LETTER
Alkene Chemoselectivity in Ring-Closing Metathesis: A Formal Synthesis of (-)-Periplanone-B
745
tane) gave the sensitive dihydropyran 13 which was best References and Notes
converted directly into the aldehyde 14 (55% from triene
(
(
1) Hodgson, D. M.; Boulton, L. T.; Maw, G. N. Synlett 1995,
1
7
1
(
2). Elaboration of the aldehyde 14 to the substituted
267-268.
i
-)-dienone 1 (R = Pr ) {93% ee by chiral HPLC analy-
2) Schreiber, S. L.; Santini, C. J. Am. Chem. Soc. 1984, 106,
4038-4039. For a recent review on the synthesis of
germacrane sesquiterpenes and related compounds see:
Minnaard, A. J.; Wijnberg, J. P. B. A.; de Groot, A.
Tetrahedron 1999, 55, 2115-2146.
1
8
2
5
4
2
5
sis, [a] -310 (c 1.22 in hexane), lit. [a] -362 (c 1.22
D
D
1
in hexane)} followed our earlier chemistry, with the
exception that the stannane 15 was prepared from the
aldehyde 14 using our recently improved procedure.19
(
(
(
3) Schreiber, S. L.; Hawley, R. C. Tetrahedron Lett. 1985, 26,
5
971-5974.
4) Kitahara, T.; Mori, M.; Mori, K. Tetrahedron 1987, 43, 2689-
699.
5) Barber, C.; Jarowicki, K.; Kocienski, P. Synlett 1991, 197-
2
198; Crimmins, M. T.; O’Mahony, R. J. Org. Chem. 1989, 54,
1157-1161.
(
6) Fujimura, O.; Fu, G. C.; Grubbs, R. H. J. Org. Chem. 1994,
9, 4029-4031. Reviews: Schuster, M.; Blechert, S. Angew.
5
Chem. Int. Ed. Engl. 1997, 36, 2036-2056; Fürstner, A. Top.
Catal. 1997, 4, 285-299; Armstrong, S. K. J. Chem. Soc.,
Perkin 1 1998, 371-388; Grubbs, R. H.; Chang, S.
Tetrahedron 1998, 54, 4413-4450. Certain unsubstituted enol
ethers have recently been shown to undergo RCM using
(
PCy ) Cl Ru=CHPh: Sturino, C. F.; Wong, J. C. Y.
3 2 2
Tetrahedron Lett. 1998, 39, 9623-9626.
(7) Trienes 5 were prepared in three steps from commercially
available 5-hexynenitrile: (i) B-I-9-BBN then AcOH (75%)
(ref. 15); (ii) 4-pentenyl MgBr (n = 1, 60%), or 5-hexenyl
MgBr (n = 2, 58%); (iii) CH Br , TiCl , Zn, cat. PbCl (n = 1,
2
2
4
2
88%; n = 2, 92%) (ref. 16).
(
8) Reaction of triene 5 (n = 2) with (PCy ) Cl Ru=CHPh under
3
2
2
preferred conditions for RCM (ref. 10) resulted only in
dimerisation [44% (E : Z = 73 : 27), 61% based on recovered
triene] arising from metathesis at the the terminal (monoalkyl-
substituted) alkene. Very recently, Grubbs has reported an
imidazolinylidine-Ru catalyst which may be more effective:
Scholl, M.; Trnka, T. M.; Morgan, J. P.; Grubbs, R. H.
Tetrahedron Lett. 1999, 40, 2247-2250.
(
9) Isolated total yields of chromatographically homogeneous,
spectroscopically pure products are reported. All new
compounds were characterised by a full range of
1
13
Scheme 4
spectroscopic data, including H and C NMR and
microanalysis and/or high resolution mass spectrometry.
(
(
10) Kirkland, T. A.; Grubbs, R. H. J. Org. Chem. 1997, 62, 7310-
318.
7
In summary, we have demonstrated the tolerance of alk-
enyl halide functionality in RCM and used this chemo-
selectivity in a formal synthesis of (-)-periplanone-B. In
addition, our work suggests that tandem RCM-intramo-
lecular Heck reactions (using tethered alkenyl halide
11) Nicolaou, K. C.; He, Y.; Roschangar, F.; King, N. P.;
Vourloumis, D.; Li, T. Angew. Chem. Int. Ed. 1998, 37, 84-87.
See also footnote 18 in: Kim, S.-H.; Zuercher, W. J.; Bowden,
N. B.; Grubbs, R. H. J. Org. Chem. 1996, 61, 1073-1081.
12) Dale, J. A.; Dull, D. L.; Mosher, H. S. J. Org. Chem. 1969, 34,
2543-2549.
(
(
(
2
0
functionality) may be possible.
13) Evans, D. A.; Britton, T. C.; Dorow, R. L.; Dellaria, J. F., Jr.
Tetrahedron 1988, 44, 5525-5540.
Acknowledgement
14) Evans, D. A.; Britton, T. C.; Ellman, J. A. Tetrahedron Lett.
1
987, 28, 6141-6144; Gage, J. R.; Evans, D. A. Org. Synth.,
We thank SmithKline Beecham Pharmaceuticals and the EPSRC
for an Industrial CASE award (to A. M. F.), L. T. Boulton for preli-
minary studies, Prof. V. C. Gibson for initial assistance with RCM
of triene 12, Dr. J. Zukowski (SmithKline Beecham Pharmaceuti-
cals) for expert HPLC analysis and the EPSRC National Mass Spec-
trometry Service Centre for mass spectra.
Col. Vol. VIII, 1993, 339-343.
(
15) Hara, S.; Dojo, H.; Takinami, S.; Suzuki, A. Tetrahedron Lett.
1983, 24, 731-734.
(
16) Takai, K.; Kakiuchi, T.; Kataoka, Y.; Utimoto, K. J. Org.
Chem. 1994, 59, 2668-2670; Takai, K.; Kataoka, Y.; Miyai, J.;
Okazoe, T.; Oshima, K.; Utimoto, K. Org. Synth. 1995, 73,
73-84.
(17) Preparation of (2S)-2-(1-methylethyl)-9-iodo-5-oxo-9-
decenal 14: A solution of triene 12 (0.758 g, 2.18 mmol) in
3
dry, degassed pentane (40 cm ) was added dropwise to a
stirred solution of 2,6-diisopropylphenylimidoneophylidene
molybdenum bis(hexafluoro-t-butoxide) [(Strem), 0.200 g,
3
0
.26 mmol] in dry, degassed pentane (180 cm ) at 25 °C under
Synlett 1999, No. 6, 744–746 ISSN 0936-5214 © Thieme Stuttgart · New York