Terminal Alkyne-Ethylene Cross-Metathesis: Reaction of 1-Substituted Propargyl Esters at Elevated Ethylene Pressure

Article abstract of DOI:10.1021/jo9916941

Substituted propargylic esters, resistant to complete ethylene cross-metathesis at ambient pressure, underwent cross-metathesis with ethylene at elevated pressure (4 atm) to give 2-substituted butadienes in good to excellent yields. Enantioenriched propargylic acetates, obtained through enzymatic kinetic resolution of secondary propargyl alcohols, similarly underwent ethylene metathesis with retention of stereochemistry at the chiral center.

Full text of DOI:10.1021/jo9916941

1788
J . Org. Chem. 2000, 65, 1788-1792
Ter m in a l Alk yn e-Eth ylen e Cr oss-Meta th esis: Rea ction of
1-Su bstitu ted P r op a r gyl Ester s a t Eleva ted Eth ylen e P r essu r e
J ason A. Smulik and Steven T. Diver*
Department of Chemistry, State University of New York, Buffalo, New York 14260-3000
Received October 28, 1999
Substituted propargylic esters, resistant to complete ethylene cross-metathesis at ambient pressure,
underwent cross-metathesis with ethylene at elevated pressure (4 atm) to give 2-substituted
butadienes in good to excellent yields. Enantioenriched propargylic acetates, obtained through
enzymatic kinetic resolution of secondary propargyl alcohols, similarly underwent ethylene
metathesis with retention of stereochemistry at the chiral center.
In the context of synthetic studies directed toward the
and synthetic studies.6 Notable attributes of the well-
defined catalysts of Grubbs7 and Schrock8 include func-
tional group tolerance, low catalyst loadings, alkene
chemoselection, and commercial availability. These fea-
tures have helped metathesis become a prominent syn-
thetic method. Intramolecular examples of alkyne-
alkene metathesis were documented by Katz and Sivavec9
and the Grubbs group10 to form carbocycles and fused
carbobicyclic ring systems, respectively. It is significant
to note that this catalytically efficient process is atom
economical. Kinoshita, Mori, and co-workers developed
the specific case of ethylene-alkyne metathesis,11 which
was used in natural product synthesis.12 Blechert has
explored the intermolecular reaction of terminal alkynes
with excess R-olefins in an example of ene-yne cross-
metathesis using the Grubbs benzylidene catalyst 1.13 In
a recent publication, Mori has outlined the scope of
ethylene-alkyne metathesis at 1 atm ethylene and
provided one example of ethylene metathesis in an alkyl-
substituted propargylic carbonate.14 The dienes that
result from ene-yne cross-metathesis (and a related Ru-
catalyzed process15) are generally useful and have been
employed in Diels-Alder reactions.11,13,15
UCT4B1 side chain, we required an enantioselective
synthesis of enantiopure dienyl alcohols. Although there
are several methods available to introduce the butadiene
fragment, an enantioselective process that could be used
with a variety of aldehydes was required. Existing
methods for the direct introduction of the butadienyl
fragment lack scope and further either lack enantiose-
lection (homoallenyltrimethylsilane, TiCl4;2 homoallenyl-
tributylstannane; and Lewis acid3) or require long reac-
tion times at low temperature (diisopropylhomoallenyl-
boronate, diethyl tartrate, -78 °C, 72 h).4 The latter
method was elegantly employed by Theodorakis in his
synthesis of clerocidin.5 For our studies, we required a
practical multigram-scale reaction suitable for use with
a variety of aromatic and aliphatic aldehydes. We report
here an ethylene-alkyne metathesis (eq 1) that tolerates
propargylic substitution and proves to be an efficient
diene synthesis. The significance of higher ethylene
pressure and the use of ethylene metathesis with enan-
tiopure alkynes to prepare enantiomerically enriched
2-substituted butadienes are also reported.
Our preparation of racemic dienyl acetates is sum-
marized in eq 1 (above). The diene fragment is introduced
in three steps from aldehydes: addition of HCtC-MgBr,
protection of the alcohol, and ethylene-alkyne metath-
esis. The Grignard addition occurred in high yield (93%
for PhCHO) and protection utilized standard conditions
(6) Reviews: (a) Grubbs, R. H.; Chang, S. Tetrahedron 1998, 54,
4413. (b) Grubbs, R. H.; Miller, S. J .; Fu, G. C. Acc. Chem. Res. 1995,
28, 446.
