Carboxylate methylenation with a functionalized silylmethyl anion: A two-step synthesis of 2-substituted allylic alcohols from esters

Full text of DOI:10.1021/jo961639h

J . Org. Chem. 1996, 61, 9617-9620
9617
silyl)methyl]magnesium chloride6 or with [(trimethylsi-
lyl)methyl]lithium and CeCl3.2 From esters, however, the
best yields of allylic trimethylsilanes have been obtained
using [(trimethylsilyl)methyl]magnesium chloride in con-
junction with CeCl3.3-5,10 We have found that a reagent
Ca r boxyla te Meth ylen a tion w ith a
F u n ction a lized Silylm eth yl An ion : A
Tw o-Step Syn th esis of 2-Su bstitu ted Allylic
Alcoh ols fr om Ester s
Tammy J . Mickelson,† J ennifer L. Koviach, and
Craig J . Forsyth*
Department of Chemistry, University of Minnesota,
Minneapolis, Minnesota 55455-0431
Received August 23, 1996X
Allylic silanes have proven to be very useful intermedi-
ates in organic synthesis.1 A reliable method for the
synthesis of substituted allylic silanes is the double
addition of silylmethyl nucleophiles to carboxylic acid
derivatives followed by Peterson-type elimination.2-6
Because the carbon-silicon bonds of aryl- and hetero-
atom-substituted7,8 silanes may be cleaved under mild
oxidative conditions to afford the corresponding alcohols,
we envisioned that the synthetic utility of the double
addition-Peterson elimination sequence could be ex-
tended conveniently by the use of appropriately substi-
tuted silylmethyl nucleophiles. The derived aryl- or
heteroatom-substituted allylic silane products should
provide ready access to a variety of additional allylic
functionality via the derived allylic alcohols. In particu-
lar, we have found that the use of a CeCl3-modified,
oxygen-substituted silylmethyl nucleophile does allow for
a direct and general two-step conversion of carboxylic acid
esters into highly functionalized allylic alcohol products
via a Peterson olefination-Tamao oxidation process. The
details of this novel two-step transformation of carboxylic
acid esters into 1,1-disubstituted ethylene products are
reported here.
A key factor for successful conversion of carboxylic acid
derivatives into allylic trimethylsilanes via the double
addition-Peterson elimination sequence is the use of
silylmethyl nucleophiles of low basicity. In 1978 Demuth
showed that monoaddition of [(trimethylsilyl)methyl]-
lithium to simple esters gave R-trimethylsilyl ketones.9
Because the R-trimethylsilyl ketone products undergo
facile enolization in the presence of excess [(trimethyl-
silyl)methyl]lithium, the addition of a second equivalent
of the basic lithium anion does not occur to an appreciable
extent. However, double addition to esters and subse-
quent Peterson-type elimination can be accomplished
using the less basic reagents derived from [(trimethyl-
derived from Tamao’s hydroxymethyl anion equivalent,
[(dimethylisopropoxysilyl)methyl]magnesium chloride
(1),11,12 and CeCl3 provides good yields of the isopropoxy-
substituted allylic silanes. Furthermore, these products
can be converted into the corresponding allylic alcohols
in high yields.
The utility of this two-step ester to allylic alcohol
transformation was examined initially using methyl (S)-
3-(benzyloxy)-2-methylpropionate (2),13 a substrate that
is susceptible to potential base-induced R-epimerization
and â-elimination. Treatment of 2 with the reagent
prepared from 3 equiv each of 1 and carefully prepared
CeCl3 in THF at -65 °C to rt over 4 h, followed by workup
and chromatography, reproducibly gave allylic silane 3
in >80% yield (Table 1). In contrast to the multistep
protocols developed to induce Peterson elimination in
reactions of carboxyl derivatives and (trialkylsilyl)methyl
nucleophiles, double addition as well as elimination
occurred spontaneously under the reaction conditions. A
simple aqueous NH4Cl quench and extractive workup
gave the allylic (dimethylisopropoxy)silane 3 directly. The
observed in situ Peterson-type elimination may be facili-
tated by the cerium salts formed in the reaction mixture.
The success of this process was highly dependent upon
the purity and handling of the reagents and products.
