Polycyclic Aromatic Compounds via Radical Cyclizations of Benzannulated Enyne-Allenes Derived from Ireland-Claisen Rearrangement

Article abstract of DOI:10.1021/jo035036z

A new synthetic sequence involving the use of Ireland-Claisen rearrangement of propargylic acetates to form the corresponding benzannulated enyne-allenes followed by Schmittel cyclization to generate benzofulvene biradicals for radical cyclizations leadin

Full text of DOI:10.1021/jo035036z

P olycyclic Ar om a tic Com p ou n d s via Ra d ica l Cycliza tion s of
Ben za n n u la ted En yn e-Allen es Der ived fr om Ir ela n d -Cla isen
Rea r r a n gem en t
Yonghong Yang, J effrey L. Petersen,† and Kung K. Wang*
Department of Chemistry, West Virginia University, Morgantown, West Virginia 26506-6045
kung.wang@mail.wvu.edu
Received J uly 17, 2003
A new synthetic sequence involving the use of Ireland-Claisen rearrangement of propargylic
acetates to form the corresponding benzannulated enyne-allenes followed by Schmittel cyclization
to generate benzofulvene biradicals for radical cyclizations leading to polycyclic aromatic compounds
was established. Treatment of 9-fluorenone (8) with the lithium acetylide 9 followed by acetic
anhydride produced the propargylic acetate 10. A sequence of reactions occurred after 10 was
converted to the corresponding silyl ketene acetal 11. An initial Ireland-Claisen rearrangement
produced the benzannulated enyne-allene 12, which then underwent a Schmittel cyclization reaction
to generate the benzofulvene biradical 13. A subsequent intramolecular radical-radical coupling
then produced the formal Diels-Alder adduct 14, which in turn underwent a prototropic
rearrangement to give the silyl ester 15 and, after hydrolysis, the carboxylic acid 16 in 57% overall
yield from 10 in a single operation. An intramolecular acylation reaction of 16 produced the ketone
17. The carboxylic acids 24-26 were likewise prepared from the diaryl ketones 18-20, respectively.
However, the intramolecular [2 + 2] cycloaddition reaction of the benzannulated enyne-allene 33
having a tert-butyl group at the allenic terminus occurred preferentially, producing the 1H-cyclobut-
[a]indenyl acetic acid 35 as the predominant product.
SCHEME 1
In tr od u ction
Biradicals generated from cyclization of (Z)-1,2,4-
heptatrien-6-ynes (enyne-allenes) and the benzannulated
analogues under mild thermal conditions provide many
opportunities for subsequent synthetic applications.1
Cyclization of the enyne-allene 1 could proceed either via
the C2-C7 pathway (Myers-Saito cyclization) to form the
R,3-didehydrotoluene/naphthalene biradical 22 or via the
C2-C6 pathway (Schmittel cyclization) to produce the
fulvene/benzofulvene biradical 3 (Scheme 1).3 The enyne-
allenes bearing an aryl substituent or a sterically de-
manding group, such as the tert-butyl group or the
trimethylsilyl group, at the alkynyl terminus favor the
Schmittel cyclization pathway.
subsequent Myers-Saito cyclization reaction involves
producing the allenic moiety via thermolysis of propargyl
vinyl ethers to promote the [3,3] sigmatropic Claisen
rearrangement at 150 °C.4 The corresponding Lewis acid
catalyzed [3,3] sigmatropic Claisen rearrangement pro-
moted by AgBF4 was also successfully adopted for the
preparation of the benzannulated enyne-allenes at 25 °C.4
The silyl ketene acetals of propargylic acetates have
also been reported to undergo facile Ireland-Claisen
rearrangement to produce, after hydrolysis, the corre-
sponding allenyl acetic acids.5 Specifically, the propar-
gylic acetate 4 was treated with lithium diisopropylamide
One of the synthetic methods that has been used to
prepare in situ the benzannulated enyne-allenes for the
* To whom correspondence should be addressed. Phone: (304) 293-
3068, ext 6441. Fax: (304) 293-4904.