(7) Schwab, P.; Grubbs, R. H.; Ziller, J . W. J . Am. Chem. Soc. 1996,
118, 100.
(8) Schrock, R. R.; Murdzek, J . S.; Bazan, G. C.; Robbins, J .; DiMare,
M.; O’Regan, M. J . Am. Chem. Soc. 1990, 112, 3875.
(9) Katz, T. J .; Sivavec, T. M. J . Am. Chem. Soc. 1985, 107, 737.
(10) Kim, S.-H.; Bowden, N.; Grubbs, R. H. J . Am. Chem. Soc. 1994,
116, 10801.
(11) Kinoshita, A.; Sakakibara, N.; Mori, M. J . Am. Chem. Soc. 1997,
119, 12388.
(12) (a) Mori, M.; Sakakibara, N.; Kinoshita, A. J . Org. Chem. 1998,
63, 6082. (b) Kinoshita, A.; Mori, M. J . Org. Chem. 1996, 61, 8356.
(13) Stragies, R.; Schuster, M.; Blechert, S. Angew. Chem., Int. Ed.
Engl. 1997, 36, 2518.
Over the past few years, there has been tremendous
application of metathesis to natural product synthesis
(1) Kawada, S. Z.; Yamashita, Y.; Uosaki, Y.; Gomi, K.; Iwasaki,
T.; Takiguchi, T.; Nakano, H. J . Antibiot. (Tokyo) 1992, 45, 1182.
(2) (a) Hatakeyama, S.; Yoshida, M.; Esumi, T.; Iwabuchi, Y.; Irie,
H.; Kawamoto, T.; Yamada, H.; Nishizawa, M. Tetrahedron Lett. 1997,
38, 7887. (b) Hatakeyama, S.; Sugawara, K.; Kawamura, M.; Takano,
S. Tetrahedron Lett. 1991, 32, 4509.
(3) (a) Luo, M.; Iwabuchi, Y.; Hatakeyama, S. Synlett 1999, 1109.
(b) Luo, M.; Iwabuchi, Y.; Hatakeyama, S. Chem. Commun. (Cam-
bridge) 1999, 267.
(14) The substituted alkyne requires longer reaction times (50 h)
at 1 atm of ethylene to obtain 87% conversion and 73% isolated yield;
see: Kinoshita, A.; Sakakibara, N.; Mori, M. Tetrahedron 1999, 55,
8155.
(4) Soundararajan, R.; Li, G.; Brown, H. C. J . Org. Chem. 1996, 61,
100.
(5) Xiang, A. X.; Watson, D. A.; Ling, T.; Theodorakis, E. A. J . Org.
Chem. 1998, 63, 6774.
(15) Trost, B. M.; Pinkerton, A. B. J . Am. Chem. Soc. 1999, 121,
4068.
10.1021/jo9916941 CCC: $19.00 © 2000 American Chemical Society
Published on Web 02/18/2000

Terminal Alkyne-Ethylene Cross-Metathesis
J . Org. Chem., Vol. 65, No. 6, 2000 1789
Ta ble 1. Effect of Eth ylen e P r essu r e a n d Ca ta lyst
Loa d in g
entry
1
conditions
5 mol % 1
isolated yield (%)
38
1 atm (balloon), 29 h
5 mol % 1
60 psi, 22 h
1 mol % 1
60 psi, 22 h
1 mol % 1
2
3
4
78
44
78
95 psi, 59 h
for acetylation (1.25 equiv of Ac2O, 3 equiv of Et3N,
DMAP (cat.) in DCM, 99% for acetate 2) to produce the
metathesis substrates. Metathesis was conducted with
Grubbs’ catalyst 1 and ethylene pressure to provide the
substituted dienes.