In modifying the recently published procedure for the
preparation of 1,12 we found that the use of magnesium
activated by the method of Baker and co-workers14 gave
consistently good results. Also, proper preparation and
handling of the CeCl3 was critical to the success of this
procedure.2-4 As previously noted,5 partial dehydration
of CeCl3(H2O)7 under somewhat rigorous drying condi-
tions was necessary for the generation of a viable
silylmethyl nucleophile. Although the conditions we used
for CeCl3 dehydration (0.3 Torr and 150 °C for 7 h) have
been shown to give the monohydrate CeCl3‚H2O,15 the
use of 3 equiv each of the CeCl3 prepared this way and
the Grignard reagent gave very reproducible and satis-
factory results. Less vigorous dehydrating conditions or
the use of commercially available “anhydrous” CeCl3
generally resulted in little or no carboxylate addition/
elimination. Prolonged reaction times or exposure of the
* To whom correspondence should be addressed. University of
Minnesota, Department of Chemistry, 207 Pleasant Street S.E.,
Minneapolis, MN 55455. E-mail: forsyth@chemsun.chem.UMN. EDU.
Office: (612) 624-0218. Lab: (612) 626-7978. FAX: (612) 626-7541.
† Present address: Department of Chemistry, University of Roch-
ester, Rochester, NY 14627-0216.
X Abstract published in Advance ACS Abstracts, December 1, 1996.
(1) Fleming, I. In Comprehensive Organic Synthesis; Heathcock, C.
H., Ed.; Pergamon Press: Oxford, 1991; Vol. 2, pp 595-628.
(2) Anderson, M. B.; Fuchs, P. L. Synth. Commun. 1987, 17, 621-
635.
(3) Narayanan, B. A.; Bunnelle, W. H. Tetrahedron Lett. 1987, 28,
6261-6264.
(10) Bunnelle, W. H.; Narayanan, B. A. Org. Synth. 1990, 69, 89-
95.
(4) Lee, T. V.; Porter, J . R.; Roden, F. S. Tetrahedron Lett. 1988,
29, 5009-5012.
(11) Tamao, K.; Ishida, N. Tetrahedron Lett. 1984, 25, 4245-4248.
(12) Tamao, K.; Ishida, N.; Ito, Y.; Kumada, M. Org. Synth. 1990,
69, 96-105.
(5) Lee, T. V.; Channon, J . A.; Cregg, C.; Porter, J . R.; Roden, F. S.;
Yeoh, H. T.-L. Tetrahedron 1989, 45, 5877-5886.
(6) Fleming, I.; Pearce, A. J . Chem. Soc., Perkin Trans. I 1981, 251.
(7) Tamao, K.; Ishida, N.; Tanaka, T.; Kumada, M. Organometallics
1983, 2, 1694-1696.
(8) Tamao, K.; Kakui, T.; Akita, M.; Iwahara, T.; Kanatani, R.
Tetrahedron 1983, 39, 983-990.
(9) Demuth, M. Helv. Chim. Acta 1978, 61, 3136.
(13) Keck, G. E.; Palani, A.; McHardy, S. F. J . Org. Chem. 1994,
59, 3112-3122.
(14) Baker, K. V.; Brown, J . M.; Hughe, N.; Skarnulis, A. J .; Sexton,
A. J . Org. Chem. 1991, 56, 698-703.
(15) Evans, W. J .; Feldman, J . D.; Ziller, J . W. J . Am. Chem. Soc.
1996, 118, 4581-4584.
S0022-3263(96)01639-8 CCC: $12.00 © 1996 American Chemical Society

9618 J . Org. Chem., Vol. 61, No. 26, 1996
Notes
Ta ble 1. Meth yl Ester Meth ylen a tion w ith 1 a n d CeCl3, a n d th e Der ived Alcoh ol Oxid a tion P r od u cts
a
b
Yields are of isolated and chromatographically homogeneous products. Yield for 14 is based on recovered starting material; the
isolated yield is 56%.
crude reaction product to aqueous acidic conditions led
to cleavage of the isopropyl silyl ether of 3. The resultant
silanol condensed readily to afford the corresponding
disiloxane, which proved to be only somewhat less useful
synthetically.16 Chromatographically purified 3 could be
oxidized under Tamao’s conditions12 to give allylic alcohol
4 cleanly and in excellent yield. A convenient alternative,
however, involved oxidative treatment of the crude
product mixture containing allylic silane 3 to give 4 in
similar overall yields from 2. The two-step ester to allylic
alcohol transformation could thus be accomplished re-
producibly in ca. 80% yield.
