge
CB21EZ, UK (fax: (44)1223-336-033; e-mail: deposit@ccdc.cam.ac.uk).
O
O
O
HO
4
1: R = Me: 1-O-methylforbesione
2: R = H: forbesione
3: morellin
Received: July 4, 2001 [Z17423]
OR
O
O
O
OMe O
O
O
[1] K. Knoll in Kunststoff Handbuch 4: Polystyrol (Eds.: H. Gausepohl,
R. Gellert), Hanser, München, 1996, pp. 67 ± 82; J. R. Wünsch in
Kunststoff Handbuch 4: Polystyrol (Eds.: H. Gausepohl, R. Gellert),
Hanser, München, 1996, pp. 82 ± 104.
O
O
HO
HO
[2] H. H. Brintzinger, D. Fischer, R. Mülhaupt, B. Rieger, R. M. Way-
mouth, Angew. Chem. 1995, 107, 1255; Angew. Chem. Int. Ed. Engl.
1995, 34, 1134; G. W. Coates, Chem. Rev. 2000, 100, 1223; L. Resconi,
L. Cavallo, A. Fait, F. Piemontesi, Chem. Rev. 2000, 100, 1253.
[3] G. Natta, P. Pino, P. Corradini, F. Danusso, E. Mantica, G. Mazzanti, G.
Moraglio, J. Am. Chem. Soc. 1955, 77, 1708.
[4] N. Ishihara, M. Kuramoto, M. Uoi, Macromolecules 1986, 21, 2464.
[5] M. Malanga, Adv. Mater. 2000, 12, 1869.
[6] R. J. Kern, Nature 1960, 187, 410.
[7] D. J. Worsfold, S. Bywater, Makromol. Chem. 1963, 65, 245.
[8] L. Cazzaniga, R. E. Cohen, Macromolecules 1989, 22, 4125.
[9] T. Makino, T. E. Hogen-Esch, Macromolecules 1999, 32, 5712.
[10] M. Kawabe, M. Murata, K. Soga, Macromol. Rapid Commun. 1999,
20, 569.
[11] C. Lambert, P. v. R. Schleyer, Angew. Chem. 1994, 106, 1187; Angew.
Chem. Int. Ed. Engl. 1994, 33, 1129.
[12] A. Weeber, S. Harder, H. H. Brintzinger, K. Knoll, Organometallics
2000, 19, 1325.
[13] S. Harder, F. Feil, A. Weeber, Organometallics 2001, 20, 1044.
[14] Circa 4 ± 5 equivalents result in fast inversion at room temperature.
Addition of larger amounts of THF result in the crystallization of the
solvent-separated ion pair: [Me3Si-fluorenyl ]2[Ca2(THF)6].
[15] Polymerizations with the analogue but more reactive strontium
complex show faster initiation and consequently less tailing (poly-
dispersity (P.D.) 1.218): F. Feil, S. Harder, Organometallics 2001,
accepted.
[16] Intramolecular chelation enhances the stability of carbanionic stereo-
genic centers: C. Strohmann, B. C. Abele, D. Schildbach, K. Stroh-
feldt, Chem. Commun. 2000, 865.
[17] P. A. van der Sluis, A. L. Spek, Acta Crystallogr. Sect. A 1990, 46, 194.
[18] A. L. Spek, PLATON, A Multipurpose Crystallographic Tool, Utrecht
University, Utrecht, The Netherlands, 2000.
6: 1-O-methylneobractatin
4: R = H: bractatin
5: R = Me: 1-O-methylbractatin
bractatin (4), 1-O-methylisobractatin (5), and 1-O-methyl-
neobractatin (6), all of which were found in the species G.
bracteata,[3] as well as lateriflorone (from G. lateriflora),[4]
[*] Prof. Dr. K. C. Nicolaou, J. Li
Department of Chemistry and The Skaggs Institute for Chemical
Biology
The Scripps Research Institute
10550 North Torrey Pines Road, La Jolla, CA 92037 (USA)
Fax : (1)858-784-2469
and
Department of Chemistry and Biochemistry
University of California, San Diego
9500 Gilman Drive, La Jolla, CA 92093 (USA)
[**] We thank Drs. D. H. Huang, G. Siuzdak, and R. Chadha for NMR
spectroscopic, mass spectrometric, and X-ray crystallographic assis-
tance, respectively. This work was financially supported by the
National Institutes of Health (USA), The Skaggs Institute for
Chemical Biology, a graduate fellowship from The Skaggs Institute
for Research (to J.L.), and grants from Abbott Laboratories,
ArrayBiopharma, Boehringer Ingelheim, DuPont, Hoffmann-La-
Roche, Merck, Pfizer, and Schering Plough.
Supporting information for this article is available on the WWW under
4264
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1433-7851/01/4022-4264 $ 17.50+.50/0
Angew. Chem. Int. Ed. 2001, 40, No. 22