Novel rearrangements of 4-silyl-3-buten-2-ones

Article abstract of DOI:10.1021/jo0109467

Two-4-silyl-3-buten-2-ones, 2a, and 2c, underwent an interesting rearrangement involving migration of the allyl or phenyl group on the silicon atom to the adjacent enone carbon when treated with various bases.

Full text of DOI:10.1021/jo0109467

J . Org. Chem. 2002, 67, 3911-3914
3911
The synthesis of 4-[dimethyl(phenyl)silyl]but-3-en-2-
one (2a ) was accomplished in three steps starting from
commercially available dimethyl(phenyl)silylacetylene
(Scheme 1). Two-carbon homologation of the acetylide
Novel Rea r r a n gem en ts of
4-Silyl-3-bu ten -2-on es
Michael E. J ung* and Grazia Piizzi
Department of Chemistry and Biochemistry,
University of California, Los Angeles, 405 Hilgard Avenue,
Los Angeles, California 90095-1569
Sch em e 1
jung@chem.ucla.edu
Received September 24, 2001
Abstr a ct: Two 4-silyl-3-buten-2-ones, 2a and 2c, under-
went an interesting rearrangement involving migration of
the allyl or phenyl group on the silicon atom to the adjacent
enone carbon when treated with various bases.
anion with acetaldehyde followed by hydride reduction
afforded the desired allylic alcohol 4 in high yield, as a
9:1 E:Z ratio. Subsequent Swern oxidation using trifluo-
roacetic anhydride afforded the desired 4-silylenone 2a
in 51% yield and the unexpected 1,4-adduct 5a in 16%
yield. The latter is formed by the 1,4-addition of dimethyl
sulfide, the byproduct of the Swern oxidation, to the
desired enone followed by base-promoted S-demethyla-
tion.
Alternatively, the silyl propargyl ether 6 could be
prepared from 3-butyn-2-ol according to the procedure
described by Woerpel et al.6 Hydrolysis and stereoselec-
tive reduction using Redal7 afforded exclusively the (E)-
allylic alcohol 4 (Scheme 2). Finally, to avoid the forma-
The increasing use of organosilicon compounds for the
synthesis of complex organic molecules has shed new
light on the chemistry of this group IV element. By means
of the “temporary silicon connection”, Stork et al. achieved
highly regioselective formation of carbon-carbon bonds
via radical, ionic, and cycloadditive processes.1 Moreover,
excellent levels of stereoselectivity have been achieved
in the condensation of chiral silyl reagents with a variety
of electrophiles.2 The success of some of these strategies
arises from the possibility of converting the silicon group
to a hydroxy group. The oxidation of the C-Si bond3 can
be easily carried out using the procedures introduced by
Tamao4 and Fleming,5 which display remarkable compat-
ibility with various organic functionalities. This widely
used methodology has revealed the silicon group to be a
powerful tool for organic synthesis, allowing transforma-
tions that would not otherwise be possible.
Sch em e 2
tion of undesired 1,4-adducts such as 5a , the oxidation
was carried out using PCC to furnish the desired enone
2a in high isolated yield.
Since the 4-silylenone 2a should be suitable for 1,4-
addition by a variety of nucleophiles and its silyl group
should be easily converted into a hydroxyl group by using
the above-mentioned Tamao or Fleming conditions, this
compound should be a useful building block for the
synthesis of our target molecule via a Robinson annula-
tion approach. While investigating the ability of â-silyl
enone 2a to undergo Michael additions in the presence
of alkoxides, we found that along with the products of
presumed polymerization, an unexpected compound, the
well-known 4-phenyl-2-butanone (7), was also formed
(Table 1). Moreover, when fluoride, a well-known silico-
philic anion, was used as the nucleophile, 7 was isolated
in quantitative yield.