† To whom correspondence concerning the X-ray structures should
be addressed. Phone: (304) 293-3435, ext 6423. Fax: (304) 293-4904.
E-mail: jeffrey.petersen@mail.wvu.edu.
(1) For reviews, see: (a) Nicolaou, K. C.; Dai, W.-H. Angew. Chem.,
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10.1021/jo035036z CCC: $25.00 © 2003 American Chemical Society
Published on Web 10/04/2003
J . Org. Chem. 2003, 68, 8545-8549
8545

Yang et al.
SCHEME 2
SCHEME 3
(LDA) followed by trapping the resulting enolate with
trimethylsilyl chloride to form the silyl ketene acetal 5
at -78 °C (Scheme 2). When the reaction mixture
warmed to 40 °C, the Ireland-Claisen rearrangement
occurred to produce the silyl ester 6, which after hydroly-
sis furnished the allenyl acetic acid 7 in 50% overall yield.
However, this reaction sequence did not appear to have
been adopted for the synthesis of enyne-allenes. The
mildness of the reaction conditions and the ready avail-
ability of a variety of silyl ketene acetals make the
transformation well suited for the preparation of ther-
mally labile enyne-allenes and the benzannulated ana-
logues. We now report our findings in using this synthetic
strategy to produce in situ the benzannulated enyne-
allenes for radical cyclizations leading to polycyclic
aromatic compounds.
Resu lts a n d Discu ssion
Condensation between 9-fluorenone (8) and the lithium
acetylide 96 as reported previously furnished the corre-
sponding alkoxide,7 which was captured by acetic anhy-
dride to afford the propargylic acetate 10 (Scheme 3).
Treatment of 10 with LDA at -78 °C followed by trapping
the resulting enolate with tert-butyldimethylsilyl chloride
(TBDMSCl) then gave the silyl ketene acetal 11.8 A series
of reactions then occurred upon warming the reaction
mixture to 45 °C, including an Ireland-Claisen rear-
rangement to form the benzannulated enyne-allene 12
followed by a Schmittel cyclization to generate the
benzofulvene biradical 13. An intramolecular radical-
radical coupling then produced the formal Diels-Alder
adduct 14, which in turn underwent a prototropic rear-
rangement to give the silyl ester 15 and, after hydrolysis,
the carboxylic acid 16 in 57% overall yield from 10 in a
single operation. The cascade transformation from 12 to
15 is reminiscent of what was observed previously in a
chlorinated enyne-allene system derived from condensa-
tion between 8 and 9 to form the corresponding propar-
gylic alcohol followed by treatment of the propargylic
alcohol with thionyl chloride.7
moted intramolecular acylation reaction then produced
the polycyclic aromatic ketone 17 in 88% yield. The
structure of 17 was established by X-ray structure
analysis (see Supporting Information).
The diaryl ketone 18,9 readily obtained by oxidation
of the corresponding hydrocarbon, 4H-cyclopenta[def]-
phenanthrene,10 was also selected for condensation with
9 leading to the propargylic acetate 21 in 81% yield
(Table 1). The acetate 21 was converted to the carboxylic
acid 2411 via the tandem sequence of Ireland-Claisen
rearrangement and Schmittel cyclization. Similarly, the
use of the diaryl ketone 1912a,b and benzophenone (20)
led to the carboxylic acids 25 and 26, respectively. It is
worth noting that the structures of 24 and 25 contain a
benzo[ghi]fluoranthene unit and a dihydrobenzo[ghi]-
fluoranthene unit, respectively. Several synthetic meth-
ods for benzo[ghi]fluoranthene and related derivatives
The pendent carboxylic acid group in 16 also provided
the opportunity for an intramolecular acylation reaction.
Conversion of 16 to the corresponding acid chloride with
thionyl chloride followed by an aluminum chloride pro-
(9) (a) Harvey, R. G.; Abu-shqara, E.; Yang, C. J . Org. Chem. 1992,
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Supporting Information).
