Tetrasubstituted allene ethers; synthesis and use in Nazarov reactions

Article abstract of DOI:10.1055/s-2004-815994

A method for the synthesis of tetrasubstituted allene ethers is described, making use of a reverse Brook rearrangement in the key step. The allene products have been used in the Nazarov cyclization reaction.

Full text of DOI:10.1055/s-2004-815994

786
SPECIAL TOPIC
Tetrasubstituted Allene Ethers; Synthesis and Use in Nazarov Reactions
T
etrasubstituted A
r
llene
E
a
thers; Synth
d
esis and
U
se
l
in Na
z
e
arov Reac
y
tions K. Tokeshi, Marcus A. Tius*
2545 The Mall, University of Hawaii, Honolulu, Hawaii 96822, USA
E-mail: tius@gold.chem.hawaii.edu
Received 29 January 2004
butyllithium. Minor modifications to Ohfune’s procedure
were found to be crucial to the success of the process. The
purity of the n-butyllithium was also important. Use of
aged solutions of n-butyllithium, presumed to contain ap-
preciable amounts of lithium hydroxide, resulted in ero-
sion of the yield of rearranged product. Best yields were
obtained when a freshly opened bottle of n-butyllithium
solution in hexanes was used. After addition of the silyl
chloride, the temperature of the solution was maintained
at –20 °C for 40 minutes, rather than –45 °C for 2 hours,
as described in Ohfune’s procedure.10 We found that the
rearrangement in the case of 5a and 5b was very slow at
–45 °C. The reaction was quenched with aq NaHCO3 at
–20 °C. These minor modifications of the published pro-
cedure led to reproducible high yields of 5a and 5b. Pro-
tection of the free hydroxyl group in 5a and 5b as the
methoxymethyl derivative led to 6a and 6b.
Abstract: A method for the synthesis of tetrasubstituted allene
ethers is described, making use of a reverse Brook rearrangement in
the key step. The allene products have been used in the Nazarov cy-
clization reaction.
Key words: allenes, Nazarov reactions, ethers, rearrangements,
alkynes, cyclizations
Allenes and other cumulenes are an attractive starting
points for synthesis, in large part because of the high reac-
tivity engendered by strain. In the case of allenes, the or-
thogonal p bonds also create an opportunity to exploit the
axial chirality of unsymmetrically substituted cas-
es.1Although many synthetic approaches to allenes have
been described,2,3 to date no completely general method
has been reported for the preparation of fully substituted
allene ethers (see 1, Scheme 1).4 Brandsma5 and others6
have demonstrated that exposure of propargyl ethers 2 to
strong base results in isomerization to allenyl ethers 3. In
the case in which R2 ≠ H, the reaction often leads to an
equilibrium mixture of propargyl and allene ethers.7 It is
possible to selectively deprotonate 3 at C1, and to trap the
resulting allenyl nucleophile with electrophiles in a highly
efficient process. If deprotonation at C1 in 3 is not possi-
ble, then deprotonation at C3 takes place upon exposure to
alkyllithium base.8 This process also leads to an allenyl
nucleophile that can be trapped at C3 with electrophiles,
resulting in a trisubstituted allenyl ether. In this communi-
cation we describe a more direct alternative process for
the preparation of allenyl ethers, and also some examples
of their use in the Nazarov reaction.9
MeO
TBS
O
OH
a-d
e
C
HO
C
TBS
C
C
C
C
R
R
R
5a R = n-C6H13
5b R = c-C6H11
6a R = n-C6H13
6b R = c-C6H11
4a R = n-C6H13
4b R = c-C6H11
98%
83%
92%
74%
Scheme 2 a) BuLi, THF, –78 °C; (b) TBSCl; (c) BuLi, –20 °C; (d)
aq NaHCO3; (e) MeOCH2Cl, i-Pr2NEt, CH2Cl2.
Exposure of 6a and 6b in THF solution at –78 °C to a
small excess of sec-butyllithium, followed by an electro-
phile, led to the results that are summarized in Table 1.