The unexpected formation of 7 can be explained by
evoking an initial attack of the nucleophile on the silicon
atom of the silyl enone 2a to give the pentacovalent
silicon anion I, which undergoes a 1,2-migration of the
phenyl group from silicon to the adjacent electrophilic
carbon atom to generate the enolate II as shown in
Scheme 3. After protonation of the enolate, a second
As part of our program directed toward the synthesis
of the AB rings of the naturally occurring cardenolide
ouabain (1a ) and its aglycone ouabagenin (1b), we
decided to investigate the synthesis and the potential
reactivity of several 4-silyl-3-buten-2-ones, 2a -c, in the
hope that we might be able to use them as Michael
acceptors in the Robinson annulation process as sur-
rogates for 4-alkoxyenones to ultimately produce 5-alkoxy-
cyclohex-2-enones. We report here some interesting
rearrangements of these silyl enones.
(1) Stork, G.; Chan, T. Y.; Breault, G. A. J . Am. Chem. Soc. 1992,
114, 7578.
(2) (a) Huang, H.; Panek, J . S. J . Am. Chem. Soc. 2000, 122, 9836.
(b) Zhu, B.; Panek, J . S. Eur. J . Org. Chem. 2001, 1701.
(3) For a review, see: J ones, G.; Landais, Y. Tetrahedron 1996, 52,
7599.
(4) Tamao, K.; Ishida, N.; Kumada, M. J . Org. Chem. 1983, 48, 2120.
(5) Fleming, I.; Henning, R.; Plaut, H. J . Chem. Soc., Chem.
Commun. 1984, 29.
(6) Smitrovich, J . H.; Woerpel, K. A. J . Org. Chem. 2000, 65, 1601.
(7) Hwu, J . R.; Furth, P. S. J . Am. Chem. Soc. 1989, 111, 8834.
10.1021/jo0109467 CCC: $22.00 © 2002 American Chemical Society
Published on Web 05/09/2002

3912 J . Org. Chem., Vol. 67, No. 11, 2002
Notes
Ta ble 1. Rea r r a n gem en t of Silyl En on e 2a to Give
4-P h en ylbu ta n -2-on e 7
Sch em e 5
entry
nucleophile
conditions
yield
1
2
3
4
5
NaOMe (0.4 equiv)
NaOMe (1 equiv)
KOtBu (0.7 equiv)
NaH (1 equiv)
MeOH, reflux, 48 h
MeOH, reflux, 12 h
tBuOH, reflux, 72 h
THF, reflux, 48 h
43%
25%
28%
0%
and subsequent oxidation of the resulting allylic alcohol
afforded the desired â-silyl enone 2c in good isolated
yields.
KF (3 equiv)
wet DMSO, 25 °C, 18 h
100%
nucleophilic attack on the silicon atom generates the
anion III, which then eliminates the neutral silicon
species to afford the benzylic anion IV, which upon
protonation gives the observed product 7.
The two 4-silylbutenones 2b and 2c allowed us to test
two possibilities, namely, (1) would the methyl and allyl
groups on the silicon atom of 2b and 2c, respectively,
migrate to the adjacent electrophilic carbon, and (2)
would the rearrangement continue further with the
desilylation as for the dimethyl(phenyl)silylbutenone 2a .