F igu r e 1. Conversion of 2 to 3 as a function of time.
circulating water bath. The initial concentration of alkyne
was 0.2 M, similar to the reaction conditions presented
in Table 2 below. Small variations in the rate were noted
when aliquots were taken for analysis at frequent
intervals. From these conversion data, it can be seen that
balloon ethylene pressure is not sufficient to drive the
metathesis to completion.17 However, a modest increase
in ethylene pressure can be used to overcome the rate
and yield limitation, which may increase the alkyne
substrate scope of the ethylene-alkyne metathesis.
The higher solution concentration of ethylene at 60 psi
can be used to explain the observed rate increase. The
concentration of ethylene in CD2Cl2 was measured versus
toluene concentration (internal standard) under balloon
pressure and at 60 psi in a 5 mm NMR tube equipped
with a Teflon valve. At balloon pressure, the ethylene
concentration was found to be 32 mM. At 60 psi, the
ethylene concentration was 690 mM, or ca. 20 times more
concentrated than at atmospheric pressure. A similar
difference in solution concentration of ethylene was found
in CDCl3.
The results of ethylene-alkyne metathesis with 1-acy-
loxy-1-substituted propynes are shown in Table 2. The
reaction conditions of Table 2 employ 0.12 M alkyne in
dichloromethane solvent and 5 mol % 1 held at 60 psi
(4.1 atm) of ethylene in a pressure bottle for 22 h.
Elevated temperatures were not explored due to the
reported instability of active catalyst 16 (Scheme 1).7 The
reactions proved very clean, producing the diene and a
trace of styrene as a byproduct. Dimers arising from the
produced 1,3-dienes were not detected in the crude
reactions as determined by GC-MS analysis. The prod-
ucts in Table 2 were isolated as colorless compounds after
preparative layer or column chromatography, free of
ruthenium catalyst byproducts. In contrast with litera-
ture examples,11-13 substitution at the propargylic posi-
tion was well-tolerated at elevated ethylene pressure.
Entry 3 suggests that good yields are possible in hindered
systems using the standard conditions of Table 2.
Higher ethylene pressures resulted in better chemical
yields and shorter reaction times for complete conversion
of alkynes. Initial studies were performed with RNpCH-
(OTBS)CtCH using the standard literature conditions
(1 atm of ethylene, 5 mol % of 1). In this case, no
conversion to the diene was apparent after 24 h. How-
ever, when ethylene pressure was increased to 60 psi,
12% conversion to diene occurred (GC analysis) after 16
h. With these contrasting data at different ethylene
pressures, a less sterically bulky protecting group was
sought for the substituted propargyl alcohol. Acyl groups
were chosen for this purpose. Optimization studies were
conducted with the acetyl group in the conversion of 2 to
3, as summarized in eq 2 (Table 1). Metathesis conducted
using literature conditions with 1 atm of ethylene at room
temperature gave some conversion of 2 f 3 with a low
chemical yield (entry 1). At 1 atm of ethylene, the
conversion leveled off near 60% 3 after 40 h (analytical
GLPC). Higher conversions were attained using slightly
elevated ethylene pressure. In examples conducted at
50-60 psi, conversions were usually >95% (GC-MS)
with isolated yields lower, possibly due to diene decom-
position during isolation.16 The effect of catalyst loading
was also explored with 2 (entries 3 and 4). From the
literature, typical catalyst loading is 5-10 mol %. It was
found that low (1 mol %) loading gave inferior results
after 22 h (entry 3); however, longer reaction time at 95
psi of ethylene produced an improved yield of 3 (44% to
78%), making 1 mol % loading feasible. This last result
suggests that the catalyst is still viable after 22 h. It is
speculated that higher ethylene pressure may also help
avert catalyst decomposition pathways.12a
The rate of conversion of alkyne 2 to diene 3 at balloon
ethylene pressure and at 60 psi of ethylene pressure
illustrates the effect of higher pressure on conversion
(Figure 1). Conversion to product was monitored over
time (to 50 h) using a quantitative GLPC method. Each
of the reactions was vigorously stirred in a 90 mL
capacity vessel maintained at 15 °C using a thermostated
(17) The reaction conducted at 1 atm continued to convert to product
3 even after 50 h, but only reached 68% 3 after 95 h. The data taken
after ca. 50 h are not considered reliable since evaporative loss of
solvent became significant at 1 atm of pressure (balloon). Evaporative
loss of solvent was not serious at higher pressures or shorter reaction
times.