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Commun. 1973, 3, 67-72.
8546 J . Org. Chem., Vol. 68, No. 22, 2003

Radical Cyclizations of Benzannulated Enyne-Allenes
TABLE 1. Syn th esis of P olycyclic Ar om a tic Ca r boxylic
Acid s fr om Dia r yl Keton es
SCHEME 4
reaction mixture showed only very broad peaks in the
aromatic region, indicating that intermolecular acylation
occurred to give polymerized adducts. It was envisioned
that 28 could serve as a precursor for ring contraction15
to form 29 having an indeno-fused dihydrocorannulene
moiety. The acid chloride of 25 was also used for the
acylation reaction in the hope that the intermolecular
reaction could be avoided. Unfortunately, such an at-
tempt was also unsuccessful. Treatment of 25 with
concentrated sulfuric acid at room temperature for 12 h
resulted in the recovery of unreacted 25. On the other
hand, the aryl ketone 3011 was readily obtained from 26
in 70% yield (eq 1).
a
The crude product was used for the next step without isolation.
b
Overall yield from the diaryl ketone.
have been reported.12b,c,13 One of these derivatives was
used in the first synthesis of the bowl-shaped corannu-
lene.12b,c Development of new synthetic methods for cor-
annulene and related compounds has attracted renewed
interest and considerable attention in recent years.14
The acid 24 was also readily converted to the acid
chloride 27 with thionyl chloride (Scheme 4). However,
attempts to promote the intramolecular acylation reac-
tion of 27 using aluminum chloride as the catalyst to form
28 were unsuccessful. The 1H NMR spectrum of the crude
With the propargylic acetate 32, derived from 2,2-
dimethylpropiophenone (31), the 1H-cyclobut[a]indenyl
acetic acid 35 was obtained as the predominant product
along with ca. 1% of the 11H-benzo[b]fluorenyl acetic acid
36 (Scheme 5). Conceivably, the initially formed benzan-
nulated enyne-allene 33 underwent a [2 + 2] cycloaddi-
tion reaction preferentially, perhaps also via the biradical
34, to produce 35. The low propensity for 34 to undergo
the radical-radical coupling reaction involving a double
bond of the phenyl substituent to produce the formal
Diels-Alder adduct leading to 36 may be attributed to
the emergence of the nonbonded steric interactions
between the silyl ester group and the tert-butyl group
depicted in 34 along the pathway toward 36. Such a
change of the reaction pathway was also observed previ-
ously in the chlorinated enyne-allene system.7
(13) (a) Chang, H.-F.; Cho, B. P. J . Org. Chem. 1999, 64, 9051-
9056. (b) Crombie, D. A.; Shaw, S. J . Chem. Soc. C 1969, 2489-2490.
(c) Dosa, P. I.; Schleifenbaum, A.; Vollhardt, K. P. C. Org. Lett. 2001,
3, 1017-1020. (d) Brooks, M. A.; Scott, L. T. J . Am. Chem. Soc. 1999,
121, 5444-5449. (e) Sarobe, M.; J enneskens, L. W.; Wiersum, U. E.
Tetrahedron Lett. 1997, 38, 4689-4692. (f) Plater, M. J . Tetrahedron
Lett. 1994, 35, 6147-6150. (g) Studt, P.; Win, T. Liebigs Ann. Chem.
1983, 519.
(14) (a) Scott, L. T.; Cheng, P.-C.; Hashemi, M. M.; Bratcher, M. S.;
Meyer, D. T.; Warren, H. B. J . Am. Chem. Soc. 1997, 119, 10963-
10968. (b) Reisch, H. A.; Bratcher, M. S.; Scott, L. T. Org. Lett. 2000,
2, 1427-1430. (c) Ansems, R. B. M.; Scott, L. T. J . Am. Chem. Soc.
