2088
A. L. Lawrence et al.
LETTER
of the conjugated enolate of trienone 5 may possibly facil-
itate the 8p–6p electrocyclization cascade, in an analo-
gous manner to the anionic oxy-Cope rearrangement.11
a
b, c
MeO2C
MeO2C
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Use of DBU in benzene on model system 6 only led to
double bond migration,4 so it was decided to deprotonate
trienone 5 irreversibly using a strong base, and prelimi-
nary results for the electrocyclization are promising
(Table 1).
12
13
d, e
O
CO2Me
CO2Me
f
CO2Me
Table 1 Preliminary Results of the Electrocyclization of Trienone 5
OPMB
14
OPMB
H
15
Scheme 2 Reagents and conditions: (a) 180 °C, excess butadiene,
hydroquinone (5 mol%), 92%; (b) LiAlH4, THF, 0 °C, 89%; (c)
PMBCl, NaH, cat. t-Bu4NI, THF, reflux, 100%; (d) OsO4, Oxone,
DMF, r.t.; (e) MeI, K2CO3, DMF, r.t., 74% over two steps; (f) KOt-
Bu, THF, r.t., 99%.
O
O
OPMB
OPMB
5
20
Solvent
Base (equiv)
none
Temp (°C) Time (h) Yield (%)a
ter screening many conditions, including various Stille re-
actions, it was found that a simple Negishi reaction
provided diene-ester 17 in 82% yield (Scheme 3).8 Reduc-
tion of ester 17 to aldehyde 18 was achieved via DIBAL-
H reduction followed by MnO2 oxidation. Zinc-mediated
crotylation9 of 18 and final IBX oxidation10 provided
trienone 5 in 73% overall yield for the four steps, on a
gram scale and with just one final chromatographic puri-
fication required (Scheme 3).
DMSO
DME
DME
150
85
80
20
12
16
22
47
NaH (1.5)
NaHMDS (1.5)
85
a Isolated yield; mixture of isomers.
Further work investigating the anionic electrocyclic ring
closure of trienones, using our previous model systems 6–
8, and elaboration of enone 20 to form natural sesquiter-
penes, for example 1–3, is currently underway and will be
reported in due course.
OTf
O
O
a
b
CO2Me
CO2Me
OMe
References and Notes
OPMB
OPMB
OPMB
(1) (a) Starrat, A. N.; Ward, E. W. B.; Stothers, J. B. Can. J.
Chem. 1989, 67, 417. (b) Starrat, A. N.; Ward, E. W. B.;
Stothers, J. B. J. Chem. Soc., Chem. Commun. 1988, 9, 590.
(2) Fabian, K.; Lorenzen, K.; Anke, T.; Johansson, M.; Sterner,
O. Z. Naturforsch., C: Biosci. 1998, 53, 939.
(3) Abraham, W. R. Curr. Med. Chem. 2001, 8, 583.
(4) Lawrence, A. L.; Wegner, H. A.; Jacobsen, M. F.;
Adlington, R. M.; Baldwin, J. E. Tetrahedron Lett. 2006, 47,
8717.
16
17
15
c, d
e
f
O
OH
O
OPMB
18
OPMB
OPMB
19
(5) Travis, B. R.; Narayan, R. S.; Borhan, B. J. Am. Chem. Soc.
2001, 124, 3824.
5
(6) (a) Peelen, T. J.; Chi, Y.; English, E. P.; Gellman, S. H. Org.
Lett. 2004, 6, 4411. (b) It should be noted that addition of
the diester to the basic solution had to be slow (≥ 4 h)
otherwise low yields of impure product were obtained.
(7) (a) Comins, D. L.; Dehghani, A. Tetrahedron Lett. 1992, 42,
6299. (b) Comins, D. L.; Dehghani, A.; Foti, C. J.; Joseph,
S. P. Org. Synth. 1997, 74, 77.
Scheme 3 Reagents and conditions: (a) Comins reagent, NaH,
THF, r.t., 95%; (b) 2-bromopropene, t-BuLi, ZnCl2, Pd(PPh3)4, THF,
–78 °C to r.t., 82%; (c) DIBAL-H, Et2O, –78 °C; (d) MnO2, CH2Cl2,
r.t.; (e) Zn, crotyl bromide, aq NH4Cl–THF (1:2), 0 °C; (f) IBX,
DMSO, r.t., 73% over four steps.
(8) General procedure for Pd-catalyzed Negishi coupling taken
from: Milne, J. E.; Buchwald, S. L. J. Am. Chem. Soc. 2004,
126, 13028.
(9) Luche, J. L.; Petrier, C.; Einhorn, J. Tetrahedron Lett. 1985,
26, 1445.
(10) Frigerio, M.; Santagostino, M. Tetrahedron Lett. 1994, 35,
8019.
(11) Snider, B. B.; Harvey, T. C. J. Org. Chem. 1994, 59, 504.
Studies on the model trienones 6–8 had shown that simple
heating in polar solvents provided the tricyclic products
9–11 in moderate yields (Scheme 1).4 Upon heating
trienone 5 in DMSO at 150 °C, even for extended periods
of time resulted in a yield of 16% of enone 20 (Table 1).
It was therefore decided to explore the idea that formation
Synlett 2008, No. 14, 2087–2088 © Thieme Stuttgart · New York