To determine whether in situ enolization and epimer-
ization of the stereogenic center R to the carboxylic acid
ester occurred, the allylic alcohol products (+)- and (-)-4
derived from each enantiomer of 2 were derivatized and
analyzed as the Mosher esters. Separate treatment of
(+)- and (-)-4 with (S)-R-methoxy-R-(trifluoromethyl)-
phenylacetyl chloride and DMAP in CH2Cl2 gave (R,R)-
and (R,S)-MTPA esters 5. Although these diastereomers
The scope of this carboxylate methylenation procedure
was surveyed with a variety of different methyl esters,
including methyl benzoates (6, 9, and 12), methyl cin-
namate (15), and methyl 2-phenylpropiolate (18, Table
1). Using the same procedures as for the conversion of
2 into 3 and 4, each of these esters was converted
efficiently into the corresponding allylic silanes and
alcohols, respectively. Consistent with previous use of
Ce(III)-modified nucleophiles, only 1,2-addition and no
1,4-addition was observed in the case of the R,â-unsatur-
ated esters 15 and 18. The resultant silylmethyl-
substituted 1,3-diene 16 and the enyne 19 underwent
smooth oxidation to the corresponding allylic alcohols 17
and 20. Although silylmethyl methylenation with 1 and
CeCl3 works well for a number of highly functionalized
esters, nucleophilic addition to methyl 4-nitrobenzoate
resulted in a complex mixture of chromatographically
unstable products. In contrast, methyl 4-fluorobenzoate
(12) underwent satisfactory methylenation, and subse-
quent Tamao oxidation of the resultant silane 13 also
proceeded well. Silylmethyl methylenation of methyl
4-methoxybenzoate (9) with 1 and CeCl3 gave the ex-
pected allylic siloxane 10 in excellent yield. Thus, aryl
esters with either electron-withdrawing or electron-
donating substituents as well as R,â-unsaturated esters
are good substrates for the methylenation-oxidation
sequence.
In summary, the use of Tamao’s hydroxymethyl anion
equivalent 1 with stoichiometric CeCl3 is effective for the
facile conversion of a variety of methyl esters into the
corresponding isopropoxy-substituted allylic silanes with-
out the necessity of inducing a Peterson-type elimination
in a discrete step. The isopropyl silyl ether is stable
under the reaction conditions, yet allows oxidative cleav-
age of the functionalized allylic silanes to give the
corresponding allylic alcohols in high yields.17 The
conditions for each step are both mild and general. If
care is taken to avoid silyl ether cleavage of the allylic
silane intermediates, then both methylenation and oxi-
dation may be accomplished without appreciable side
reactions. Carboxylic acid esters are converted into
substituted allylic alcohols without detectable R-epimer-
ization or â-elimination (2), and neither 1,4-addition (15,
could not be distinguished readily by chromatography,
the allylic methylene proton resonances in their H NMR
displayed unique splitting patterns. No trace of the
1
corresponding epimeric was detected in either (R,R)- or
1
(R,S)-5 by 500 MHz H NMR spectroscopy. Thus, the
integrity of the R-stereogenic center of 2 was largely, if
not entirely, retained in the conversion to 4.
(16) The resultant disiloxanes could be oxidized to the corresponding
allylic alcohols under the same conditions as used for 3, but lower yields
of allylic alcohol products were obtained.

Notes
J . Org. Chem., Vol. 61, No. 26, 1996 9619
3200-3550, 2866, 1649, 1453 cm-1; 1H NMR (200 MHz) δ 7.2-
7.35 (m, 5H), 4.68 (s, 2H), 4.51 (s, 2H), 4.00 (m, 1H), 3.53 (dd, J
) 5.2, 9.1 Hz, 1H), 3.27 (dd, J ) 7.9, 9.1 Hz, 1 H), 2.36 (m, 1H),
1.64 (s, 2H), 1.14 (d, J ) 6.4 Hz, 6 H), 1.11 (d, J ) 6.9 Hz, 3H),
0.13 (s, 6H); 13C NMR (75 MHz) δ 148.81, 138.84, 128.30 (2C),
127.52 (2C), 127.41, 107.58, 74.90, 72.94, 65.01, 41.03, 26.54,
25.78, 17.13, -1.31 (2C); MS 307.2 (M + H)+; HRMS calcd for
18) nor overoxidation occurs under these conditions.
Because of the ease of execution, mild reaction conditions,
and overall efficiency, this sequence should prove to be
generally useful for the conversion of carboxylic acid
esters into highly functionalized derivatives of the com-
mon 1,1-disubstituted ethylene moiety.