When the allyl(dimethyl)silyl enone 2c was treated under
the usual basic nucleophilic conditions, the starting
material was converted into the rearranged silanol 12
in quantitative yields (Scheme 6). However, purification
Sch em e 3
Sch em e 6
To our knowledge, the only account of such a phenyl
migration, in the presence of TBAF as a fluoride source,
was reported by Fleming et al.8 Interestingly, at higher
temperatures, even less efficient nucleophiles such as
methoxide (Table 1, entries 1 and 2) and t-butoxide (entry
3) are able to promote this rearrangement. Intrigued by
the unusual reactivity of silyl enone 2a and hoping to
avoid the intramolecular quenching of this class of useful
Michael acceptors, we prepared two other 4-silylbuten-
ones, 2b and 2c. (E)-4-(Trimethylsilyl)-3-buten-2-one 2b
was prepared via the same three-step sequence initially
used for the synthesis of the phenyl analogue 2a (Scheme
4). Trapping of the anion of the silyl acetylene and
by column chromatography on silica gel afforded only the
corresponding disiloxane 13. The C-Si bond was then
oxidatively cleaved using Tamao conditions9 to yield the
homoallylic alcohol 14 in 48% isolated yield. Conversely,
but not surprisingly, no methyl migration was observed
for the trimethylsilyl enone 2b. This clearly suggests that
for migration to occur, the migrating group must be able
to stabilize a negative charge (e.g., phenyl, allyl), and
thus methyl does not migrate. Furthermore, in the case
of the allyl(dimethyl)silyl enone 2c, the desilylation step
observed for 2a does not occur because this would require
an unstabilized homoallylic anion intermediate.10 Fol-
lowing the initial nucleophilic attack to generate the
pentacovalent silicon anion V, a 1,2-migration of the allyl
group to the enone would give the enolate VI and, after
protonation, the observed product 12 (Scheme 7).
Sch em e 4
hydride reduction of the resulting alcohol 8 gave the
allylic alcohol 9 as a 6:1 E:Z ratio. As before, the Swern
oxidation of the allylic alcohol 9 yielded a 5:2 mixture of
the desired enone 2b and the product of 1,4-addition of
dimethyl sulfide (5b). Interestingly, keeping the temper-
ature at -78 °C throughout the oxidation gave the enone
as the only product in 75% yield. 4-Allyl(dimethyl)silyl-
3-buten-2 one (2c) was prepared by bis-silylation of
3-butyn-2-ol with 1 equiv of allyl(dimethyl)silyl chloride
to give a mixture of the desired monosilylated compound
10 (49%) and the bis-silylated product 11 (19%) (Scheme
5). The bis-silylated product 11 was then hydrolyzed to
the propargyl alcohol 10 in quantitative yield. Reduction
Sch em e 7
Finally, we were interested in testing several protode-
silylation conditions with the â-silyl enones 2a and 2c
(8) Fleming, I.; Newton, T. W.; Sabin, V.; Zammattio, F. Tetrahedron
1992, 48, 7793.
(9) Tamao, K.; Ishida, N.; Tanaka, T.; Kumada, M. Organometallics
1983, 2, 1694.

Notes
J . Org. Chem., Vol. 67, No. 11, 2002 3913
only the most significant absorption bands are reported in cm-1
(Scheme 8). Denmark et al.11 showed that the Si-Ar bond
of â-silyl acrylates could be cleaved with dry HCl at 80
.
Thin-layer chromatography (TLC) was carried out by the use of
silica gel 60 F254 0.2 mm alumina-backed plates. Visual
detection was performed with ultraviolet light or using phos-
phomolybdic acid or permanganate stain. Flash column chro-
matography was performed using silica gel 60 (230-400 mesh)
using compressed air. All solvents/reagents were purified using
literature procedures. All reactions were performed under an
atmosphere of argon unless otherwise noted.
Sch em e 8
4-P h en ylb u t a n -2-on e (7). The starting enone 2a (16 mg,
0.078 mmol) was dissolved in dimethylformamide (DMF, 5 mL)
and treated with water (5 drops) and potassium fluoride (13 mg,
0.235 mmol). The resulting mixture was stirred for 18 h at 20
°C. Then, the solvent was removed under vacuum and the
residue dissolved in dichloromethane (10 mL) and washed with
water (2 mL). The aqueous layer was extracted with dichlo-
romethane (2 × 20 mL), and the combined organic phases were
dried over MgSO4. The solvent was removed under vacuum to
afford the phenyl ketone 7 (11 mg, quantitative) as a colorless
oil that did not require further purification. The spectroscopic
properties of this compound were consistent with those reported
in the Aldrich catalog. The same compound was also obtained
using sodium methoxide or potassium t-butoxide with the
appropriate solvent under reflux, as shown in Table 1.