(16) For instance, storage of 11 at -20 °C for a period of 1 week
resulted in discoloration and minor but detectable decomposition by
1H NMR.

1790 J . Org. Chem., Vol. 65, No. 6, 2000
Smulik and Diver
Ta ble 2. Resu lts of Eth ylen e-Alk yn e Meta th esisa
Sch em e 1
likewise be shifted toward 18 due to mass action (17 +
excess CH2dCH2 f 18). Even higher ethylene pressures
(99.5% ethylene, 500 psi) did not further improve reaction
rate or conversion (70% conversion after 14 h). It is
conceivable that higher ethylene pressure results in an
unproductive equilibrium (CH2dCH2 + 16 ) 19) that
depletes the concentration of active catalyst 16 (Scheme
1). To achieve high conversions at reasonable (5 mol %)
catalyst loadings, 50-60 psi of ethylene maintained in a
pressure bottle proved sufficient and was experimentally
convenient. For large-scale reactions, lower catalyst
loading can be used in conjunction with longer reaction
times, as noted in Table 1.
By coupling the present method with enantioselective
synthesis, it is possible to obtain enantiomerically en-
riched dienyl acetates. The dienyl acetates were obtained
by subjecting enantioenriched alkynyl acetates to ethyl-
ene metathesis (Scheme 2). Several chemical methods are
available for preparing scalemic alkynols;18 however, a
simple kinetic resolution of readily available rac-20 using
cross-linked enzyme crystals (CLECs) of Pseudomonas
cepacia (Altus) proved efficient and convenient. Alcohol
20 was resolved as shown in eq 3. From this reaction,
the selectivity factor was calculated and the enantiomeric
preference of the enzyme was verified by measuring the
specific rotation of the products (S)-20 and (R)-2 (eq 3).19
Higher enantiomeric excess of recovered alcohol S-20 was
obtained by running the resolution to higher conversion
(see the Experimental Section). In a separate batch, (S)-
20 (>99% ee, 34% isolated yield from rac-20) was
acetylated to give (S)-2 (>99% ee, HPLC), which was
subjected to ethylene metathesis at 60 psi to afford the
diene (S)-3 in 80% yield of >95% ee (eq 4). Due to minor
(<1%, analytical GLPC) contamination by unreacted (S)-
2, (S)-3 was saponified and determined to have >95% ee
by HPLC. The fact that the acetates 2 and 3 resist
racemization by methylidene 16 attests to the mild Lewis
acidic nature of the Grubbs-type catalysts.
a
Conditions: 5 mol % 1, ethylene (60 psi), DCM, rt, 22 h. The
reaction conditions were optimized for the conversion of 2 to 3.
The propargylic alcohol protecting group influenced the
reaction. In the cases examined (Table 2), acyl protecting
groups proved to be the best, with the acetate and
benzoate giving similar results (cf. entries 1, 2 and entries
5, 6). Alkyl ethers were not investigated. With R-aryl
substituents, the TBS protecting group was too bulky:
RNpCH(OTBS)CtCH was only 12% converted to the
diene after 16 h at 60 psi of ethylene as determined by
GC-MS analysis. The free alcohols RNpCH(OH)CtCH
and PhCH(OH)CtCH underwent lower conversions and
did not give synthetically useful yields under the normal
conditions of Table 2.
Ethylene plays a dual role in ethylene-alkyne me-
tathesis (Scheme 1). Ethylene is used to generate an
active methylidene catalyst and is consumed stoichio-
metrically as a reactant. Exposure of the catalyst 1 to
ethylene leads to the formation of the methylidene 16.7
In an intramolecular ene-yne metathesis that does not
incorporate ethylene, Mori has suggested that 1 atm
ethylene protects the catalyst 16 from a thermodynamic
sink (e.g., 17).12a In the present case, since 17 occurs in
the catalytic cycle, it may be inferred that its conversion
to ruthenacycle 18 is rate-limiting. Steric bulk at the
propargylic position might further slow this step in the
catalytic cycle. Higher ethylene pressure would be ex-
pected to have an accelerating effect due to increased
concentration, as noted above. The equilibrium would
In conclusion, it has been shown that R-substituted
propargyl alcohol derivatives undergo efficient cross-
(18) (a) Midland, M. M. Chem. Rev. 1989, 89, 1553. (b) Corey, E. J .;
Cimprich, K. A. J . Am. Chem. Soc. 1994, 116, 3151.(c) Parker, K. A.;