Product yields were good or excellent in all cases, and the
reaction was successful with diverse electrophiles, includ-
ing alkyl halides, ketones, amides and chlorosilanes. It
was important to use sec-butyllithium as the base; n-butyl-
lithium or tert-butyllithium led to mixtures of starting ma-
terial and allene product. All products were moderately
sensitive to acid, therefore reactions were quenched with
aq NaHCO3, and column chromatography on silica gel
was performed with triethylamine (1%) in the eluent. By
using these precautions, all allenes were stable to storage
for several weeks at 0 °C.
R1O
R2
R1O
1
base
R1O
C
•
3
R3
C
H
•
H
R2
R4
R2
2
3
1
Scheme 1
Our work makes use of the elegant reverse-Brook rear-
rangement that has been described by Ohfune and co-
workers (Scheme 2).10 Readily available propargyl alco-
hols 4a and 4b were converted to propargyl silanes 5a and
5b by sequential exposure to n-butyllithium, tert-bu-
tyldimethylsilyl chloride (TBSCl), followed by more n-
The next goal was to determine whether the tert-butyldi-
methylsilyl group of the tetrasubstituted allenes could be
exchanged for a proton. Treatment of tetrasubstituted al-
lenyl ethers 8a and 8b with TBAF (1 equiv) and solid
LiOH (1 equiv) in THF at room temperature led to the de-
sired products 16a and 16b in 82% and 87% yield, respec-
tively (Scheme 3). In the absence of LiOH, the
desilylation reaction was extremely sluggish, and required
ca. 8 equivalents TBAF to proceed to completion. In the
SYNTHESIS 2004, No. 5, pp 0786–0790
x
x
.
x
x
.2
0
0
4
Advanced online publication: 03.03.2004
DOI: 10.1055/s-2004-815994; Art ID: C00304SS.pdf
© Georg Thieme Verlag Stuttgart · New York

SPECIAL TOPIC
Tetrasubstituted Allene Ethers; Synthesis and Use in Nazarov Reactions
787
droxy-,12 a-amino-,13 or to an a-alkyl cyclopentenone.14
Scheme 4 summarizes the results of the reactions of 16a
and 16b with morpholino enamide 17. Conversion of each
allene to the a-lithio derivative, followed by addition of a
solution of amide 17 presumably (E/Z ca. 1:2, 72% yield)
and 18b (E/Z ca. 1:5, 58% yield) took place when the re-
action mixture was transferred via cannula into a solution
of anhyd FeCl3 in dichloromethane at room temperature.
Quenching the reaction by transferring the solution into
HCl in ethanol led to cyclic products 18a and 18b, but also
resulted in hydrolysis of the excess allene ether. Chro-
matographic separation of the resulting enal from the de-
sired product proved to be difficult; therefore FeCl3 was
the reagent of choice.
Table 1 Tetrasubstituted Allenyl Ethers
Yield (%)
Electrophile
EtOH
Product
R =
n-C6H13
R =
c-C6H11
7a 85
8a 96
7b 77
8b 86
9b 85
MeO
TBS
O
O
O
O
O
O
O
O
O
•
•
•
•
•
•
•
•
•
H
R
R
R
R
R
MeI
MeO
TBS
CH3
Br
MeO
TBS
H2C
CH2
O
O
MeO
O
HO
CH3
R
a-c
Ph
N
H
•
CH3
PhCH2Br
10a 98
11a 93
12a 61
13a 76
14a 93
15a 95
MeO
TBS
CH3
O
H3C
17
R
Ph
16a R = n-C6H13
16b R = c-C6H11
18a R = n-C6H13 72%
58%
Ph
18b R = c-C6H11
11b 54
12b 87
13b 61
14b 97
15b 97
O
MeO
TBS
Scheme 4 (a) BuLi (1.8 equiv), THF, –78 °C; (b) 17 (1 equiv); (c)
FeCl3, CH2Cl2.
O
Me
Ph
N
OMe
Ph
a-Aminocyclopentenones 20a and 20b were prepared in
68% (E–Z ca. 1:2) and 48% yield (E–Z ca. 1:5), respec-
tively, in a similar way from a-methylcinnamonitrile 19
(Scheme 5). After quenching the reaction and inducing
cyclization with FeCl3 in diethyl ether, workup led to a so-
lution of a-aminocyclopentenone product. Consistent
with our earlier obsevations,13 a-aminocyclopentenones
20a and 20b were labile, and underwent some decompo-
sition during storage.
