Carbonylation of Alkynyl Epoxides: Synthesis of 5-Hydroxy-2,3-dienoate Esters and 2,3-Dihydrofuran-3-ol Derivatives

Article abstract of DOI:10.1021/jo971303n

The carbonylation of alkynyl oxiranes catalyzed by (MePh₂)₄Pd in the presence of 20 atm of carbon monoxide in methanol gives methyl 5-hydroxy-2,3-pentadienoates in good yields. When the reaction is performed on alkynyl oxiranemethano

Full text of DOI:10.1021/jo971303n

8484
J . Org. Chem. 1997, 62, 8484-8489
Ca r bon yla tion of Alk yn yl Ep oxid es: Syn th esis of
5-Hyd r oxy-2,3-d ien oa te Ester s a n d 2,3-Dih yd r ofu r a n -3-ol
Der iva tives
Marcelo E. Piotti and Howard Alper*
Department of Chemistry, University of Ottawa, 10 Marie Curie, Ottawa, Ontario, Canada K1N 6N5
Received J uly 15, 1997X
The carbonylation of alkynyl oxiranes catalyzed by (MePh2)4Pd in the presence of 20 atm of carbon
monoxide in methanol gives methyl 5-hydroxy-2,3-pentadienoates in good yields. When the reaction
is performed on alkynyl oxiranemethanol derivatives, 4,5-dihydrofuran-3-ol derivatives are obtained
stereoselectively. These products arise from the spontaneous cyclization of a dihydroxyallenyl ester
intermediate.
Sch em e 1
Alkynes containing a leaving group in the propargylic
position are frequently used as substrates for reactions
catalyzed by Pd(0) complexes.1 These reactions involve
the formation of σ-allenyl palladium (II) intermediates,
compounds that have been isolated and characterized.2
Such intermediates can undergo insertion of molecules
such as olefins and carbon monoxide into the C-Pd bond,
or can react with nucleophiles at the central carbon of
the allene moiety (Scheme 1). In this way, several C-C
coupling carbonylation and other reactions of propargylic
compounds have been reported.1
Carbon monoxide inserts readily into the palladium-
carbon bond of a σ-complex, giving an acyl palladium
intermediate, which reacts with an alcohol to form an
allenic carboxylic ester and liberates the Pd(0) complex.
Carbonylation of propargylic carbonates,3 acetates,4a
phosphates,4b mesylates,5 bromides,6a and amines6b cata-
lyzed by palladium(0) complexes have been carried out
in this manner (eq 1).
One strategy to obtain more functionalized allenic
esters is by using propargylic compounds in which the
leaving group is part of a cyclic structure. In this way,
cyclic alkynyl carbonates can be carbonylated to afford
5-hydroxy-2,3-pentadienoates7 (eq 2). Alkynyl epoxides
fall into this category of compounds. Although these
compounds have been used in C-C coupling reactions
with Pd(0) complexes as catalysts,8 to our knowledge they
have not been reacted with carbon monoxide. In this
paper we report the synthesis of 5-hydroxy-2,3-pentadi-
enoates by carbonylation of epoxyalkynes under mild
conditions. In addition, oxygen heterocycles can be
obtained by carbonylation of hydroxy derivatives of
epoxyalkynes. Depending on the reaction conditions,
dihydrofuranol or their dehydrated products can be
isolated.
Resu lts a n d Discu ssion
X Abstract published in Advance ACS Abstracts, October 1, 1997.
(1) For
a review, see Tsuji, J . Palladium Reagents in Organic
The carbonylation of alkynyl epoxide 1a catalyzed by
tetrakis(methyldiphenylphosphine)palladium afforded
methyl 5-hydroxy-4-methyl-2,3-pentadienoate (2a ) in
70% yield. The allenyl product can be easily identified
by its IR and 13C NMR spectra. The IR spectrum shows
absorption bands at 3417 cm-1 (OH), 1965 cm-1 (CdCdC
stretching), and 1712 cm-1 (CdO). Signals in the 13C
Synthesis; J ohn Wiley and Sons: New York, 1995; pp 453-471.