°C in high yield. Sieburth et al.12 accomplished the same
goal using triflic acid. Unfortunately, the â-silyl enones
2a and 2c proved to be unstable to strongly acidic
electrophilic conditions. Attempted bromodesilylation of
2c with Br2 at -78 °C proved to be unsuccessful, giving
only decomposition of the starting enone. Moreover,
treatment of the enone 2a with dry HCl, BBr3/AcOH,
HBF4-Et2O, or triflic acid, also resulted in decomposi-
tion. Ultimately, the protodesilylation of the allylsilane
2c was achieved using an excess of boron trifluoride-
acetic acid complex to give the desired fluorosilane 16
with still some of the hydrolysis product 17 (here 1:1)
(Scheme 8).13 The phenylsilane was converted into the
fluorosilane 16 in quantitative yield by this process.
Interestingly, under these protic, mildly nucleophilic
conditions, no allyl or phenyl migration was observed.
Presumably, even if the initial protonation of the carbonyl
group can promote the intramolecular shift, the forma-
tion of the pentacovalent silicon anionic intermediate
(such as I or V), which is needed to trigger the rear-
rangement, does not occur under these conditions.
In summary, we have shown that 4-silylbutenones
bearing a phenyl (2a ) or allyl group (2c) on the silicon
atom undergo an intramolecular Michael addition under
mildly nucleophilic conditions. The process can stop at
the corresponding â-silyl ketone or continue further
depending upon the extent of stabilization of the anion
intermediate. Enones such as 2a and 2b can be useful
Michael acceptors for organic synthesis. However, our
results showed that their use may be limited to soft,
nonsilicophilic anions or to acidic conditions.
(()-4-(Tr im eth ylsilyl)-bu t-3-yn -2-ol (8). Trimethylsilylacet-
ylene (2.0 mL, 14.15 mmol) was dissolved in THF (20 mL) at
-78 °C and treated with n-butyllithium (6.8 mL, 16.98 mmol)
over 4 min. After the reaction was stirred for 15 min, acetalde-
hyde (1.6 mL, 28.3 mmol) was added and the yellow solution
turned colorless immediately. After the mixture was stirred for
2 h at -78 °C, the reaction was quenched with aqueous
saturated NH4Cl (10 mL) and extracted with ethyl acetate (4 ×
50 mL). The organic layers were dried over MgSO4, and the
solvent was removed under vacuum to afford a pale yellow oil.
Flash column chromatography (4:1 hexanes/ethyl acetate) af-
forded the desired compound 8 (1.6 g, 80%). The 1H NMR
spectrum of 8 was consistent with the that reported in the
literature.17 13C NMR (CDCl3, 400 MHz) δ: 107.6, 88.4, 58.8,
24.2, -0.14. IR (neat): 3331, 2175, 1371, 1251, 1118, 1047, 839
cm-1
.