3-pentanone
benzophenone
PhSSO2Ph
TIPSCl
MeO
TBS
OH
CH3
CH3
R
R
R
R
MeO
TBS
OH
Ph
Ph
MeO
TBS
SPh
O
MeO
O
H2N
H3C
CH3
R
CN
CH3
a-c
Ph
H
•
CH3
MeO
TBS
19
R
Ph
20a R = n-C6H13 64%
53%
TIPS
16a R = n-C6H13
16b R = c-C6H11
20b R = c-C6H11
Scheme 5 (a) BuLi (1.8 equiv), THF, –78 °C; (b) 19 (1.0 equiv); (c)
FeCl3, Et2O.
presence of 1 equivalent LiOH the reaction was complete
within 2 hours at room temperature. At the end of 2 hours,
the reaction mixture was completely homogeneous.
Scheme 5 summarizes the preparation of two a-alkyl cy-
clopentenones. In this case, the intermediate was tertiary
alcohol 22, which was isolated after workup and cyclized
in a second step with FeCl3 to give 23a and 23b in 69%
yield (E–Z ca. 1:1) and 64% yield (E–Z ca. 1:5), respec-
tively, for the two steps. For these reactions a small excess
of allene was used so as to consume enone 21 completely.
This was done because of the difficulty of separating ex-
cess 21 from the products. Whereas the chromatographic
separation of E and Z isomers in the case of 18a, 18b and
20a was straightforward by flash column chromatography
on silica gel, in the case of 20b, 23a and 23b this proved
not to be possible.
MeO
TBS
O
MeO
O
a
•
H
•
CH3
CH3
R
R
8a R = n-C6H13
8b R = c-C6H11
16a R = n-C6H13 82%
16b R = c-C6H11
87%
Scheme 3 (a) 1 equiv TBAF, 1 equiv LiOH (s), THF, r.t.
With a supply of allenyl ethers 16a and 16b in hand, we
set out to examine them in each of the three broad cate-
gories of the cyclopentannelation reaction.11 Depending
upon the electrophile that is chosen to react with 16a and
16b, the cyclopentannelation leads either to an a-hy-
An efficient general method for preparing tetrasubstituted
allene ethers has been demonstrated. The products have
Synthesis 2004, No. 5, 786–790 © Thieme Stuttgart · New York

788
B. K. Tokeshi, M. A. Tius
SPECIAL TOPIC
H, CH3), 0.96–0.86 (m, 3 H, CH3), 0.10 (s, 3 H, CH3), 0.07 (s, 3 H,
CH3).
13C NMR (75 MHz, CDCl3): d = 89.0, 81.2, 55.2, 31.6, 29.1, 28.8,
27.1 (3 C), 22.8, 19.3, 17.2, 14.3, –7.7, –8.4.
CH3
OH
MeO
O
O
OMe
H3C
a-b
c
H
•
CH3
•
R
MS (EI): m/z (%) = 73 (61), 75 (100), 197 (4), 211 (4), 254 (1).
HRMS: m/z calcd for C15H30OSi [M+]: 254.2066; found: 254.2052.
R
CH3
16a R = n-C6H13
16b R = c-C6H11
MeO
22a R = n-C6H13
22b R = c-C6H11
O
tert-Butyl-(1-methoxymethoxynon-2-ynyl)dimethylsilane (6a)
To a solution of alkynol 5a (7.2 g, 28.3 mmol) in CH2Cl2 (30 mL)
was added Hünig’s base (9.9 mL, 56.6 mmol). After cooling to
0 °C, chloromethyl methyl ether (3.7 mL, 48.7 mmol) was added
and the mixture was allowed to stir at r.t. for 2 h. The reaction mix-
ture was diluted with aq NaHCO3 and Et2O. The aq phase was ex-
tracted with Et2O, the combined organic extracts dried (MgSO4),
and the solvent was removed in vacuo. Column chromatography
(silica gel; 0.625% EtOAc–hexane) gave 6a.
CH3
R
H3C
O
CH3
21
H3C
CH3
MeO
23a R = n-C6H1369%
64%
23b R = c-C6H11
OMe
Scheme 6 (a) BuLi (1.05 equiv), THF, –78 °C; (b) 21 (0.5 equiv); (c)
FeCl3, CH2Cl2.