C
18H31O2Si [M + H]+ 307.2093, found 307.2081, calcd for C18H34
-
NO2Si (M + NH4)+ 324.2359, found 324.2350.
(S)-3 [[R]23D +49° (c 0.12, CHCl3)] was similarly prepared from
(S)-2.
Exp er im en ta l Section
Gen er a l Meth od s. Unless otherwise noted, all reactions
were carried out under an argon or nitrogen atmosphere in oven-
dried glassware using standard syringe, cannula, and septa
techniques. Diethyl ether and tetrahydrofuran were distilled
from Na/benzophenone ketyl under N2. Dichloromethane, 2-pro-
panol, and triethylamine were distilled from CaH2 under N2.
All other solvents were used as received. (Chloromethyl)-
dimethylsilyl chloride and CeCl3‚7H2O (99%) were purchased
from Aldrich Chemical Co., Milwaukee, WI. (Chloromethyl)-
dimethylisopropoxysilane (21) was prepared from (chlorometh-
yl)dimethylsilyl chloride as previously described12 and was
distilled immediately prior to use. Flash chromatography was
performed using Baker flash silica gel 60 (40 µm) and the solvent
systems indicated. Analytical and preparative TLC was per-
formed with 0.25 and 0.50 mm EM silica gel 60 F254 plates,
respectively. NMR spectra are referenced to residual CHCl3 at
7.25 (1H) and 77.0 ppm (13C). HRMS data were obtained by CI
using a Finnigan MAT 95 spectrometer and isobutane or NH3.
Combustion analyses were performed by M-H-W Laboratories
(Phoenix, AZ).
(R )-4-(Be n zyloxy)-2-(h yd r oxym e t h yl)-3-m e t h yl-1-b u -
ten e (4). Oxidative cleavage of the isopropoxysilane to the
allylic alcohol was accomplished by slight modification of the
literature procedure.12 To a stirred solution of (R)-3 (182 mg,
596 µmol) in THF and methanol (2.5 mL each) at rt were added
KHCO3 (237 mg, 2.37 mmol) and KF‚2H2O (446 mg, 4.74 mmol).
After the mixture was stirred for 5 min, an aqueous solution of
30% H2O2 (400 µL, 2.85 mmol) was added, forming a milky
suspension. The reaction mixture was allowed to stir at rt for
22 h, at which point TLC showed no remaining 3. An aqueous
50% solution of Na2S2O3 (5 mL) was added over 30 min to the
reaction mixture, the resulting mixture was filtered through a
fritted glass funnel under vacuum, and the organic solvents were
removed by rotary evaporation. The residual aqueous suspen-
sion was extracted with diethyl ether (4 × 10 mL), and the
combined ether extracts were washed with brine. The organic
phase was dried over anhyd MgSO4, filtered, and concentrated.
Silica gel chromatography (hexanes-ethyl acetate, 4:1) gave
(R)-4 (120 mg, 582 mmol, 98%) as a clear, volatile oil: [R]23
D
-278° (c 0.134, CHCl3); IR (neat) 2971, 2927, 2871, 1632 cm-1
;
(R)-4-(Ben zyloxy)-3-m eth yl-2-(isop r op oxyd im eth ylsilyl)-
1-bu ten e ((R)-3). CeCl3‚7H2O (3.00 g, 8.05 mmol) was stirred
in a 100 mL round bottom flask at 0.3 Torr and 150 °C for 7 h.
The CeCl3 was then cooled to 0 °C and stirred while THF (15
mL) was slowly added. The resulting suspension was allowed
to warm to rt and stir for ca. 12 h. The homogeneous white
suspension was then cooled to -78 °C prior to addition of the
Grignard reagent, which was prepared from 21 as follows.
Mg turnings were placed in a 50 mL round bottom flask and
stirred with a 1.6 × 3.0 cm Teflon-coated magnetic stir bar under
argon for 3 d, at which time the Mg was pulverized to a black
powder. A portion (783 mg, 32.21 mmol) was removed and
placed in a 50 mL two-necked round bottom flask fitted with a
reflux condenser. The whole apparatus was heated with a heat
gun while under vacuum (0.3 Torr). After the apparatus was
cooled to rt under argon, 2 mL of a solution of 21 (1.33 g, 8.05
mmol) in THF (10 mL) followed by 1,2-dibromoethane (100 µL)
was added to the charcoal-colored Mg powder. The remaining
THF solution of 21 was added over 30 min, allowing the black
Mg suspension to reflux vigorously without external heating.