Ledeboer, M. W. J . Org. Chem. 1996, 61, 3214. (d) Corey, E. J .; Helal,
C. J . Angew. Chem., Int. Ed. Engl. 1998, 37, 1986.
(19) Use of related lipases: (a) Viola, A.; Duddling, G. F.; Proverb,
R. J . J . Am. Chem. Soc. 1977, 99, 7390. (b) Kuenstler, T.; Schollmeyer,
D.; Singer, H.; Steigerwald, M. Tetrahedron: Asymmetry 1993, 4, 1645.
(c) Glaenzer, B. I.; Faber, K.; Griengl, H. Tetrahedron 1987, 43, 5791.
(d) Waldinger, C.; Schneider, M.; Botta, M.; Corelli, F.; Summa, V.
Tetrahedron: Asymmetry 1996, 7, 1485. (e) Enantioselectivity model:
Burgess, K. B.; J ennings, L. D. J . Am. Chem. Soc. 1991, 113, 6129.

Terminal Alkyne-Ethylene Cross-Metathesis
J . Org. Chem., Vol. 65, No. 6, 2000 1791
Sch em e 2
2-(1-Acetoxy-1-(p h en yl)m eth yl)-1,3-bu ta d ien e 3 (En tr y
1). Obtained in 78% yield after 22 h at 60 psi of ethylene: 1H
NMR (300 MHz, CDCl3, ppm) δ 7.40-7.30 (m, 5H), 6.56 (s,
1H), 6.30 (dd, J ) 17.7, 11.1 Hz, 1H), 5.35 (s, 1H), 5.34 (s,
1H), 5.23 (d, J ) 17.7 Hz, 1H), 5.06 (d, J ) 11.1 Hz, 1H) 2.11
(s, 3H); 13C NMR (75 MHz, CDCl3, ppm) d 169.8, 144.2, 138.3,
135.4, 128.4, 128.2, 127.6, 116.6, 115.7, 24.4, 21.1; High-
resolution MS (EI+) molecular ion calcd for C13H14O2 202.0994,
found 202.0987, error 3.3 ppm; low-resolution FAB-MS 225.1
(M + Na).
metathesis with ethylene at slightly elevated pressure
to afford 2-substituted butadienes. Higher ethylene pres-
sure proved crucial to obtain high conversions to diene
products. Enantiomerically enriched alkynes undergo
ethylene metathesis with retention of configuration at
the propargylic/allylic center, making this method suit-
able for preparing enantiomerically enriched dienes. This
method is currently being used to prepare the side chain
of UCT4B.
2-(1-Ben zoyloxy-1-(ph en yl)m eth yl)-1,3-bu tadien e 5 (En -
tr y 2). Obtained in 80% yield after 22 h at 60 psi of ethylene:
1H NMR (300 MHz, CDCl3, ppm) δ 8.11-7.30 (m, 8H), 8.09
(m, 2H), 6.81 (s, 1H), 6.36 (dd, J ) 17.7, 11.1 Hz, 1H), 5.43 (s,
1H), 5.39 (s, 1H), 5.31 (d, J ) 17.7 Hz, 1H), 5.10 (d, J ) 11.1
Hz, 1H); 13C NMR (75 MHz, CDCl3, ppm) δ 165.4, 144.3, 138.4,
135.4, 133.1, 130.1, 129.7, 128.5, 128.4, 128.2, 127.5, 116.9,
115.9, 75.1; high-resolution MS (EI+) molecular ion calcd for
Exp er im en ta l Section
Gen er a l Meth od s. Reactions were conducted under argon
atmosphere unless otherwise noted. Dichloromethane (DCM)
was distilled from CaH2 immediately prior to use. Aldehydes
were washed successively with Na2CO3, H2O, and brine, dried
(MgSO4), and distilled. Ethynylmagnesium bromide (0.5 M in
THF) was purchased from Aldrich. The Grubbs catalyst, bis-
(tricyclohexylphosphine)benzylidene ruthenium (IV) dichlo-
ride, was purchased from Strem. Ethylene (CP grade, 99.5%,
Matheson) was used from either a lecture bottle or a 13 kg
capacity cylinder equipped with the appropriate regulator.