(()(E) a n d (Z)-4-(Tr im et h ylsilyl)-b u t -3-en -2-ol (9). The
alkyne 8 (830 mg, 5.84 mmol) was dissolved in THF (5 mL) and
added to a solution of lithium aluminum hydride (2.9 mL, 2.92
mmol) in the same solvent (10 mL) at 0 °C. After the mixture
was stirred for 2 h, the cooling bath was removed and the
mixture stirred at 20 °C for 18 h. The reaction was then
quenched by addition of water (1 mL) at 0 °C and the mixture
extracted with ethyl acetate (3 × 30 mL). The combined organic
layers were washed with brine and dried over MgSO4. The
solvent was removed under vacuum to yield the allylic alcohol
9 as a 6:1 inseparable mixture of E:Z isomers that did not need
further purification. The spectroscopic properties of 9 were
consistent with those reported in the literature.18
(E)-4-(Tr im et h ylsilyl)-b u t -3-en -2-on e (2b ) a n d 4-(Tr i-
m eth ylsilyl)-4-(m eth ylth io)-bu ta n -2-on e (5b). A solution of
dimethyl sulfoxide (0.35 mL, 4.5 mmol) in dichloromethane (30
mL) was treated with trifluoroacetic anhydride (0.48 mL, 3.37
mmol) dropwise at -78 °C. After the mixture was stirred for 10
min, a solution of the allylic alcohol 9 (162 mg, 1.16 mmol) in
dichloromethane (5 mL) was added via syringe. The resulting
mixture was stirred at -78 °C for 50 min, and then triethy-
lamine (1.4 mL, 10.12 mmol) was added dropwise. After the
mixture was stirred for 5 min, the cooling bath was removed
and the mixture allowed to warm to 20 °C over 45 min. The
clear solution was treated with water (10 mL) and extracted with
Exp er im en ta l Section
Gen er a l. 1H NMR spectra were obtained at 200.132, 400.132,
or 500.132 MHz as indicated. 13C NMR spectra were recorded
at 100.625 or 125.773 MHz as indicated. 1H NMR and 13C NMR
data are reported in parts per million (δ) downfield from
tetramethylsilane. Resonance patterns are reported with the
following notations: br (broad), s (singlet), d (doublet), t (triplet),
q (quartet), and m (multiplet). Second-order spectra in which
coupling cannot be obtained by inspection are reported as
multiplets, with the center of the signal indicated by the δ value
given. Infrared spectra were recorded as neat liquid films, and
(13) Fleming, I.; Henning, R.; Parker, D. C.; Plaut, H. E.; Sanderson,
P. E. J . J . Chem. Soc., Perkin Trans. 1 1995, 317.
(14) Fleming, I.; Takaki, K.; Thomas, A. P. J . Chem. Soc., Perkin
Trans. 1 1987, 2269.
(15) Panek, J . S.; Yang, M.; Solomon, J . S. J . Org. Chem. 1993, 58,
1003.
(16) Gibson, S. E.; Tustin, G. J . J . Chem. Soc., Perkin Trans. 1 1995,
2427.
(17) Burgess, K.; J ennings, L. D. J . Am. Chem. Soc. 1991, 113, 6129.
(18) (a) J enkins, P. R.; Gut, R.; Wetter, H.; Eschenmoser, A. Helv.
Chim. Acta 1979, 62, 1922. (b) Carter, M. J .; Fleming, I.; Percival, A.
J . Chem. Soc., Perkin Trans. 1 1981, 2415.
(10) One may also consider these rearrangements to be fundamen-
tally cationic in nature or at least similar to cationic rearrangements
in which the pentacovalent silicon atom provides a nucleophilic “push”
for migration to a somewhat cationic center, an unusual sort of push-
pull effect. Thus, phenyl and allyl are good migrating groups because
they can bond easily to an adjacent partially cationic center. We thank
Professor Ian Fleming for his input on the mechanism of this
rearrangement.
(11) Denmark, S. E.; Hurd, A. R.; Sacha, H. J . J . Org. Chem. 1997,
62, 1668.
(12) Sieburth, S. McN.; Lang, J . J . Org. Chem. 1999, 64, 1780.

3914 J . Org. Chem., Vol. 67, No. 11, 2002
Notes
1
dichloromethane (3 × 80 mL). The combined organic layers were
dried over MgSO4 and the solvent removed under vacuum to
yield a 5:2 mixture of 2b and 5b. Purification by flash column
chromatography (5:1 hexanes/ethyl acetate, 1% triethylamine)
afforded the pure enone 2b (86 mg, 54%) and 5b (34 mg, 17%).