After complete addition, the suspension was externally heated
and maintained at reflux for 30 min. After the suspension was
cooled to rt, the black supernatant was transferred via syringe
over 10 min to the previously prepared, -78 °C, stirred THF
suspension of CeCl3. The resulting dark gray mixture was
stirred at -78 °C for an additional 15 min before neat 213 (558
mg, 2.68 mmol) was added dropwise over 3 min. The resulting
mixture was allowed to warm slowly to rt and stir for 4 h. TLC
indicated complete disappearance of 2. The reaction mixture
was cooled to 0 °C and diluted with diethyl ether (35 mL) before
a 0 °C saturated aqueous solution of NH4Cl (5 mL) was added.
The organic layer was separated and washed with water (20 mL)
and brine (20 mL). The combined aqueous phases were ex-
tracted with diethyl ether (2 × 50 mL). The combined organic
extracts were dried over anhyd MgSO4, filtered, and concen-
trated to an oil by rotary evaporation. Silica gel chromatography
(hexanes-ethyl acetate, 20:1) gave (R)-3 (732 mg, 2.39 mmol,
1H NMR (200 MHz) δ 7.2-7.39 (m, 5H), 5.10 (d, J ) 1.2 Hz,
1H), 4.95 (s, 1H), 4.52 (s, 2H), 4.09 (br s, 2H), 3.44 (m, 2H), 2.57
(m, 1 H), 2.50 (br s, 1H), 1.10 (d, J ) 7.0 Hz, 3H); 13C NMR (75
MHz) δ 151.71, 137.97, 128.45 (2C), 127.70 (2C), 110.99, 75.39,
73.23, 65.68, 37.40, 16.85; HRMS calcd for C13H19O2 (M + H)+
207.1386, found 207.1375. Anal. Calcd for C13H18O: C, 75.685;
H, 8.8128; O, 15.562. Found: C, 75.90; H, 8.55; O, 15.73.
(S)-4 was similarly prepared from (S)-3: [R]23D +273° (c 0.107,
CHCl3); HRMS calcd for C13H19O2 (M + H)+ 207.1386, found
207.1388.
[(R)-4-(Ben zyloxy)-2-(h yd r oxym eth yl)-3-m eth yl-1-bu ten -
2-yl]m eth yl (R)-(+)-r-m eth oxy-r-(tr iflu or om eth yl)p h en yl-
a ceta te [(R,R)-5]. To a stirred rt solution of (R)-4 (49.0 mg,
238 µmol) in CH2Cl2 (2 mL) were sequentially added 4-(N,N-
dimethylamino)pyridine (34.8 mg, 285 µmol) and (S)-R-methoxy-
R-(trifluoromethyl)phenylacetyl chloride (72.0 mg, 285 µmol).
After 10 min, TLC showed no remaining 4. The reaction mixture
was diluted with CH2Cl2 (2 mL) and sequentially washed with
saturated aqueous NaHCO3, H2O, and saturated aqueous NaCl
(2 mL each). The organic phase was dried (anhyd MgSO4),
filtered, and concentrated. Purification by silica gel column
chromatography (hexanes-ethyl acetate, 8:1) gave (R,R)-5 (94.5
mg, 224 µmol, 94%) as a colorless oil: 1H NMR (300 MHz) δ
7.20-7.55 (m, 10H), 5.12 (s, 1H), 5.03 (s, 1H), 4.84, (d, J ) 13.1
Hz, 1H), 4.78, (d, J ) 13.1 Hz, 1H), 4.47 (s, 2H), 3.54 (s, 3H),
3.27-3.43 (m, 2H), 2.49 (m, 1H), 1.08 (d, J ) 7.0 Hz, 3H); 13C
NMR (75 MHz) δ 145.2, 138.4, 129.6, 128.8, 128.41, 128.37,
127.5, 127.4, 113.9, 74.4, 73.0, 68.2, 55.5, 37.2, 16.6; HRMS calcd
for C23H29F3NO4 (M + NH4)+ 440.2050, found 440.2065.