ChiroCLEC PC (dry) was obtained from Altus Biologics.
Reactions were conducted in oven-dried 90 mL capacity
pressure tube equipped with a gas inlet, pressure gauge, and
relief valve. 1H NMR and 13C NMR were recorded in CDCl3 at
C
18H16O2 264.1150, found 264.1133, error 6.6 ppm; low-
resolution FAB-MS (NBA/NaI) 287.4 (M + Na).
2-(1-Acetoxy-1-(R-n aph th yl)m eth yl)-1,3-bu tadien e 7 (En -
tr y 3). Obtained in 75% yield after 22 h at 60 psi of ethylene:
1H NMR (300 MHz, CDCl3, ppm) δ 8.04 (d, J ) 7.8 Hz, 1H),
7.91-7.83 (m, 2H), 7.60-7.38 (m, 4H), 6.44 (dd, J ) 18.0, 11.4
Hz, 1H), 5.44 (br s, 1H), 5.25 (br s, 1H), 5.19 (d, J ) 18.0 Hz,
1H), 5.09 (d, J ) 11.4 Hz, 1H), 2.18 (s, 3H); 13C NMR (75 MHz,
CDCl3, ppm) δ 170.05, 144.14, 135.94, 133.84, 133.67, 131.14,
129.15, 128.84, 126.59, 125.79, 125.58, 125.22, 123.22, 117.90,
114.44, 70.58, 21.06; high-resolution MS (EI+) molecular ion
calcd for C17H16O2 252.1150, found 252.1170, error 8 ppm; low-
resolution FAB-MS (NBA/NaI) 275.4 (M + Na), 193.3 (M -
59).
1
the indicated frequency. H NMR spectra were referenced at
7.24 ppm on the residual CHCl3 signal, and 13C NMR were
referenced at 77.0 ppm for CDCl3. Optical rotations were
measured using the sodium D line in a thermostated cell held
at 23 °C. Enantiomeric excesses were determined by HPLC
using conditions A (R,R-Whelk-O1 column, 2.5% IPA-hexanes,
1.0 mL/min, UV-254), conditions B (Chiracel OD column, 10%
IPA-hex, 0.5 mL/min, UV-254), or by GC using a chiraldex-B
capillary column (40-200 °C over 20 min, J & W Scientific,
0.25 mm × 30 m, 0.25 mm film thickness). Quantitative GLPC
was obtained using a DB-wax capillary column (J & W
Scientific, 0.25 mm × 30 m, 0.25 mm film thickness) calibrated
with known standards.
2-(1-Ben zoyloxy-1-m eth yl)-1,3-bu ta d ien e 9 (En tr y 4).
Obtained in 92% yield after 22 h at 60 psi of ethylene: 1H
NMR (300 MHz, CDCl3, ppm) δ 8.08 (br d, J ) 6.9 Hz, 1H),
7.56 (m, 2H), 7.44 (m, 2H), 6.38 (dd, J ) 18.0, 11.1 Hz, 1H),
5.86 (q, J ) 6.6 Hz, 1H), 5.41 (d, J ) 18.0 Hz, 1H), 5.34 (br s,
1H), 5.20 (br s, 1H), 5.17 (d, J ) 11.1 Hz, 1H), 1.58 (d, J ) 6.6
Hz, 3H); 13C NMR (75 MHz, CDCl3, ppm) δ 165.68, 146.49,
135.73, 132.9, 130.48, 129.59, 128.34, 114.87, 114.74, 70.0,
20.29; high-resolution MS (EI+) molecular ion calcd for C13H14O2
202.0994, found 202.0984, error 5 ppm.