2000, 122, 2719-2724. (d) Bronstein, H. E.; Choi, N.; Scott, L. T. J .
Am. Chem. Soc. 2002, 124, 8870-8875. (e) Sygula, A.; Rabideau, P.
W. J . Am. Chem. Soc. 1998, 120, 12666-12667. (f) Sygula, A.;
Rabideau, P. W. J . Am. Chem. Soc. 1999, 121, 7800-7803. (g) Sygula,
A.; Rabideau, P. W. J . Am. Chem. Soc. 2000, 122, 6323-6324. (h)
Sygula, A.; Xu, G.; Marcinow, Z.; Rabideau, P. W. Tetrahedron 2001,
57, 3637-3644. (i) Marcinow, Z.; Grove, D. I.; Rabideau, P. W. J . Org.
Chem. 2002, 67, 3537-3539. (j) Sygula, A.; Karlen, S. D.; Sygula, R.;
Rabideau, P. W. Org. Lett. 2002, 4, 3135-3137. (k) Seiders, T. J .;
Baldridge, K. K.; Siegel, J . S. J . Am. Chem. Soc. 1996, 118, 2754-
2755. (l) Mehta, G.; Sarma, P. V. V. S. Chem. Commun. 2000, 19-20.
For reviews, see: (m) Scott, L. T.; Bronstein, H. E.; Preda, D. V.;
Ansems, R. B. M.; Bratcher, M. S.; Hagen, S. Pure Appl. Chem. 1999,
71, 209-219. (n) Mehta, G.; Rao, H. S. P. Tetrahedron 1998, 54, 13325-
13370. (o) Rabideau, P. W.; Sygula, A. Acc. Chem. Res. 1996, 29, 235-
242. (p) Scott, L. T. Pure Appl. Chem. 1996, 68, 291-300.
As in the case of the chlorinated enyne-allene system,
the use of the ketone 3716 having the keto group incor-
(15) (a) Nongrum, F. M.; Myrboh, B. Synthesis 1987, 845-846. (b)
Taylor, E. C.; Chiang, C.-S.; McKillop, A.; White, J . F. J . Am. Chem.
Soc. 1976, 98, 6750-6752. (c) Wiberg, K. B.; Furtek, B. L.; Olli, L. K.
J . Am. Chem. Soc. 1979, 101, 7675-7679.
(16) (a) Klemm, L. H.; Shabtai, J .; Taylor, D. R. J . Org. Chem. 1968,
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Soc. 1980, 102, 3538-3548.
J . Org. Chem, Vol. 68, No. 22, 2003 8547

Yang et al.
SCHEME 5
aromatic derivatives of benzo[ghi]fluoranthene and 11H-
benzo[b]fluorene were thus produced. In several cases,
the [2 + 2] cycloaddition reaction of the benzannulated
enyne-allenes also occurred, leading to the corresponding
1H-cyclobut[a]indenyl acetic acids.
Exp er im en ta l Section
P r op a r gylic Aceta te 10. The following procedure is rep-
resentative for the preparation of the propargylic acetates. To
a solution of 1.63 g (8.07 mmol) of 1-(2-ethynylphenyl)-2-
phenylethyne in 50 mL of diethyl ether under a nitrogen
atmosphere at 0 °C was added 3.00 mL of a 2.5 M solution of
n-butyllithium (7.50 mmol) in hexanes. The reaction mixture
was then allowed to warm to room temperature. After 30 min
at room temperature, a solution of 1.13 g (6.27 mmol) of
9-fluorenone (8) in 50 mL of diethyl ether was introduced
dropwise via cannula. After an additional 2 h at room tem-
perature, a solution of 0.78 g (7.64 mmol) of acetic anhydride
in 50 mL of diethyl ether was introduced, and the reaction
mixture was stirred for 4 h before 20 mL of water was added.