The spectroscopic properties of 2b were consistent with those
(Z)-Isom er . H NMR (CDCl3, 500 MHz) δ: 6.92 (d, J ) 13.9
Hz, 1H), 6.36 (d, J ) 13.9 Hz, 1H), 5.76 (m, 1H), 4.82 (m, 2H),
2.24 (s, 3H), 1.66 (d, J ) 8.1 Hz, 2H), 0.14 (s, 6H).
4-(Hyd r oxyd im eth ylsilyl)-6-h ep ten -2-on e (12) a n d 1,1′-
Bis(2-oxo-6-h epten -4-yl)tetr am eth yldisiloxan e (13): Meth od
A. Sodium metal (4 mg, 0.16 mmol) was dissolved in methanol
(2 mL) followed by the addition of a solution of the enone 2c (34
mg, 0.20 mmol) in the same solvent (1 mL). The resulting
solution was refluxed for 20 h. After the mixture was cooled to
20 °C, the reaction was quenched by the addition of saturated
NH4Cl (2 mL) and extracted with dichloromethane (3 × 30 mL).
The combined organic layers were dried over MgSO4 followed
by solvent removal under vacuum to afford the silanol 12 (23
mg, 62%).20 1H NMR (CDCl3, 500 MHz) δ: 5.75 (m, 1H), 5.05
(m, 2H), 2.74 (bs, 1H), 2.68 (dd, J ) 18.4, 6.95 Hz, 1H), 2.61
(dd, J ) 18.4, 5.3 Hz, 1H), 2.31 (m, 1H), 2.20 (s, 3H), 1.99 (btd,
J ) 14.2, 8.9 Hz, 1H), 1.20 (m, 1H), 0.17 (s, 3H), 0.15 (s, 3H).
1
reported in the literature.18b,19 Compound 5b. H NMR (CDCl3,
500 MHz) δ: 2.76 (bd, J ) 6.6 Hz, 2H), 2.34 (dt, J ) 6.6, 1.0 Hz,
1H), 2.25 (s, 3H), 2.14 (s, 3H), 0.12 (s, 9H). 13C NMR (CDCl3,
500 MHz) δ: 207.9, 45.8, 30.5, 27.3, 17.2, -2.8.20 When the
reaction was carried out keeping the temperature at -78 °C
throughout, only the desired enone 2b was isolated in 75% yield.
(()-4-(2-P r op en yld im et h ylsilyl)-b u t -3-yn -2-ol (10). 3-
Butyn-2-ol (0.3 mL, 3.8 mmol) was dissolved in THF (10 mL) at
-78 °C and then treated with n-butyllithium (3.3 mL, 8.36
mmol) dropwise. The resulting cloudy mixture was stirred for 5
min and then warmed to 20 °C for 1.5 h. The clear solution was
then cooled back to -78 °C and treated with allyldimethylsilyl
chloride (0.6 mL, 3.8 mmol) dropwise. After stirring for 30 min,
the mixture was warmed to 20 °C and stirred for 18 h. Then,
the reaction was quenched by the addition of water (20 mL) at
0 °C and extracted with dichloromethane (3 × 100 mL). The
combined organic layers were washed with brine and dried over
MgSO4. After solvent removal under vacuum, the resulting crude
oil was purified by flash column chromatography (3:1 hexanes/
ethyl acetate) to afford the desired monosilylated compound 10
(314 mg, 49%) and the bis-silyl compound 11 (191 mg, 19%).