(2) (a) Elsevier, C. J .; Kleijn, H.; Ruitenberg, K.; Vermeer, P. J .
Chem. Soc., Chem. Commun. 1983, 1529. (b) Elsevier, C. J .; Kleijn,
H.; Boersma, J .; Vermeer, P. Organometallics 1986, 5, 716.
(3) Tsuji, J .; Mandai, T. J . Organomet. Chem. 1993, 451, 15 and
references therein.
(4) (a) Arzoumanian, H.; Choukrad, M.; Nuel, D., J . Mol. Catal.
1993, 85, 287. (b) Murahashi, S. I.; Imada, Y.; Mori, T.; Kitamura, T.
Abstr. J pn. Chem. Soc. Annual Meeting II, 1993, 345.
(5) (a) Marshall, J . A.; Wolf, M. A.; Wallace, E. M., J . Org. Chem.
1997, 62, 367. (b) Marshall, J . A.; Wolf, M. A., J . Org. Chem. 1996,
61, 3238.
(7) Darcel, C.; Buneau, C.; Dixneuf, P. H. Synlett 1996, 218.
(8) (a) Kleojn, H.; Meijer, J .; Overbeek, G. C.; Vermeer, P. Recl. Trav.
Chim. Pays-Bas 1982, 101, 97. (b) Minami, I.; Masami, Y.; Watanabe,
H.; Tsuji, J . J . Organomet. Chem. 1987, 334, 225.
(6) (a) Trieu, N. D.; Elsevier, C. J .; Vrieze, K. J . Organomet. Chem.
1987, 325, C23. (b) Imada, Y.; Alper, H. J . Org. Chem. 1996, 61, 6766.
S0022-3263(97)01303-0 CCC: $14.00 © 1997 American Chemical Society

Carbonylation of Alkynyl Epoxides
J . Org. Chem., Vol. 62, No. 24, 1997 8485
Ta ble 1. Ca r bon yla tion of Alk yn yl Oxir a n es Ca ta lyzed
by (MeP h 2P )4P d a
Sch em e 2
Ta ble 2. Va r ia tion of th e Dia ster eom er ic Ra tio of 1e
Dep en d in g on th e Ca ta lytic System a
ligand
or catalyst
yield (%)
anti/syn
-
0
78
89
88
84
84
90
-
DPPP
97/3
93/7
82/18
97/3
88/12
93/7
DPPB
Ph3Pb
DPPPentane
(Ph3P)4Pdc
c
2
(MePh P)4Pd
a
Reaction conditions: 1a , 0.8 mmol; Pd2(dba)3‚CHCl3, 0.004
b
mmol; ligand, 0.008 mmol; MeOH, 10 mL; 24 h, rt. Using 0.016
mmol of Ph3P. c 0.008 mmol of catalyst and no added ligand.
NMR spectrum appeared at 209.5 ppm for the central
allenyl carbon and at 167 ppm for the carbonyl group.
carbonates,12 where a zwitterionic palladium intermedi-
ate was involved as a key intermediate. In that case,
the driving force of the reaction might be the liberation
of CO2, while in the carbonylation of alkynyl oxiranes the
driving force is the release of ring strain by opening the
epoxide ring (Scheme 2). A noteworthy feature of the
carbonylation of alkynyl oxiranes is that the reaction
conditions are much milder than those for the carbony-
lation of cyclic carbonates.
The effect of different catalytic systems on the carbo-
nylation of 1e is presented in Table 2. Note that not only
is the yield of the reaction affected, but also the diaster-
eomeric ratio of the product. The highest yield is
obtained by using commercially available (MePh2P)4Pd0.
Bidentate phosphine ligands improve the diastereoselec-
tivity. 1,4-Bis(diphenylphosphino)butane (dppb) and 1,5-
bis(diphenylphosphino)pentane both give a 97/3 anti/syn
ratio.
