G. Mehta, J. Nandakumar / Tetrahedron Letters 43 (2002) 699–702
701
c
HO
HO
a
d
b
(+)-2
O
OH
9a
(+)-8
9b
10
Scheme 4. Reagents and conditions: (a) 5-bromo-1-pentene, Li, sonication, 80% (b) Ru[(PCy3)2Cl2CHPh] (30 mol%), CH2Cl2, 40°C
(c) silica gel, 9a 8%, 9b 62% (d) TPAP, NMMO, CH2Cl2, rt, 56%.
It was considered appropriate to probe the generality of
this novel tandem metathesis reaction. For this pur-
pose, a Barbier reaction was performed on (+)-2 with
5-bromopentene in the presence of lithium metal to
afford the tertiary alcohol (+)-8 in good yield (Scheme
4). The resulting triene alcohol was exposed to Grubbs’
catalyst under conditions identical to those employed
for (+)-3.7 In an analogous manner, (+)-8 also furnished
one major product 9a, which converted to 9b8 during
purification on a silica gel pad. On oxidation with
TPAP,9 9a,b afforded the enone 107 whose structure
2. Mehta, G.; Nandakumar, J. Tetrahedron Lett. 2001, 42,
7667.
3. For a recent review on taxoids, see: Mehta, G.; Singh, V.
K. Chem. Rev. 1999, 99, 881.
4. A related approach from b-pinene to the AB rings of
taxoids has been reported: Wenz, M.; Grossbach, D.;
Beitzel, M.; Blechert, S. Synthesis 1999, 607.
5. Recent reviews: (a) Schuster, M.; Blechert, S. Angew.
Chem., Int. Ed. Engl. 1997, 36, 2036; (b) Grubbs, R. H.;
Chang, S. Tetrahedron 1998, 54, 4413.
6. (a) Schwab, P.; Grubbs, R. H.; Ziller, J. W. J. Am. Chem.
Soc. 1996, 118, 100; (b) Zuercher, W. J.; Hashimoto, M.;
Grubbs, R. H. J. Am. Chem. Soc. 1996, 118, 6634; (c)
Bassindale, M. J.; Edwards, A. S.; Hamley, P.; Adams, H.;
Harrity, J. P. A. Chem. Commun. 2000, 1035; (d) Bassin-
dale, M. J.; Hamley, P.; Leitner, A.; Harrity, J. P. A.
Tetrahedron Lett. 1999, 40, 3247.
7. Experimental procedure for the tandem ring-closing/ring-
opening metathesis reaction of (+)-3 and (+)-8: To a
solution of the substrate (+)-3 (0.045 mmol) in degassed
DCM (7 ml) was added dropwise a solution of Grubbs’
catalyst (30 mol%) in degassed DCM (3 ml) under an
argon atmosphere. The resultant solution was refluxed for
2 h. The solvent was evaporated in vacuo and the residue
was loaded on a pad of silica gel. Elution with 1% EtOAc–
hexane afforded the less polar product 6a (6%). Further
elution with 5% EtOAc–hexane furnished the more polar
product 6b (63%). Reaction of (+)-8 with Grubbs’ catalyst
under identical conditions led to 9a (8%) and 9b (62%)
after chromatography on silica gel. Procedure for the
TPAP/NMMO oxidation of 6b and 9b: To a solution of
the allylic alcohol 6b or 9b (0.007 mmol) in DCM (3 ml)
was added NMMO (10 mg, 0.09 mmol) and a pinch of
TPAP. The solution was stirred at room temperature for 1
h, diluted with DCM, washed with brine and dried over
Na2SO4 and concentrated. The crude product was passed
through a pad of silica gel and eluted with 5% EtOAc–hex-
ane to afford the enone 7 (61%) or 10 (56%).
1
was deduced with the help of H, 13C NMR, IR and
MS data8 which clearly indicated the presence of the
cyclohexenone moiety rather than the cyclopentenone
moiety (Scheme 4). The symmetry element associated
with the formulation 10 was clearly discernible. Struc-
tural assignment of 10, in turn led to the unambiguous
formulation of 9a and 9b. Mechanistically 9a can be
derived from (+)-8 in a manner similar to that depicted
in Scheme 3.
In summary, we have observed interesting tandem ring-
opening/ring-closing metathesis reactions in function-
ally embellished cyclohexene derivatives in the presence
of the Grubbs’ catalyst. Such reactions could be
employed in a very facile manner, even in a relatively
strain-free carbocyclic ring such as the cyclohexenyl
ring, to obtain interesting products through deep-seated
structural change.
Acknowledgements
We would like to thank the SIF at IISc for providing
high field NMR data.
8. All new compounds reported here were duly characterized
on the basis of spectral [IR, 1H (2D wherever required)
1
and 13C NMR and MS data] Selected spectral data: 6b: H
References
NMR (300 MHz, CDCl3): l 5.62 (2H, s), 5.49 (1H, dd,
J=3.5, 1.8 Hz), 4.81 (1H, m), 2.54–2.04 (7H, series of m),
1.73–1.64 (2H, m), 1.00 (3H, s), 0.99 (3H, s); 13C NMR (75
MHz, CDCl3): l 157.6, 129.93, 129.89, 125.5, 77.6, 44.9,
38.2, 34.2, 34.1, 29.8, 28.4, 23.79, 23.77. 7: IR (neat): 1705
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1
cm−1; H NMR (300 MHz, CDCl3): l 5.97 (1H, t, J=1.7
Hz), 5.65 (2H, m), 2.67–2.63 (2H, m), 2.60–2.49 (1H, m),
2.43–2.40 (2H, m), 2.37–2.28 (2H, m), 2.15–2.08 (2H, m),
1.11 (6H, s); 13C NMR (75 MHz, CDCl3): l 210.5, 190.3,
129.8 (2C), 128.8, 45.1, 40.8, 35.3, 34.3 (2C), 28.0, 23.6