Treatment of the bis-silylated compound 11 with 8 drops of
concentrated HCl in a 1:1 mixture of THF and dioxane at 20 °C
for 2 h afforded the desired compound 10 in quantitative yield.20
1H NMR (CDCl3, 400 MHz) δ: 5.80 (m, 1H), 4.90 (m, 2H), 4.53
(m, 1H), 1.80 (d, J ) 5.3 Hz, 1H), 1.62 (d, J ) 7.0 Hz, 2H), 1.44
(d, J ) 6.6 Hz, 3H), 0.15 (s, 6H). 13C NMR (CDCl3, 500 MHz)
δ: 133.7, 125.3, 113.8, 108.5, 86.6, 58.5, 24.1, 23.6, -2.4. IR
Meth od B. The starting enone 2c (10 mg, 0.059 mmol) was
dissolved in DMF (2 mL) and treated with water (5 drops) and
potassium fluoride (3 mg, 0.059 mmol). The resulting mixture
was stirred for 12 h at 20 °C. Then, the solvent was removed
under vacuum and the residue dissolved in dichloromethane (10
mL) and washed with water (2 mL). The aqueous layer was
extracted with dichloromethane (2 × 20 mL), and the combined
organic phases were dried over MgSO4. The solvent was removed
under vacuum to afford the silanol 12 (8 mg, 74%). Purification
by flash column chromatography (4:1 hexanes/ethyl acetate)
afforded exclusively the dimer 13 (7 mg, 64%).20 1H NMR (CDCl3,
500 MHz) δ: 5.68 (m, 2H), 4.94 (m, 4H), 2.38 (m, 4H), 2.24 (m,
2H), 2.11 (s, 6H), 1.91 (m, 2H), 1.33 (m, 2H), 0.05 (s, 12H). 13C
NMR (CDCl3, 500 MHz) δ: 208.7, 138.2, 115.5, 42.5, 33.9, 30.1,
21.8, 21.7, -0.5, -0.7. IR (neat): 3074, 2957, 1716, 1637, 1255,
1051, 835, 781 cm-1
.
(neat): 3343, 3078, 2963, 2175, 1630, 1251, 1045, 808 cm-1
.
4-Hyd r oxy-6-h ep ten -2-on e (14). The dimer 13 (18 mg, 0.051
mmol) was dissolved in a 1:1 mixture of methanol and THF (6
mL) and treated with potassium fluoride (23 mg, 0.406 mmol),
sodium bicarbonate (42 mg, 0.508 mmol), and 30% H2O2 (0.2
mL, 1.01 mmol). The resulting mixture was stirred at 20 °C for
6 h and then refluxed for 2 h. The cloudy mixture was allowed
to cool to 20 °C and the reaction quenched by the addition of
saturated Na2S2O3 (5 mL). After stirring for 30 min, the mixture
was poured into a separatory funnel and extracted with ethyl
acetate (4 × 30 mL). The combined organic layers were dried
under MgSO4, and solvent removal under vacuum yielded a
crude oil. Purification by flash column chromatography (2:1
hexanes/ethyl acetate) afforded the alcohol 14 (6 mg, 48%) as a
colorless oil. 1H NMR (CDCl3, 500 MHz) δ: 5.80 (m, 1H), 5.12
(m, 2H), 4.11 (m, 1H), 2.93 (bs, 1H), 2.63 (dd, J ) 17.6, 3.0 Hz,
1H), 2.55 (dd, J ) 17.6, 8.9 Hz, 1H), 2.24 (m, 2H), 2.21 (s, 3H).
13C NMR (CDCl3, 500 MHz) δ: 209.4, 134.0, 117.9, 66.7, 49.0,
(E)-4-(2-P r op en yld im eth ylsilyl)-bu t-3-en -2-on e (2c). The
alkyne 10 (300 mg, 1.78 mmol) was dissolved in THF (5 mL)
and added to a suspension of lithium aluminum hydride (68 mg,
1.78 mmol) in the same solvent (10 mL) at 0 °C. After the
reaction was stirred for 1.5 h, the cooling bath was removed and
the mixture stirred at 20 °C for 45 min. The reaction was then
quenched by addition of saturated NH4Cl (1 mL) at 0 °C and
extracted with ethyl acetate (3 × 20 mL). The combined organic
layers were washed with brine and dried over MgSO4. The
solvent was removed under vacuum to yield a 9:1 mixture of
the (E)- and (Z)-allylic alcohols. The crude material was used in
the following step with further purification.