Although we did not determine the configuration of the
major diastereomer, we can assume that the formation
of the anti isomer is favored. Studies on the carbonyla-
tion of chiral mesylates5 and phosphates4b show that the
Pd0 complex reacts with the triple bond in a SN2′ manner.
Any loss in stereoselectivity may be due to a racemization
induced by the same Pd0 catalyst. Nucleophilic attack
of free Pd0Ln at the σ-allenyl-Pd intermediate 3 in anti
After optimization of the reaction conditions, we were
glad to know that the carbonylation reaction takes place
under very mild conditions: 0.8 mmol of the alkynyl
epoxide, 1 mol % of (MePh2P)4Pd, 10 mL of methanol,
300 psi of carbon monoxide, room temperature, 2 h. Two
hours are sufficient to achieve full conversion of the
epoxide, although longer reaction times do not affect the
chemical yields. Methanol is the best solvent for the
reaction. When benzene or THF was used, in the
presence of 0.5 mL of methanol, the conversion was very
low, and the desired allene was not detected in the
reaction mixture, even when the reaction was carried out
at 100 °C. Carbon monoxide pressure above 300 psi does
not improve the product yields. A decrease in the
conversion occurred when the reaction was effected at
less than 200 psi of carbon monoxide.
Table 1 shows the results for the carbonylation of a
series of alkynyl epoxides. Linear substrates (1a -c) give
fine yields of hydroxymethyl allenyl esters. The yields
are quite high for fused bicyclic epoxides (1e-f).
hydroxy derivative of an alkynyl epoxide (1d ) affords a
highly oxygenated allene in lower yield.
The mechanism of the reaction is probably the same
as that proposed for the carbonylation of cyclic alkynyl
A
(9) Baldwin, J . E. J . Chem. Soc., Chem. Commun. 1976, 734.
(10) Baldwin, J . E.; Thomas, R. C.; Kruse, L. I.; Silberman, L. J .
Org. Chem. 1977, 42, 3846.
(11) (a) Cristau, H. J .; Viala, J .; Christol, H., Tetrahedron Lett. 1982,
23, 1569. (b) Stirling, C. J . M. J . Chem. Soc. 1964, 5856 and 5863.
(12) Katsuki, T.; Sharpless, K. B. J . Am. Chem. Soc. 1980, 102, 5976.

8486 J . Org. Chem., Vol. 62, No. 24, 1997
Piotti and Alper
Sch em e 3
Sch em e 5
Sch em e 4
Sch em e 6
We attempted to isolate the diol intermediate by
reacting the protected substrate as a silyl ether (8). The
carbonylation reaction gave 47% yield of the allene 9 (eq
6).
SN2′fashion, followed by allenyl-propargyl rearrange-
ment in the same plane, would give the intermediate 4
(Scheme 3). This racemization could be minimized by
decreasing the amount of catalyst and by using larger
diphosphine ligands.
Ca r bon yla tion of Alk yn yl Oxir a n em eth a n ol
Der iva tives
Following the mechanism proposed above, the carbo-
nylation of alkynyl oxiranemethanol derivative 5a should
lead to the formation of allenyl diol 7 (eq 4).
Deprotection of 9 with Bu4N+F- did not afford the
expected diol, nor the dihydrofuranol derivative 6a .
Instead, the dehydration product of 6a was isolated. The
basicity of F- might induce the dehydration of 6a to form
the more stable aromatic compound 10 in 79% yield
(Scheme 5).
This result suggests that the cyclization of the diol 7
during the carbonylation reaction occurs spontaneously,
following Baldwin’s rules for cyclization reactions.9 For
a trigonal ring closure to be favored, the three reacting
atoms must maintain an angle of R ) 109° during the
reaction pathway. This angle is maintained between
these atoms in the product (Scheme 6).
When the alkynyloxirane 5a is reacted under the
standard conditions, the conversion is complete, but
product 7 was not detected in the reaction mixture.
Instead, the oxygen heterocycle 6a was isolated in 81%
yield (eq 5).