Yield: 7.8 g (44.8 mmol; 92%); pale yellow oil.
IR (film): 2950, 1460, 1250, 1140 cm–1.
1H NMR (300 MHz, CDCl3): d = 4.99 (d, 1 H, J = 6.3 Hz, OCH2O),
4.51 (d, 1 H, J = 6.3 Hz, OCH2O), 4.18 (t, 1 H, J = 2.4 Hz, CH),
3.50 (s, 3 H, OCH3), 2.21 (td, 2 H, J = 6.9, 2.4 Hz, CH2), 1.58–1.23
(m, 8 H, CH2), 0.99 (s, 9 H, CH3), 0.98–0.88 (m, 3 H, CH3), 0.09 (s,
3 H, CH3), 0.08 (s, 3 H, CH3).
been shown to be useful in all three categories of the cy-
clopentannelation reaction. Cyclopentenones 18a, 18b,
20a, 20b, 23a and 23b are the first examples of cyclopen-
tannelation products bearing a b,b-disubstituted exocyclic
double bond. We anticipate that propargyl silanes 5 can be
prepared asymmetrically, and further that conversion to
the allene ether can be done with control of absolute ste-
reochemistry. Chiral, non-racemic allene ethers are prom-
ising partners for a number of different annulation
reactions.
13C NMR (75 MHz, CDCl3): d = 94.7, 93.1, 78.0, 57.6, 55.9, 31.6,
29.1, 28.8, 27.1 (3 C), 25.9, 22.8, 19.3, 17.3, –7.5, –8.0.
MS (EI): m/z (%) = 73 (100), 89 (29), 115 (13), 149 (5), 253 (14)
298 (1).
HRMS: m/z calcd for C17H34O2Si [M+]: 298.2328; found: 298.2370.
1H NMR and 13CNMR spectra were recorded on either a Varian
Mercury Plus 300 operating at 300 MHz or 75 MHz, respectively or
on a Varian Unity Inova 500 operating at 500 MHz or 126 MHz, re-
spectively. Infrared spectra were recorded on a Perkin-Elmer IR
1430 spectrometer. Electron impact mass spectra were recorded on
a VG-70SE mass pectromter. TLC was performed on Sigma-Ald-
rich TLC plates, 250 µm, particle size 5–17 mm, pore size 60 A.
Flash chromatography was performed on Natland International
Corporation silica gel, 200–400 mesh. Anhdrous THF, Et2O,
CH2Cl2 were taken from a solvent purification system from Glass-
Countour (www.glascounter.com). Et3N and Hünig’s base were
distilled from CaH2 and stored over KOH. Other reagents were used
as received. All moisture sensitive reactions were performed under
a static nitrogen or argon atmosphere in oven-fried or flame-dried
glassware.
tert-Butyl-(1-methoxymethoxy-3-methylnona-1,2-dienyl)dime-
thylsilane (8a)
To a solution of methoxymethyl ether 6a (2.5 g, 8.4 mmol) in THF
(3 mL) was added s-BuLi (8.4 mL; 10.9 mmol; 1.3 M solution in
hexane) at –78 °C. After stirring for 15 min, MeI (0.78 mL, 12.6
mmol) was added. The mixture was allowed to stir for an additional
15 min before dilution with aq NaHCO3 and Et2O. The aq phase was
extracted with Et2O, the combined organic extracts were dried
(MgSO4), and the solvent was removed in vacuo. Column chroma-
tography (silica gel; 0.625% EtOAc–hexane) gave 8a.
Yield: 2.5 g (8.0 mmol; 96%); pale yellow oil.
IR (film): 2980, 1960, 1465 cm–1.