The organic layer was separated, and the aqueous layer was
back-extracted with diethyl ether. The combined organic
extracts were washed with brine and water, dried over
magnesium sulfate, and concentrated. A mixture of hexanes
and diethyl ether (3:1, 10 mL) was added to the residue, and
the solution was cooled to 0 °C. A solid precipitate appeared
after ca. 15 min. The solid precipitate was collected by
filtration and then washed with hexanes to furnish 2.20 g of
10 (5.19 mmol, 83%) as a light brown solid: mp 120-122 °C;
SCHEME 6
1
IR 2219, 1749, 1229, 757 cm-1; H NMR δ 7.91 (2 H, d, J )
7.7 Hz), 7.65 (2 H, d, J ) 7.7 Hz), 7.50 (2 H, tm, J ) 7.4, 2
Hz), 7.40 (2 H, td, J ) 7.4, 0.7 Hz), 7.35-7.20 (9 H, m), 2.02
(3 H, s); 13C NMR δ 169.1, 144.1, 139.9, 132.5, 131.75, 131.70,
129.8, 128.41, 128.35, 128.25, 128.18, 127.8, 126.1, 126.0,
124.7, 123.1, 120.0, 93.2, 89.7, 87.8, 84.1, 79.6, 21.8; MS m/z
424 (M+), 380, 366. HRMS: calcd for C31H20O2, 424.1463;
found, 424.1466.
Ca r boxylic Acid 16. The following procedure is represen-
tative for the preparation of the carboxylic acids. To a flask
containing 1.60 mL of a 2.5 M solution of n-butyllithium (4.00
mmol) in hexanes under a nitrogen atmosphere at 0 °C were
added 0.56 mL (4.00 mmol) of diisopropylamine and then 5
mL of THF. After 30 min at 0 °C, the reaction mixture was
cooled to -78 °C. A solution of 0.85 g (2.00 mmol) of 10 in 15
mL of THF was introduced dropwise via cannula. After 30 min
at -78 °C, 1 mL of HMPA and 4 mL of a 1.0 M solution of
TBDMSCl (4.00 mmol) in THF were introduced. The reaction
mixture was allowed to warm to room temperature slowly and
then heated to 45 °C. After an additional 12 h at 45 °C, the
reaction mixture was allowed to cool to room temperature and
a mixture of 10 mL of acetic acid and 3.3 mL of water was
introduced. After 12 h, 20 mL of diethyl ether was added and
the organic layer was separated. The aqueous layer was back-
extracted with diethyl ether. The combined organic layers were
washed with water (5 × 30 mL), dried over magnesium sulfate,
and concentrated. Flash column chromatography (silica gel/
25% acetone in hexanes) provided 0.487 g of 16 (1.15 mmol,
57%) as a yellow solid: mp 258-260 °C; IR 3500-2600 (br),
porated in the six-membered ring to prepare the prop-
argylic acetate 39 for the cascade transformation appears
to reduce the nonbonded steric interactions along the
pathway leading to the Diels-Alder adduct (Scheme 6).
As a result, the [2 + 2] cycloaddition adduct 41 and the
Diels-Alder adduct 42 were produced in essentially
equal amounts. In the case of 40, prepared from 3817
having a five-membered ring, the effect was particularly
dramatic and resulted in the formation of the Diels-
Alder adduct 44 predominantly.
1
1708, 756 cm-1; H NMR δ 8.05 (1 H, d, J ) 7.7 Hz), 8.02 (1
H, d, J ) 7.7 Hz), 7.97 (1 H, d, J ) 6.2 Hz), 7.68 (1 H, d, J )
7.7 Hz), 7.64-7.44 (9 H, m), 7.29 (1 H, t, J ) 6.9 Hz), 7.10 (1
H, t, J ) 7.4 Hz), 6.67 (1 H, d, J ) 7.7 Hz), 5.18 (1 H, dd, J )