The case of conjugate addition of oxygen nucleophiles
has been studied in some detail.10 The cyclization is
highly favored for 5-exo-trig systems. When the second-
ary hydroxy group in 11 is selectively oxidized, the
hydroxy ketone 12 is not observed, since it cyclizes
spontaneously to 13 (Scheme 7).
This result can be rationalized as a consequence of a
5-exo cyclization of the expected allenyl diol product
under the reaction conditions (Scheme 4). Since the
carbonylation reaction is carried out under neutral
conditions, we can rule out acid or basic catalysis. The
formation of 6a could be due to a Pd-catalyzed cyclization
of the diol or to a noncatalyzed process.
Although compounds containing allenic carboxylic
esters have not been studied, molecular models suggest
that compound 7 can adopt a conformation favorable for
the interaction of the hydroxy group with the π system
of the R,â-unsaturation, making for a very facile cycliza-
tion reaction (Scheme 8).

Carbonylation of Alkynyl Epoxides
J . Org. Chem., Vol. 62, No. 24, 1997 8487
Sch em e 7
Sch em e 9
Sch em e 10
Sch em e 8
In the carbonylation of alkynyl oxiranemethanol de-
rivatives, the dihydrofuranol 17 is formed by a normal
intramolecular Michael type addition (Scheme 10). When
R1 ) Me the product is stable and can be isolated. For
R1 ) H isomerization occurs to give a more stable R,â-
unsaturated ester 18.
Ta ble 3. Ca r bon yla tion of Alk yn yl Oxir a n em eth a n ol
Der iva tivesa
The formation of one or the other isomer is very
selective. The synthesis of the starting epoxides gave
mixtures of diastereomers in the cases of 5d and 5e, and
this ratio is reflected in the cis-trans distribution in the
heterocyclic product (6e: 64/36 cis/trans. 6d : 59/41. We
could not determine which one corresponds to cis or
trans.)
P r ep a r a tion of Ch ir a l Heter ocycles
The transformation of alkynyl oxiranemethanol com-
pounds to 3,4-dihydrofuran-3-ol derivatives proceeds with
loss of stereochemistry at C3 of the starting material.
According to the mechanism of the reaction, the stereo-
chemistry at C1 and C2 should not be affected during the
course of the reaction. The easy synthesis of chiral
alkynyl oxiranemethanol derivatives by Sharpless ep-
oxidation12 makes this carbonylation reaction a potential
route for the preparation of chiral oxygen heterocycles.
The asymmetric epoxidation of 19 to 20 was examined
as a model system (eq 7).
Table 3 shows the results for the carbonylation of a
number of alkynyl oxiranemethanol derivatives. Note
that, depending on the substitution pattern of the start-
ing material, heterocycles containing endo or exo double
bonds are obtained.
Unfortunately, the enantiomeric excess of 20, mea-
sured by chiral GC (Figure 1), was only 47%. The
reaction was repeated two times with the same result.
After one recrystallization of 20 the ee improved to 60%,
and further recrystallizations did not increase the % ee.
A literature search shows that there is only one paper
where the ee of the same compound obtained by Sharp-
less epoxidation is reported.13 In that case, the enantio-
meric excess is 60%, the same value that we obtained.
The preference for the formation of the exo or endo
unsaturated products is likely related to their thermo-
dynamic stability. In fact, the intermolecular addition
of oxygen nucleophiles to allenic compounds containing
an electron acceptor group is well-known.11 The addition
of MeOH to compound 14 gives 15 as the first product.
But depending on the substitution pattern, this com-
pound may isomerize to a more stable conjugated system
16 (Scheme 9).
Carbonylation of 20 gave 21 in 79% yield (eq 8). The
ee was 55%, as determined by the use of an NMR chiral
(13) Pale, P.; Chuche, J . Tetrahedron Lett. 1987, 28, 6447.

8488 J . Org. Chem., Vol. 62, No. 24, 1997
Piotti and Alper
ligand, with larger bidentate ligands favoring the forma-
tion of the anti products.