1H NMR (300 MHz, CDCl3): d = 4.77 (s, 2 H, OCH2O), 3.37 (s, 3
H, OCH3), 2.01–1.95 (m, 2 H, CH2), 1.74 (s 3 H, CH3), 1.48–1.18
(m, 8 H, CH2), 0.94 (s, 9 H, CH3), 0.91–0.85 (m, 3 H, CH3), 0.04 (s,
3 H, CH3), 0.03 (s, 3 H, CH3).
1-(tert-Butyldimethylsilanyl)non-2-yn-1-ol (5a)
To a solution of alkynol 4a (6.0 g, 42.8 mmol) in THF (30 mL) at
–78 °C was added BuLi (17.3 mL; 47.1 mmol; 2.7 M solution in
hexane). The reaction mixture was warmed to 0 °C and allowed to
stir for 30 min. After cooling to –78 °C, TBSCl (7.1 g, 68.5 mmol)
in THF (3 mL) was added via cannula. After stirring for 2 h at r.t.,
the reaction mixture was cooled to –78 °C and BuLi (25.3 mL; 2.7
M solution in hexane) was added. The mixture was stirred for 40
min at –20 °C, and the reaction mixture was subsequently diluted
with aq NaHCO3 and Et2O. The aq phase was extracted with Et2O,
the combined organic extracts dried (MgSO4), and the solvent was
removed in vacuo. Column chromatography (silica gel; 5% EtOAc–
hexane) gave 5a.
13C NMR (75 MHz, CDCl3): d = 193.8, 126.8, 110.9, 94.7, 56.1,
35.0, 32.0, 27.9, 27.1 (3 C), 26.8, 22.8, 21.2, 17.1, 14.3, –6.1, –6.4.
MS (EI): m/z (%) = 218 (46), 230 (53), 243 (23), 268 (12), 312 (1).
HRMS: m/z calcd for C18H36O2Si [M+]: 312.2485; found: 312.2477.
1-Methoxymethoxy-3-methylnona-1,2-diene (16a)
To a solution of allene ether 8a (2.1 g, 6.7 mmol) in THF (10 mL)
was added TBAF (2.1 g, 8.1 mmol) and LiOH (0.16 g, 6.7 mmol).
After stirring at r.t. for 2 h, the reaction mixture was diluted with aq
NaHCO3 and Et2O. The aq phase was extracted with Et2O, the com-
bined organic extracts were dried (MgSO4), and the solvent was re-
moved in vacuo. Column chromatography (silica gel; 0.625%
EtOAc–hexane) gave 16a.
Yield: 10.7 g (41.9 mmol, 98%); yellow oil.
IR (film): 3420, 2940, 1690, 1460, 1250 cm–1.
1H NMR (300 MHz, CDCl3): d = 4.20 (t, 1 H, J = 2.4 Hz, CH), 2.33
(td, 2 H, J = 6.9, 2.4 Hz, CH2), 1.51–1.26 (m, 8 H, CH2), 0.97 (s, 9
Yield: 1.1 g (5.7 mmol; 82%); colorless oil.
IR (film): 2940, 1920, 1470, 1390 cm–1.
Synthesis 2004, No. 5, 786–790 © Thieme Stuttgart · New York

SPECIAL TOPIC
Tetrasubstituted Allene Ethers; Synthesis and Use in Nazarov Reactions
789
1H NMR (300 MHz, CDCl3): d = 6.45 (m, 1 H, HC=C=C), 4.77 (s,
2 H, OCH2O), 3.41 (s, 3 H, OCH3), 2.02 (m, 2 H, CH2), 1.79 (d, 3
H, J = 2.1 Hz, CH3), 1.46–1.23 (m, 8 H, CH2), 0.90–0.85 (m, 3 H,
CH3).
with aq NaHCO3 and Et2O. The aq phase was extracted with Et2O,
the combined organic extracts were dried (MgSO4), and the solvent
was removed in vacuo. Column chromatography (silica gel; 5%
EtOAc–hexane) gave 23a as a ca. 1:1 mixture of E and Z isomers.
13C NMR (75 MHz, CDCl3): d = 189.0, 116.7, 116.0, 94.9, 56.1,
35.9, 32.0, 29.2, 27.6, 22.8, 21.6, 14.3.
Yield: 118 mg (0.35 mmol; 69%); yellow oil.
E + Z-23a
MS (EI): m/z (%) = 68 (16), 81 (14), 128 (100), 142 (12), 198 (1).
HRMS: m/z calcd for C12H22O2 [M+]: 198.1620; found: 198.1615.
IR (film): 2990, 1695, 1630 cm–1.