(S,R)-5 was similarly prepared from (S)-4:
1H NMR (300
MHz) δ 7.25-7.51 (m, 10H), 5.12 (s, 1H), 5.03 (s, 1H), 4.86 (d, J
) 13.0 Hz, 1H), 4.73 (d, J ) 13.0 Hz, 1H), 4.45 (s, 2H), 3.53 (s,
3H), 3.37 (m, 2H), 2.48 (m, 1H), 1.06 (d, J ) 7.0 Hz, 3H); 13C
NMR (75 MHz) δ 166.6, 145.2, 138.2, 129.6, 128.42, 128.38,
127.6, 127.3, 113.9, 74.4, 73.0, 68.2, 55.8, 37.2, 16.6; HRMS calcd
for C23H29F3NO4 (M + NH4)+ 440.2050, found 440.2040.
Allylic Sila n es 7, 10, 13, 16, a n d 19. Treatment of methyl
benzoate (6), methyl 4-methoxybenzoate (9), methyl 4-fluoroben-
zoate (12), methyl cinnamate (15), and methyl 2-phenylpropi-
olate (18) with the reagent derived from 21 (3.0 equiv), Mg (12
equiv), and CeCl3 (3.0 equiv) under the conditions described for
the preparation of 3 gave, after workup and chromatography,
the corresponding allylic silanes 7, 10, 13, 16, and 19, respec-
tively, as colorless oils.
89%) as a colorless oil: [R]23 -46° (c 0.12, CHCl3); IR (neat)
D
(17) The stability of the isopropyl silyl ether proved useful for
demonstrating the utility of this methodology; however, the scope of
this chemistry may be expanded by the use of functionalized alkyl
groups in place of the isopropyl group of 1. For example, methyl
carboxylate methylenation using the reagent derived from (chloro-
methyl)dimethyl(allyloxy)silane also gave the corresponding allylic
silane (data not shown). Such alternatively functionalized silylmethyl
anions may lead to allylic silanes suitable for a variety of subsequent
intramolecular transformations via this new type of temporary silicon
connection.
3-(Isop r op oxyd im eth ylsilyl)-2-p h en ylp r op en e (7). Ester
6 (654 mg, 4.80 mmol) gave 7 (981 mg, 4.19 mmol, 87% yield):
IR (neat) 3083, 2970, 1617, 1028 cm-1 1H NMR (300 MHz) δ
;

9620 J . Org. Chem., Vol. 61, No. 26, 1996
Notes
7.41 (m, 2H), 7.29 (m, 3H), 5.20 (s, 1H), 4.98 (s, 1H), 3.95 (m,
1H), 2.14 (s, 2H), 1.09 (d, J ) 6.1 Hz, 6H), -0.01 (s, 6H); 13C
NMR (75 MHz) δ 145.5, 142.6, 128.1, 127.3, 126.4, 111.0, 65.1,
26.4, 25.8, -1.4; HRMS calcd for C14H22OSi (M + H)+ 235.1520,
found 235.1524.
2-(4-Meth oxyp h en yl)-2-p r op en -1-ol (11). Silane 10 (50
mg, 0.19 mmol) gave 11 as a white solid (22 mg, 0.13 mmol,
71% yield): IR (thin film) 3236, 1624, 1609, 1028 cm-1; 1H NMR
(300 MHz) δ 7.41 (d, J ) 8.7 Hz, 2H), 6.89 (d, J ) 8.7 Hz, 2H),
5.39 (s, 1H), 5.26 (s, 1H), 4.52 (d, J ) 3.9 Hz, 2H), 3.82 (s, 3H),
1.60 (d, J ) 3.9 Hz, 1H); 13C NMR (75 MHz) δ 159.4, 146.5, 127.2,
113.9, 111.1, 65.2, 55.3; mp 75-77 °C (lit.18 mp 76-78 °C);
HRMS calcd for C14H13O2 (M + H)+ 165.0916, found 165.0910.