The carbonylation of alkynyl oxiranemethanol deriva-
tives afford oxygen heterocyclic compounds. These com-
pounds are formed by spontaneous intramolecular Michael
type addition of the diol allenic intermediate, following
Baldwin’s cyclization rules. Depending on the substitu-
tion pattern of the starting epoxide, the heterocycle will
contain an endo or exo carbon-carbon double bond. The
use of enantiomerically enriched alkynyl oxiranemetha-
nol leads to the preparation of an optically active 4,5-
dihydrofuran-3-ol derivative.
Exp er im en ta l Section
Syn th esis of Alk yn yl Oxir a n es 1a -f. The synthesis of
alkynyl oxiranes was carried out by epoxidation of the corre-
sponding enynes.16 These precursors were purchased from
Aldrich or Lancaster and were used as received. The enyne
precursor of 1f was prepared by dehydration of 1-ethynyl-1-
cyclooctanol with POCl3 in pyridine.16
Gen er a l P r oced u r e. To a solution of the enyne (26.2
mmol) in CH2Cl2 (17 mL) at 0 °C was added, in portions, 33
mmol of m-chloroperbenzoic acid. The reaction mixture was
stirred for 15 min at 0 °C, the ice bath was removed, and the
mixture was then stirred for 2 h at room temperature. 10%
Sodium sulfite solution was slowly added until the mixture
gave a negative test with starch-iodide paper. Saturated
sodium bicarbonate solution was added, the aqueous phase
was discarded, and the organic phase was washed twice with
sodium bicarbonate solution, with distilled water (two times),
and finally with brine. The organic phase was dried (magne-
sium sulfate) and filtered, and the solvent was removed using
a rotatory evaporator. The residue was distilled under vacuum,
unless otherwise noted, to yield the desired alkynyl oxirane.
1-Eth yn yl-1-m eth yloxir a n e8a (1a ): 12% yield. The low
yield is probably due to the moderate solubility of 1a in water.
1H NMR (200 MHz) δ ) 1.53 (3H, s), 2.27 (1H, s), 2.72 (1H, d,
J ) 5.6 Hz) and 3.01 (1H, d, J ) 5.6 Hz). 13C NMR: 22.6,
46.8, 55.1, 70.3, 83.1 ppm. IR (neat): 3277, 2119 cm-1. MS:
82 (M+).
F igu r e 1. Determination of enantiomeric excess of 20 and
21 (The racemates are shown on the left side).
shift reagent (Figure 1). Chiral GC could not be used
because 21 dehydrates upon injection into the column.
Ca r bon yla tion of Alk yn yl Oxir a n es 1a -f Ca ta lyzed by
(MeP h 2P )4P d . In a 45 mL stainless steel autoclave equipped
with a magnetic stirring bar, 0.8 mmol of the alkynyl oxirane
was mixed with 10 mL of dry, oxygen-free methanol. To this
solution was added 0.008 mmol of the catalyst. The autoclave
was closed, purged twice with carbon monoxide, and then
pressurized to 300 psi of carbon monoxide. The mixture was
stirred for 2 h at room temperature, the reaction was stopped,
the gas was released, and the solution was filtered through a
short Florisil column (silica gel and aluminum oxide slowly
decompose the allene product). The solvent was removed by
rotatory evaporation. Column chromatography of the crude
mixture was performed by using Florisil as the stationary
phase and hexane/EtOAc 95/5 as the eluant. After 60 mL of
the eluant was used, 80 mL of hexane/EtOAc 60/40 was passed
through the column. Evaporation of this last fraction gave
the desired product.
This result shows that the stereocenter at C2 is
basically unaffected by the reaction, and therefore dif-
ferent chiral oxygen heterocycles derivatives can be
synthesized in this way. It is well-known that com-
pounds of the type 21 can undergo very diastereoselective
hydrogenation14 or epoxidation15 reactions, since the OH
group can act as a directing group. This would allow the
preparation of tetrahydrofuran derivatives containing
three chiral centers, the only chiral source being the
Sharpless epoxidation reaction.