1H NMR (300 MHz, CDCl3): d = 6.99 (d, 4 H, J = 8.7 Hz, ArH),
6.81 (d, 4 H, J = 8.7 Hz, ArH), 4.10 (s, 1 H, CH), 4.06 (s, 1 H, CH),
3.78 (s, 3 H, OCH3), 3.77 (s, 3 H, OCH), 2.90 (m, 2 H, CH2), 2.68
(m, 2 H, CH2), 2.29 (m, 2 H, CH2), 2.28 (s, 3 H, CH3), 2.27 (s, 3 H,
CH3), 1.93 (m, 2 H, CH2), 1.74 (s, 3 H, CH3), 1.58 (s, 3 H, CH3),
1.28–1.06 (m, 16 H, CH2), 1.05 (m, 3 H, CH3), 1.03 (m, 3 H, CH3),
0.84 (m, 3 H, CH3), 0.82 (m, 3 H, CH3).
2-Hydroxy-3-methyl-5-(1-methylheptylidene)-4-phenylcyclo-
pent-2-enone (18a)
To a solution of allene 16a (200 mg, 1.01 mmol) in THF (5 mL) was
added BuLi (0.45 mL; 1.21 mmol; 2.7 M solution in hexane) at
–78 °C. After stirring for 1 h, morpholino enamide 17 (280 mg, 1.21
mmol) in THF (3 mL) was added via cannula. After stirring for 2 h,
the reaction was transferred by cannula in to a solution of FeCl3
(204 mg, (2.00 mmol) in Et2O (10 mL). The reaction mixture was
diluted with aq NaHCO3 and Et2O. The aq phase was extracted with
Et2O, the combined organic extracts were dried (MgSO4), and the
solvent was removed in vacuo. Column chromatography (silica gel;
5% EtOAc–hexane) gave 18a as a ca. 1:2 mixture of E and Z iso-
mers.
MS (EI): m/z (%) = 69 (37), 91 (26), 101 (13), 115 (20), 135 (21),
147 (47), 175 (100), 204 (49), 270 (32), 340 (59).
HRMS: m/z calcd for C23H32O2 [M+]: 340.2402; found: 340.2416.
2-Amino-3-methyl-5-(1-methylheptylidene)-4-phenylcyclo-
pent-2-enone (20a)
To a solution of allene 16a (200 mg, 1.01 mmol) in THF (5 mL) was
added BuLi (0.45 mL; 1.21 mmol; 2.7 M solution in hexane)
–78 °C. After stirring for 1 h, a-methylcinnamonitrile (19) (144 mg,
0.14 mmol) was added via cannula. The reaction mixture was
warmed to –40 °C and stirred for 1 h. The mixture was then trans-
ferred by cannula into a solution of FeCl3 (204 mg, 2.00 mmol) in
Et2O (10 mL). The reaction mixture was diluted with aq NaHCO3
and Et2O. The aq phase was extracted with Et2O, the combined or-
ganic extracts dried (MgSO4), and the solvent was removed in vac-
uo. Column chromatography (silica gel; 5% EtOAc–hexane) gave
E-20a and Z-20a (ca. 1:2).
Yield: 216 mg (0.73 mmol; 72%); yellow oil.
Compound Z-18a
IR (film): 3250, 1690, 1640, 1400 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.31–7.06 (m, 5 H, ArH), 5.79 (s,
1 H, OH), 4.09 (s, 1 H, CH), 2.95–2.70 (m, 2 H, CH2), 1.71 (d, 3 H,
J = 1.2 Hz, CH3), 1.58 (s, 3 H, CH3), 1.43–1.25 (m, 8 H, CH2), 0.91–
0.85 (m, 3 H, CH3).
13C NMR (75 MHz, CDCl3): d = 190.2, 163.3, 152.9, 150.5, 139.8,
138.4, 131.7, 128.2 (2 C), 127.1 (2 C), 50.2, 37.3, 31.8, 29.5, 26.8,
22.7, 18.5, 14.3, 11.6.
Yield: 195 mg (0.65 mmol; 68% combined yield); orange oils.
MS (EI): m/z (%) = 67 (15), 77 (15), 185 (45), 214 (6), 228 (19), 242
(37), 298 (72).
HRMS: m/z [M+] calcd for C20H26O2: 298.1933; found: 298.1952.