10.5, 1.4 Hz), 3.76 (1 H, dd, J ) 16.6, 2.2 Hz), 2.55 (1 H, dd, J
) 16.6, 10.9 Hz); 13C NMR δ 177.5, 147.3, 141.6, 140.3, 140.2,
138.6, 137.83, 137.80, 136.4, 134.2, 131.8, 130.8, 130.2, 128.83,
128.75, 128.0, 127.80, 127.77, 127.58, 127.51, 125.9, 124.6,
123.9, 123.7, 121.8, 119.8, 41.9, 38.5; MS m/z 424 (M+), 378,
365. HRMS: calcd for C31H20O2, 424.1463; found, 424.1466.
Keton e 17. The following procedure is representative for
the intramolecular acylation reaction. To a flask containing
0.25 g (0.59 mmol) of 16 under a nitrogen atmosphere was
Con clu sion s
The Ireland-Claisen rearrangement of the propargylic
acetates was successfully adopted for the synthesis of the
benzannulated enyne-allenes in situ for the subsequent
Schmittel cyclization to generate benzofulvene biradicals
for a cascade sequence of reactions. Several polycyclic
(17) Lemmen, P.; Lenoir, D. Chem. Ber. 1984, 117, 2300-2313.
8548 J . Org. Chem., Vol. 68, No. 22, 2003

Radical Cyclizations of Benzannulated Enyne-Allenes
added 5.0 mL (68.5 mmol) of thionyl chloride. After 3 h at room
temperature, the excess thionyl chloride was removed in vacuo
to yield the crude acid chloride (IR 1794 cm-1) as a brown-
yellow oil. To the solution of the crude acid chloride in 130
mL of methylene chloride at 0 °C was added 0.21 g (1.57 mmol)
of anhydrous aluminum chloride. The reaction mixture was
allowed to warm to room temperature slowly. After 12 h, 10
mL of a 2 M solution of hydrochloric acid was added and the
organic layer was separated. The aqueous layer was back-
extracted with methylene chloride. The combined organic
layers were washed with saturated aqueous sodium bicarbon-
ate (3 × 50 mL) and water, dried over magnesium sulfate, and
concentrated. Flash column chromatography (silica gel/50%
methylene chloride in hexanes) furnished 0.21 g of 17 (0.52
mmol, 88%) as orange crystals: mp 323-325 °C; IR 1662, 774,
°C, the reaction mixture was cooled to -78 °C. A solution of
the crude propargylic acetate 32 in 15 mL of THF was
introduced slowly via cannula. After 30 min at -78 °C, 1.2
mL of HMPA and 2.0 mL of a 1.0 M solution of TBDMSCl
(2.0 mmol) in THF were introduced. The reaction mixture was
allowed to warm to room temperature slowly and then heated
at 45 °C. After an additional 12 h at 45 °C, the reaction mixture
was allowed to cool to room temperature. A mixture of 7 mL
of acetic acid and 3 mL of water was introduced. After 12 h,
20 mL of diethyl ether was introduced, and the organic layer
was separated. The aqueous layer was back-extracted with
diethyl ether. The combined organic layers were washed with
water (5 × 30 mL), dried over magnesium sulfate, and
concentrated. Flash column chromatography (silica gel/25%
acetone in hexanes) provided 0.142 g of 35 (0.35 mmol, 35%
from 31) as an orange solid: mp 204-206 °C; IR 3500-2600
(br), 1707, 751, 693 cm-1; 1H NMR δ 7.96 (2 H, d, J ) 7.2 Hz),
7.67 (1 H, d, J ) 7.4 Hz), 7.55-7.10 (11 H, m), 3.85 (2 H, s),
1.22 (9 H, s); 13C NMR δ 176.5, 153.7, 151.7, 148.4, 147.5,
142.8, 135.5, 129.3, 129.2, 129.0, 128.9, 128.8, 128.6, 127.6,
126.2, 124.0, 123.6, 120.1, 114.8, 77.2, 36.8, 33.2, 29.0; MS m/z
406 (M+), 360, 349. HRMS: calcd for C29H26O2, 406.1933;
found, 406.1915. The formation of 36 was detected in the crude
reaction products with 1H NMR signals (partial) at δ 8.57 (1
H, d, J ) 8.9 Hz), 6.96 (1 H, t, J ) 6.7 Hz), 6.23 (1 H, d, J )
7.7 Hz), 5.41 (1 H, d, J ) 11 Hz), 3.23 (1 H, d, J ) 16 Hz), 2.30
(1 H, dd, J ) 16, 11 Hz).