A solution of dimethyl sulfoxide (0.19 mL, 2.4 mmol) in
dichloromethane (15 mL) was treated with trifluoroacetic an-
hydride (0.26 mL, 1.84 mmol) dropwise at -78 °C. After the
reaction was stirred for 10 min, a solution of the crude allylic
alcohol (174 mg, 1.02 mmol) in dichloromethane (3 mL) was
added via syringe. The resulting mixture was stirred at -78 °C
for 50 min, and then triethylamine (0.68 mL, 4.9 mmol) was
added dropwise. After the reaction was stirred for 1.5 h at -78
°C, the cooling bath was removed and the mixture allowed to
warm for 5 min. Then, the clear solution was poured into a
separatory funnel containing a solution of 2 M HCl (8 mL) and
extracted with dichloromethane (3 × 50 mL). The combined
organic layers were dried over MgSO4, and the solvent was
removed under vacuum to yield a 10:1 mixture of the (E)-enone
2c and its (Z)-isomer. Purification by flash column chromatog-
raphy (4:1 hexanes/ethyl acetate) afforded the pure (E)-enone
2c (122 mg, 61%) and the pure (Z)-isomer (10 mg, 5%).20
40.72, 30.65. IR (neat): 3404, 2922, 1716 cm-1
.
(E)-4-(Flu or odim eth ylsilyl)-bu t-3-en -2-on e (16). The enone
2a (37 mg, 0.184 mmol) was dissolved in dichloromethane (2
mL) and treated with boron trifluoride-acetic acid complex (0.1
mL, 0.725 mmol), and the resulting deep-yellow solution was
stirred for 20 h at 20 °C. Then, the dark-red mixture was poured
into a separatory funnel containing saturated NaHCO3 (5 mL)
and extracted with dichloromethane (3 × 20 mL). The combined
(bright-green) organic layers were dried over MgSO4, and solvent
removal yielded 16 (23 mg, quantitative) as a brown-green oil.
Attempted purification by flash column chromatography afforded
the correspondent silanol 17 exclusively.20 1H NMR (CDCl3, 500
MHz) δ: 6.88 (dd, J ) 19.5, 3.8 Hz, 1H), 6.58 (d, J ) 19.3 Hz,
1H), 2.30 (s, 3H), 0.37 (d, J ) 0.37, 6H). 13C NMR (CDCl3, 500
MHz) δ: 198.1, 144.4 (d, J ) 12.5 Hz), 140.7 (d, J ) 67.5 Hz),
26.5, -1.48 (d, J ) 60 Hz). 19F NMR (CDCl3, 500 MHz) δ: -163.
1
(E)-Isom er (2c). H NMR (CDCl3, 500 MHz) δ: 6.94 (d, J )
19.3 Hz, 1H), 6.40 (d, J ) 19.3 Hz, 1H), 5.68 (m, 1H), 4.82 (m,
2H), 2.22 (s, 3H), 1.58 (d, J ) 8.0 Hz, 2H), 0.09 (s, 6H). 13C NMR
(CDCl3, 500 MHz) δ: 198.2, 145.5, 143.6, 133.4, 113.8, 26.1, 22.5,
-4.1. IR (neat): 2959, 1678, 1630, 1251, 995, 844 cm-1
.
Su p p or tin g In for m a tion Ava ila ble: Spectra for com-
pounds mentioned and text providing experimental procedures
for compounds 3, 4, and 5a . This material is available free of
charge via the Internet at http://pubs.acs.org.
(19) Otera, J .; Manda, T.; Shiba, M.; Saito, T.; Shimohata, K.;
Takamori, K.; Kawasaki, Y. Organometallics 1983, 2, 332.
(20) The structure was assigned by high-field proton and carbon
NMR. We did not obtain HRMS data due to the instability of this
material.
J O0109467