Compound E-20a
IR (film): 3490, 3380, 1650, 1560 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.42–7.06 (m, 5 H, ArH), 4.11 (s,
1 H, CH), 2.28 (s, 3 H, CH3), 1.94–1.89 (m, 2 H, CH2), 1.63 (s, 3 H,
CH3), 1.28–0.87 (m, 8 H, CH2), 0.82 (m, 3 H, CH3).
13C NMR (75 MHz, CDCl3): d = 191.0, 151.2, 142.2, 142.1, 134.6,
133.0, 128.5, 127.9 (2 C), 126.4 (2 C), 51.5, 33.3, 31.8, 29.3, 28.4,
22.6, 21.6, 14.1, 12.3.
Compound E-18a
IR (film): 3300, 1680, 1400 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.29–7.08 (m, 5 H, ArH), 5.74 (s,
1 H, OH), 4.19 (s, 1 H, CH), 2.29 (s, 3 H, CH3), 1.98–1.86 (m, 2 H,
CH2), 1.70 (d, 3 H, J = 0.9 Hz, CH3), 1.28–0.93 (m, 8 H, CH2), 0.84
(t, 3 H, J = 3.3 Hz, CH3).
13C NMR (75 MHz, CDCl3): d = 190.3, 168.2, 150.4, 141.2, 136.6,
131.9, 128.5, 128.0 (2 C), 126.8 (2 C), 50.4, 33.8, 31.9, 29.4, 28.6,
22.8, 21.7, 14.3, 11.7.
MS: m/z (%) = 185 (42), 241 (18), 255 (16), 297 (89).
HRMS: m/z calcd for C20H27NO [M+]: 297.2093; found: 297.2079.
Compound Z-20a
IR (film): 3490, 3380, 1650, 1560 cm–1.
MS (EI): m/z (%) = 105 (65), 115 (29), 129 (26), 149 (21), 167 (13),
185 (54), 209 (14), 228 (100), 241 (28), 298 (69).
HRMS: m/z calcd for C20H26O2 [M+]: 298.1933; found: 298.1948.
1H NMR (300 MHz, CDCl3): d = 7.28–7.01 (m, 5 H, ArH), 4.07 (s,
1 H, CH), 2.95–2.70 (m, 2 H, CH2), 1.63 (d, 3 H, J = 1.2 Hz, CH3),
1.56 (s, 3 H, CH3), 1.50–1.27 (m, 8 H, CH2), 0.87 (m, 3 H, CH3).
13C NMR (75 MHz, CDCl3): d = 191.9, 150.3, 142.4, 142.3, 134.6,
132.8, 129.7, 128.4 (2 C), 126.5 (2 C), 51.2, 37.3, 31.6, 29.3, 26.6,
22.4, 14.7, 14.1, 12.3.
2-Ethyl-4-(4-methoxyphenyl)-3-methyl-5-(1-methylheptyl-
idene)cyclopent-2-enone (23a)
To a solution of allene 16a (200 mg; 1.01 mmol) in THF (5 mL) was
added BuLi (0.45 mL; 1.21 mmol; 2.7 M solution in hexane) at
–78 °C. After stirring for 1 h, enone 21 (0.103 g, 0.50 mmol) in THF
(3 mL) was added via cannula. After stirring for 2 h, the reaction
was diluted with aq NaHCO3 and Et2O. The aq phase was extracted
with Et2O, the combined organic extracts dried (MgSO4), and the
solvent was removed in vacuo. To a solution of crude tertiary alco-
hol 22a in CH2Cl2 (10 mL) was added FeCl3 (82 mg, 0.50 mmol) at
r.t. After stirring at r.t. for 20 min, the reaction mixture was diluted
MS (EI): m/z (%) = 185 (67), 241 (34), 255 (8), 297 (92).
HRMS: m/z calcd for C20H27NO [M+]: 297.2093; found: 297.2083.
Acknowledgment
Acknowledgement is made to the National Institutes of Health
(GM57873) for generous support.
Synthesis 2004, No. 5, 786–790 © Thieme Stuttgart · New York

790
B. K. Tokeshi, M. A. Tius
SPECIAL TOPIC
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Synthesis 2004, No. 5, 786–790 © Thieme Stuttgart · New York