Ca r bon yla tion of 1a Ca ta lyzed by Oth er System s.
General procedure: 0.8 mmol of 1a , 0.004 mmol of Pd2-
(dba)3‚CHCl3, 0.008 mmol of a bidentate phosphine ligand or
0.016 mmol of Ph3P, and 10 mL of methanol were placed in
an autoclave. The autoclave was pressurized to 300 psi of
carbon monoxide, and the mixture was stirred for 24 h. The
reaction was worked up as described before.
Meth yl 5-h ydr oxy-4-m eth yl-2,3-pen tadien oate (2a): 70%
yield. 1H NMR (200 MHz) δ ) 1.78 (3H, d, J ) 2.75 Hz), 3.30
(1H, br), 3.67 (3H, s), 4.08 (2H, d J ) 2.75 Hz), 5.59 (1H, sext,
J ) 2.75 Hz). 13C NMR: 14.4, 52.0, 63.0, 88.4, 105.5, 167.1,
209.5 ppm. IR (neat): 1712, 1965, 3417 cm-1. MS: 142 (M+).
HRMS calcd for C7H10O3: 142.0630. Found: 142.0639.
Con clu sion s
The Pd(0)-catalyzed carbonylation of alkynyl oxiranes
affords 5-hydroxy-2,3-pentadienoates derivatives in good
yields. The reaction may start with a SN2′ attack on the
triple bond by a palladium(0) complex, forming a zwit-
terionic σ-allenylpalladium intermediate, which after
carbon monoxide insertion and attack by methanol leads
to the formation of the product. The diastereomeric ratio
of the product is affected by the nature of the phosphine
(14) Crabtree, R. H.; Davis, M. W. J . Org. Chem. 1986, 51, 2655.
(15) Sharpless, K. B.; Michelson, R. C. J . Am. Chem. Soc. 1973, 95,
6163.
(16) Alexakis, A.; Marek, I.; Mangeney, P.; Normant, J . F. Tetra-
hedron 1991, 47(9), 1667.

Carbonylation of Alkynyl Epoxides
J . Org. Chem., Vol. 62, No. 24, 1997 8489
mathography on Florisil using hexane/EtOAc 95/5 as eluant,
affording 10 in 79% yield.
Sch em e 11
Meth yl 5-h yd r oxy-6-[(ter t-bu tyld im eth ylsilyl)oxy]-4-
m eth yl-2,3-h exa d ien oa te (9): 47% yield. 1H NMR (200
MHz) δ ) 0.06 (3H, s), 0.88 (9H, s), 1.83 (3H, d, J ) 2.6 Hz),
2.70 (1H, br), 3.58 (1H, dd, J ) 10.0 and 6.8 Hz), 3.73 (1H, dd,
J ) 10.0 and 3.9 Hz), 3.70 (3H, s), 4.18 (1H, m), 5.62 (1H, quint,
J ) 2.6 Hz). 13C NMR: -5.2, 14.6, 18.2, 25.8, 51.9, 65.3, 71.7,
88.8, 104.6, 166.5, 209.6 ppm. IR (neat): 3433, 1964, 1715
cm-1. MS: 286 (M+). HRMS calcd for C14H26O4Si: 286.16002.
Found: 286.15683.
Met h yl 3-m et h yl-2-fu r a n a cet a t e20 (10): 1H NMR (200
MHz) δ ) 1.97 (3H, s), 3.60 (2H, s), 3.69 (3H, s), 6.19 (1H, d,
J ) 2.0 Hz), 7.26 (1H, d, J ) 2.0 Hz). 13C NMR: 9.7, 32.0,
52.2, 113.0, 116.9, 141.1, 143.1, 170.1 ppm. IR (neat): 1741
cm-1. MS: 154 (M+).