2-(1-Acetoxy-3-(p h en yl)p r op yl)-1,3-bu ta d ien e 11 (En -
tr y 5). Obtained in 64% yield after 22 h at 60 psi of ethylene.
1H NMR (500 MHz, CDCl3, ppm) δ 7.27 (m, 2H), 7.17 (m, 3H),
6.30 (dd, J ) 18.0, 11.5 Hz, 1H), 5.50 (t, J ) 6.5 Hz, 1H), 5.25
(d, J ) 17.5 Hz, 1H), 5.19 (br s, 1H), 5.17 (br s, 1H), 5.09 (d, J
) 11.0 Hz, 1H), 2.65 (m, 2H), 2.06 (s, 3H), 2.03 (m, 2H). 13C
NMR (125 MHz, CDCl3, ppm) d 170.1, 145.1, 135.5, 128.4,
128.3, 125.9, 115.2, 114.7, 72.6, 35.6,31.8, 21.0; low-resolution
FAB-MS (NBA/NaI) molecular ion calcd for C15H18O2Na 253.3,
found 253.3 (M + Na).
Gen er a l P r oced u r e for Eth ylen e-Yn e Meta th esis:
2-(1-Acetoxy-1-p h en ylm eth yl)-1,3-bu ta d ien e 3. Into an
oven-dried pressure tube (90 mL capacity) equipped with
magnetic stirbar was added 26 mg of bis(tricyclohexylphos-
phine)benzylidene ruthenium(IV) dichloride (31.9 mmol, 5 mol
%) under argon. A solution of 111 mg of 1-acetoxy-1-phenyl-
2-propyne 2 (0.63 mmol) in 4.0 mL of DCM was added to the
catalyst via syringe, and the vessel was pressurized to 60 psi
of ethylene (CP grade, 99.5%) under rapid stirring. The
pressure was released and the vessel subsequently flushed four
times and then maintained at 60 psi of ethylene for 22 h. The
pressure was released, and the solvent was removed in vacuo
(rotary evaporator) to afford a dark brown oil that was purified
by flash chromatography (4 in. column, elution with 1:10 ethyl
acetate (EA)-hexane) to give 3 as a clear oil, 100 mg, 78%
yield. Analytical TLC: Rf 0.44 (1:4 EA-hexanes).
2-(1-Ben zoyloxy-3-(ph en yl)pr opyl)-1,3-bu tadien e 13 (En -
tr y 6). Obtained in 57% yield after 22 h at 60 psi of ethylene:
1H NMR (500 MHz, CDCl3, ppm) δ 8.07 (br d, J ) 7.5 Hz, 2H),
7.56 (m, 1H), 7.44 (m, 2H), 7.26 (m, 2H), 7.18 (m, 3H), 6.36

1792 J . Org. Chem., Vol. 65, No. 6, 2000
Smulik and Diver
(dd, J ) 17.5, 11.0 Hz, 1H), 5.76 (dd, J ) 7.0, 5.5 Hz, 1H),
5.33 (d, J ) 18.0 Hz, 1H), 5.28 (br s, 1H), 5.20 (br s, 1H), 5.13
(d, J ) 11.5 Hz, 1H), 2.75 (m, 2H), 2.19 (m, 2H); 13C NMR
(125 MHz, CDCl3, ppm) δ 165.6, 145.1, 141.2, 135.5, 132.9,
130.3, 129.5, 128.4, 128.3, 125.9, 115.4, 114.8, 73.3, 35.8, 31.8;
low-resolution FAB-MS (NBA/NaI) calcd for C20H20O2Na 315.1,
found 315.1 (M + Na).