2-(4-F lu or op h en yl)-2-p r op en -1-ol (14). Silane 13 (107 mg,
0.42 mmol) gave 14 as a white solid (36 mg, 0.24 mmol, 56%
yield): IR (thin film) 3317, 1715, 1632, 1602, 1043 cm-1; 1H NMR
(300 MHz) δ 7.42 (dd, J ) 5.4, 9.0 Hz, 2H), 7.06 (dd, J ) 8.8, 9.0
3-(Isop r op oxyd im et h ylsilyl)-2-(4-m et h oxyp h en yl)p r o-
p en e (10). Ester 9 (482 mg, 2.9 mmol) gave 10 (744 mg, 2.82
mmol, 97%): IR (neat) 3084, 3040, 2970, 2837, 1610, 1512, 1029
1
cm-1; H NMR (300 MHz) δ 7.36 (d, J ) 9.0 Hz, 2H), 6.84 (d, J
) 8.7 Hz, 2H), 5.10 (s, 1H), 4.86 (s, 1H), 3.96 (m, J ) 6.0 Hz,
1H), 3.81 (s, 3H), 2.08 (s, 2H), 1.11 (d, J ) 6.0 Hz, 6H), 0.00 (s,
6H); 13C NMR (75 MHz) δ 158.9, 144.7, 135.0, 113.4, 109.5, 102.8,
65.0, 55.2, 26.3, 25.7, -1.4; HRMS calcd for C15H24O2Si (M+)
Hz, 2H), 5.42 (s, 1H), 5.33 (s, 1H), 4.51 (s, 2H), 1.72 (s, 1H); 13
C
264.1546, found 264.1547, calcd for
265.1624, found 265.1618.
C
15H25O2Si (M + H)+
NMR (75 MHz) δ 146.2, 134.5, 127.8, 127.7, 115.5, 115.2, 112.7,
65.1; mp 29-30 °C; HRMS calcd for C9H14FON (M + NH4)+
170.0981, found 170.0988.
2-(4-F lu or op h e n yl)-3-(isop r op oxyd im e t h ylsilyl)p r o-
p en e (13). Ester 12 (252 mg, 1.8 mmol) gave 13 (0.35 g, 1.4
mmol, 77% yield, 12:1 mixture with disiloxane). An analytical
sample was obtained by preparative TLC: IR (neat) 3084, 2971,
3-(Hyd r oxym eth yl)-1-p h en yl-1,3-bu ta d ien e (17). Silane
16 (100 mg, 0.38 mmol) gave 17 as a white solid (51 mg, 0.39
mmol, 82% yield): IR (thin film) 3412, 1640, 1448 cm-1; 1H NMR
(300 MHz) δ 7.43 (dd, J ) 1.3, 8.0 Hz, 2H), 7.34 (dt, J ) 1.5, 6.8
Hz, 2H), 7.25 (m, 1H), 7.24 (m, 1H), 6.82 (d, J ) 16.5 Hz, 1H),
6.67 (d, J ) 16.5 Hz, 1H), 5.36 (s, 1H), 5.29 (s, 1H), 4.47 (d, J )
4 Hz, 2H), 1.57 (m, 1H); 13C NMR (75 MHz) δ 145.1, 128.9, 128.7,
128.2, 127.8, 126.5, 120.5, 116.3, 63.3; mp 78-80 °C; HRMS calcd
1
2930, 2875, 1617, 1603, 1028 cm-1; H NMR (300 MHz) δ 7.40
(dd, J ) 5.4, 9.0 Hz, 2H), 6.98 (dd, J ) 8.7, 9.0 Hz, 2H), 5.11 (d,
J ) 1.5 Hz, 1H), 4.92 (d, J ) 0.9 Hz, 1H), 3.94 (septet, J ) 6 Hz,
1H), 2.08 (s, 2H), 1.04 (d, J ) 6 Hz, 6H), 0.00 (s, 6H); 13C NMR
(75 MHz) δ 144.5, 138.6, 127.9, 114.8, 110.9, 102.9, 65.1, 26.6,
25.7, -1.4; HRMS calcd for C14H22OSiF (M + H)+ 253.1424,
found 253.1413.
for C11H13O (M + H)+ 161.0966, found 161.0961, calcd for C11H16
-
NO (M + NH4)+ 178.1232, found 178.1228.