Syn th esis of (-) 20.12 An oven-dried 500 mL round-bottom
flask was equipped with a magnetic stirring bar, fitted with a
rubber septum, and flushed with nitrogen. The flask was
charged with 400 mL of methylene chloride and 4 g of activated
powdered molecular sieves (4 Å). The flask was cooled to -23
°C using a CCl4/dry ice bath. The following liquids were added
in sequence by syringe while stirring at -23 °C: 11.88 mL
(40 mmol) of titanium isopropoxide, 8.4 mL (40 mmol) of
L-diisopropyltartrate; after stirring during 5 min, 4.16 mL (40
mmol) of trans-3-methylpent-2-en-4-yn-1-ol and 14.6 mL (ca.
80 mmol) of an anhydrous decane solution of TBHP (5-6 M)
were added. The resulting solution was stored overnight in a
freezer at -21 °C. Then the reaction flask was placed in a
CCl4/dry ice bath, and 100 mL of 10% aqueous tartaric acid
solution was added while stirring. The aqueous phase solidi-
fied. The cooling bath was removed after 30 min, and the
mixture was stirred for 2 h. The aqueous phase was separated,
and the organic phase was treated with 10% sodium sulfite
until a negative test with starch/iodide paper was obtained.
The organic phase was washed with water and then with brine
and dried with magnesium sulfate. After filtration and
evaporation of the solvent, the residue was passed through a
short silica gel column using hexane as eluant to separate the
remaining decane. The epoxide was eluted from the column
with ethyl acetate. After evaporation of the solvent, the
product 20 was distilled in a Ku¨gelrohr apparatus and was
collected as a white solid [1.47 gr (40% yield)]. The enantio-
meric excess was 47%. The enantiomeric excess was deter-
mined by capillary chiral GC, using a Lipodex E column,
isothermal run at 90 °C, and 20 psi of the carrier gas (He)
(see Figure 1). A small amount of hexane was added to the
product, and benzene was added dropwise until all the solid
dissolved. The flask was stored in a refrigerator for a few
hours and the solid formed was filtered. The ee of the solid
was 60%. After a second recrystallization, the enantiomeric
excess remained unchanged.
Syn t h esis of Alk yn yl Oxir a n em et h a n ol Der iva t ives
5a -f. The preparation of 5a -f was carried out by epoxidation
of the corresponding alk-2-en-4-yn-1-ol precursors 22 by the
same procedure used for the epoxidation of enynes. With the
exception of the precursor of 5a , which was purchased from
Aldrich, the unsaturated alcohols were prepared following
Scheme 11.18
The cis-trans ratio could be determined by measuring the
coupling constant between R1 and R2 for R1 ) R2 ) H, the
chemical shift of the proton attached to the sp carbon and the
proton chemical shift when R3 ) H.
2-Eth yn yl-2-m eth yloxir a n em eth a n ol13 (5a ): 40% yield.
1H NMR (200 MHz) δ ) 1.60 (3H, s), 2.15 (1H, br), 2.43 (1H,
s,), 3.13 (1H, dd, J ) 6.0 and 4.8 Hz), 3.81 (1H, dd, J ) 13.0
and 5.9 Hz), 3.93 (1H, dd, J ) 13.0 and 4.9 Hz). 13C NMR:
23.0, 51.5, 62.3, 63.7, 73.1, 80.7 ppm. IR (neat): 3214, 2118
cm-1. MS: 112 (M+).
Ca r bon yla tion of Alk yn yl Oxir a n em eth a n ol Der iva -
tives 5a -f. The carbonylation of 5a -f and purification of the
products were carried out using the same procedure as that
described for the carbonylation of alkynyl oxiranes.
Meth yl (4-h yd r oxy-3-m eth yl-4,5-d ih yd r ofu r a n -2-yl)a c-
eta te (6a ): 81% yield. 1H NMR (200 MHz) δ ) 1.72 (3H, s),
3.14 (1H, d, J ) 8 Hz), 3.21 (2H, s), 3.72 (3H, s), 4.18 (1H, dd,
J ) 10.5 and 3.0 Hz), 4.26 (1H, dd, J ) 10.5 and 6.9 Hz), 4.71
(1H, m). 13C NMR: 8.8, 32.0, 52.2, 76.2, 77.4, 109.5, 147.5,
170.0 ppm. IR (neat): 3400, 1727 cm-1. MS: 154 (M+). Anal.