2-(1-Acetoxy-2-(R-n aph th yl)eth yl)-1,3-bu tadien e 15 (En -
tr y 10). Obtained in 78% yield after 22 h at 60 psi of
ethylene: 1H NMR (500 MHz, CDCl3, ppm) δ 8.14 (br d, J )
9.0 Hz, 1H). 7.84 (br d, J ) 8.0 Hz, 1H), 7.73 (br d, J ) 8.0
Hz,1H), 7.53 (m, 1H), 7.47 (m, 1H), 7.37 (m, 1H), 7.31 (br d, J
) 6.5 Hz, 1H), 6.36 (dd, J ) 18.0, 11.0 Hz, 1H), 5.83 (dd, J )
8.0, 6.0 Hz, 1H), 5.44 (d, J ) 18.0 Hz, 1H), 5.17 (br s, 1H),
with hexane to 1:3 EA-hexane) to give 534 mg of (R)-2 (3.07
mmol, 49% yield, 89.8% ee (HPLC), [R]589 ) +4 (c ) 3.05,
CHCl3)) and 368 mg of (S)-20 (2.79 mmol, 45% yield, 90% ee
(HPLC), [R]589 ) +22 (c ) 3.3, CHCl3)). The enantioselectivity
factor E ) 58 based on 50% conversion.
La r ge-Sca le En zym a tic Resolu tion of Alk yn ol 20. Into
a 200 mL round-bottom flask equipped with magnetic stirbar
was placed 5.5 g of rac-20 (41.6 mmol, 1.0 equiv) and 5.75 mL
of vinyl acetate (5.37 g, 62.5 mmol, 1.5 equiv) in 100 mL of
toluene containing 30 µL of H2O. To the rapidly stirred solution
was added 30 mg of ChiroCLEC PC (dry), and the reaction
was monitored by GLPC (Chiraldex-B), which showed about
60% conversion (uncorrected for response factor) after 25 h.
The reaction was then filtered through a plug of glass wool,
evaporated in vacuo (rotovap), and chromatographed on silica
gel (12 in. column, gradient elution with hexane to 1:3 EA-
hexane) to give 3.5 g of (R)-2 [20.1 mmol, 48% yield, 83% ee
(GC, chiraldex B), Rf 0.42 (1:4 ether-petroleum ether)] and
2.2 g of (S)-20 [16.6 mmol, 40% yield, 97% ee (GC, Chiraldex-
B), Rf 0.15 (1:4 ether-petroleum ether)].
5.15 (d, J ) 11.0 Hz,1H), 5.13 (br s, 1H), 3.50 (AB q, J AB
14.0 Hz, J AX ) 8.3 Hz, 1H), 3.44 (AB q, J AB ) 14.0 Hz, J BX
)
)
5.9 Hz, 1H), 1.93 (s, 3H); 13C NMR (125 MHz, CDCl3, ppm) δ
170.0, 145.1, 135.5, 133.7, 133.5, 132.2, 128.7, 127.6, 127.4,
125.9, 125.5, 125.2, 123.8, 116.1, 115.1, 73.7, 37.5, 21.0; high-
resolution MS (EI+) molecular ion calcd for C18H18O2 266.1307,
found 266.1281, error 3.2 ppm; low-resolution FAB-MS (NBA/
NaI) 289.4 (M + Na), 207.3 (M - 59).
Ack n ow led gm en t. We express our gratitude to the
National Science Foundation (CHE-9725002), the do-
nors of the Petroleum Research Fund administered by
the ACS, and SUNY Buffalo for financial support of this
work. We also thank Professor J im Atwood for use of
his pressure equipment.
Deter m in a tion of Absolu te Con figu r a tion in En zy-
m a tic Resolu tion of Alk yn ol 20. Into a 50 mL round-bottom
flask equipped with a magnetic stirbar was placed 0.823 g of
rac-20 (6.23 mmol, 1.0 equiv) and 0.86 mL of vinyl acetate (9.35
mmoL, 1.5 equiv) in 20 mL of toluene containing 10 µL of H2O.
To the rapidly stirred solution was added 10 mg of ChiroCLEC
PC (dry), and the reaction was monitored by HPLC (UV-254,
R,R-Whelk-O 1 column, 6% IPA-hexanes, 1.0 mL/min), which
showed about 49% conversion (uncorrected for molar extinction
coefficient) after 6.5 h. The reaction was then filtered through
a plug of glass wool, evaporated in vacuo (rotovap), and
chromatographed on silica gel (6 in. column, gradient elution
Su p p or tin g In for m a tion Ava ila ble: Proton NMR for
dienes 3, 5, 7, 9, 11, 13, and 15. This material is available
free of charge via the Internet at http://pubs.acs.org.
J O9916941