(E)-3-[(Isop r op oxyd im et h ylsilyl)m et h yl]-1-p h en yl-1,3-
bu ta d ien e (16). Ester 15 (454 mg, 2.8 mmol) gave 16 (668 mg,
2-(Hyd r oxym eth yl)-4-p h en yl-1-bu ten -3-yn e (20). Silane
19 (100 mg, 0.39 mmol) gave 20 as a colorless oil (40 mg, 0.25
2.57 mmol, 92% yield): IR (neat) 3027, 2969, 1596, 1026 cm-1
;
mmol, 65% yield): IR (neat) 3401, 2203, 1645, 1058 cm-1 1H
;
1H NMR (300 MHz) δ 7.41 (d, J ) 7.4 Hz, 2H) 7.31 (t, J ) 7.4
Hz, 2H), 7.21 (m, 1H), 6.86 (d, J ) 16.2 Hz, 1H), 6.60 (d, J )
16.2 Hz, 1H), 5.11 (s, 1H), 4.98 (s, 1H), 4.04 (dt, J ) 6.0 , 0.6
Hz, 1H), 1.97(s, 2H), 1.16 (d, J ) 6.2 Hz, 6H), 0.14 (s, 6H); 13C
NMR (75 MHz) δ 143.1, 137.4, 131.9, 129.0, 128.7, 128.6, 127.7,
NMR (300 MHz) δ 7.45-7.48 (m, 2H), 7.31-7.35 (m, 3H), 5.61
(d, J ) 1.8 Hz, 1H), 5.58 (d, J ) 1.5 Hz, 1H), 4.25 (s, 2H), 1.80
(br s, 1H); 13C NMR (75 MHz) δ 131.7, 131.2, 128.5, 128.3, 122.7,
120.5, 90.9, 86.9, 65.4; HRMS calcd for C11H11O (M + H)+
159.0810, found 159.0808, calcd for C11H14NO (M + NH4)+
176.1075, found 176.1079.
126.7, 126.5, 115.7, 65.2, 25.8, 22.6, -1.2; HRMS calcd for C16H24
-
OSi (M + H)+ 261.1676, found 261.1673.
2-[(Isop r op oxyd im eth ylsilyl)m eth yl]-4-p h en yl-1-bu ten -
Ack n ow led gm en t. We thank Pfizer Central Re-
search, Groton, CT for support of this work through a
Pfizer Undergraduate Research Fellowship in Synthetic
Organic Chemistry awarded to T.J.M. We also acknowl-
edge support from the University of Minnesota’s Gradu-
ate School Grant-In-Aid (16163), Undergraduate
Research Opportunity, and McKnight Land-Grant Pro-
fessorship (C.J .F.) programs.
3-yn e (19). Ester 18 (448 mg, 2.8 mmol) gave 19 (686 mg, 2.66
mmol, 95%): IR (neat) 3085, 1600, 1490, 1028 cm-1 1H NMR
;
(300 MHz) δ 7.43 (m, 2H), 7.31 (m, 2H), 5.32 (d, J ) 1.8 Hz,
1H), 5.17 (d, J ) 1.8 Hz, 1H), 4.07 (septet J ) 6.0 Hz, 1H), 1.89
(s, 2H), 1.16 (d, J ) 6.0 Hz, 6H), 0.25 (s, 6H); 13C (75 MHz)
131.42, 128.26, 128.06, 127.79, 123.37, 120.00, 91.36, 88.45,
65.16, 28.48, 25.81, -1.39; HRMS calcd for C16H23OSi (M + H)+
259.1518, found 259.1526.
Allylic Alcoh ols 8, 11, 14, 17, a n d 20. Treatment of allylic
silanes 7, 10, 13, 16, and 19 with KHCO3 (4 equiv), KF‚2H2O (8
equiv), and 30% H2O2 (4.8 equiv) under the conditions described
for the preparation of 4 above gave, after workup and chroma-
tography, allylic alcohols 8, 11, 14, 17, and 20, respectively.
2-P h en yl-2-p r op en -1-ol (8). Silane 7 (55 mg, 0.23 mmol)
gave 8 as a colorless oil (26 mg, 0.19 mmol, 84% yield): IR (neat)
3372, 1631, 1599, 1047, 1026 cm-1; 1H NMR (300 MHz) δ 7.43-
7.48 (m, 2H), 7.26-7.39 (m, 3H), 5.48 (s, 1H), 5.36 (s, 1H), 4.56
(s, 2H), 1.62 (br s, 1H); 13C NMR (75 MHz) δ 142.3, 138.5, 128.5,
128.0, 126.1, 112.6, 65.1; HRMS calcd for C9H14ON (M + NH4)+
152.1075, found 152.1078.
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra of compounds (R)-3, (R)-4, (R,R)-5, and (S,R)-5 and H
NMR spectra of compounds 7, 8, 10, 11, 13, 14, 16, 17, 19,
and 20 (15 pages). This material is contained in libraries on
microfiche, immediatley follows this article in the microfilm
version of the journal, and can be ordered from the ACS; see
any current masthead page for ordering information.
1
J O961639H
(18) Kirmse, W.; Rode, J . Chem. Ber. 1986, 119, 3694-3703.