Calcd for C8H1204: C, 55.81; H, 7.02. Found: C, 55.94; H, 6.69.
Met h yl (4-h yd r oxy-5,5-d im et h ylt et r a h yd r ofu r a n -2-
ylid en e)a ceta te (6f): 91% yield. 1H NMR (200 MHz) δ )
1.24 (3H, s), 1.36 (3H, s), 2.92 (1H, d, J ) 4.8 Hz), 3.29 (2H,
m), 3.60 (3H, s), 4.06 (1H, q, J ) 3.7 Hz), 5.22 (1H, t, J ) 1.8
Hz). 13C NMR: 20.7, 25.6, 40.1, 50.8, 74.7, 89.6, 90.0, 169.4,
174.1 ppm. IR (neat): 3436, 1695, 1637 cm-1. MS: 186 (M+).
HRMS calcd for C9H14O4: 186.0892. Found: 186.0872.
Syn th esis a n d Ca r bon yla tion of P r otected Alk yn yl
Oxir a n em eth a n ol 8. The preparation of 8 was carried out
by protection of trans-3-methylpent-2-en-4-yn-1-ol (11) with
tert-butyldimethylsilyl chloride and epoxidation of the silyl
ether.
En a n tiom er ic Excess Deter m in a tion of 21. 21 dehy-
drates upon injection in the GC. Therefore the % ee was
determined by using the NMR chiral shift reagent (+)-Eu(hfc)3,
by examining the splitting of the singlet at 1.72 ppm corre-
sponding to the vinylic methyl group (see Figure 1).
1-(2-Eth yn yl-2-m eth yloxir a n e)eth a n ol, ter t-bu tyld im -
eth ylsilyl eth er 17 (8): 67% yield. 1H NMR (200 MHz) δ )
0.09 (3H, s), 0.89 (9H, s), 1.55 (3H, s), 2.35 (1H, s), 3.01 (1H,
t, J ) 15.0 Hz), 3.78 (1H, dd, J ) 11.2 and 5.0 Hz), 3.89 (1H,
dd, J ) 11.2 and 5.0 Hz). 13C NMR: -5.2, 18.3, 23.0, 25.9,
Ack n ow led gm en t. We are grateful to the Natural
Sciences and Engineering Research Council of Canada
for support of this research.
51.4, 62.9, 64.2, 72.8, 81.2 ppm. IR (neat): 3287, 2123 cm-1
.
MS: 211 (M+ - 15).
Su p p or tin g In for m a tion Ava ila ble: 1H and 13C NMR
spectra of compounds 1b, 2a -f, 5d , 6b-d , and 9. Spectral
data of compunds 1b-f, 2b-f, 5b-f, and 6b-e (30 pages).
This material is contained in libraries on microfiche, im-
mediately follows this article in the microfilm version of the
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Ca r bon yla tion of 8. The carbonylation of 8 and reaction
workup was effected using the same procedure as for 5 to form
9 in 47% yield.
Dep r otection of 9.19 A 250 mg amount of 9 (0.78 mmol)
was dissolved in 5 mL of THF and treated at 0 °C with tetra-
n-butylammonium fluoride (2 equiv) for 5 min. The mixture
was stirred at room temperature for 40 min. The solvent was
evaporated, and the residue was subjected to column chro-
J O971303N
(17) Marshall, J . A.; Du Bay, W. J . J . Org. Chem. 1993, 58, 3435.
(18) Marshall, J . A.; Du Bay, W. J . J . Org. Chem. 1993, 58, 3602.
(19) Yates, P.; Burke, P. M. Can J . Chem. 1987, 65, 1695.
(20) Corey, E. J .; Venkateswarlu, A. J . Am. Chem. Soc. 1972, 94,
6190.