1
708 cm-1; H NMR δ 8.08 (1 H, d, J ) 7.4 Hz), 7.97 (1 H, dd,
J ) 7.7, 1.5 Hz), 7.94 (1 H, d, J ) 7.7 Hz), 7.63-7.43 (9 H, m),
7.33 (1 H, t, J ) 7.2 Hz), 7.14 (1 H, t, J ) 7.7 Hz), 6.85 (1 H,
d, J ) 7.7 Hz), 4.51 (1 H, d, J ) 13.6 Hz), 3.64 (1 H, dd, J )
12.9, 2.5 Hz), 3.24 (1 H, dd, J ) 13.6, 12.9 Hz); 13C NMR δ
199.2, 145.9, 144.0, 141.6, 139.9, 137.9, 137.2, 135.9, 134.7,
133.4, 130.7, 130.4, 130.1, 129.9, 128.9, 128.8, 128.7, 128.1,
128.0, 127.8, 127.6, 127.5, 126.9, 126.4, 126.1, 124.4, 123.8,
121.3, 44.4, 41.8; MS m/z 406 (M+), 389, 378. HRMS: calcd
for C31H18O, 406.1358; found, 406.1347. Recrystallization of
17 from CH2Cl2/2-propanol produced a crystal suitable for
X-ray structure analysis (see Supporting Information).
Ca r boxylic Acid s 35 a n d 36. To a solution of 0.227 g (1.12
mmol) of 1-(2-ethynylphenyl)-2-phenylethyne in 20 mL of
diethyl ether under a nitrogen atmosphere at 0 °C was added
0.44 mL of a 2.5 M solution of n-butyllithium (1.10 mmol) in
hexanes. The reaction mixture was then allowed to warm to
room temperature. After 30 min at room temperature, a
solution of 0.162 g (1.00 mmol) of 31 in 20 mL of diethyl ether
was introduced slowly via cannula. After an additional 2 h at
room temperature, a solution of 0.112 g (1.10 mmol) of acetic
anhydride in 10 mL of diethyl ether was introduced. After an
additional 4 h, 20 mL of water was introduced. The organic
layer was separated, and the aqueous layer was back-extracted
with diethyl ether. The combined organic extracts were washed
with brine and water, dried over magnesium sulfate, and
concentrated in vacuo. The crude propargylic acetate 32 was
used for the next step without further purification.
Ack n ow led gm en t. The financial support of the
National Science Foundation (CHE-9618676) and the
Petroleum Research Fund, administered by the Ameri-
can Chemical Society, to K.K.W. is gratefully acknowl-
edged. J .L.P. acknowledges the support (CHE-9120098)
provided by the Chemical Instrumentation Program of
the National Science Foundation for the acquisition of
a Siemens P4 X-ray diffractometer in the Department
of Chemistry at West Virginia University.
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures and spectroscopic data for 21, 22, 24-26, 30, and 41-
44;1H and 13C NMR spectra of compounds 10, 16, 17, 21, 22,
24-26, 30, 35, and 41-44; and ORTEP drawings and tables
of crystallographic data for the X-ray diffraction analysis of
17, 24, and 30 in PDF format. This material is available free
of charge via the Internet at http://pubs.acs.org.
To a flask containing 0.80 mL of a 2.5 M solution of
n-butyllithium (2.00 mmol) in hexanes under a nitrogen
atmosphere at 0 °C were added 0.28 mL (2.00 mmol) of
diisopropylamine and then 2 mL of THF. After 30 min at 0
J O035036Z
J . Org. Chem, Vol. 68, No. 22, 2003 8549