Regio- and enantioselective synthesis of allenic esters by samarium(II)-mediated reduction of propargylic compounds through dynamic kinetic protonation

Article abstract of DOI:10.1016/S0040-4020(00)01044-9

Regioselective synthesis of allenic esters was attained by SmI₂-mediated reduction of propargylic phosphates and ethers bearing alkoxycarbonyl groups at the acetylene terminus. Using suitable chiral proton source in this system, highly enantio-

Full text of DOI:10.1016/S0040-4020(00)01044-9

TETRAHEDRON
Pergamon
Tetrahedron 57 (2001) 889±898
Regio- and enantioselective synthesis of allenic esters by
samarium(II)-mediated reduction of propargylic compounds
through dynamic kinetic protonation
²
Koichi Mikamip and Akihiro Yoshida
Department of Chemical Technology, Tokyo Institute of Technology, Meguro-ku, Tokyo 152-8552, Japan
Dedicated to Professor Jean FrancËois Normant on the occasion of his 65th birthday on January 29th
Received 21 April 2000; accepted 25 September 2000
AbstractÐRegioselective synthesis of allenic esters was attained by SmI2-mediated reduction of propargylic phosphates and ethers bearing
alkoxycarbonyl groups at the acetylene terminus. Using suitable chiral proton source in this system, highly enantio-enriched allenic ester was
obtained through dynamic kinetic resolution by Lewis acidic Sm(III)-mediated enantioselective protonation, even if starting with racemic
propargylic phosphates. q 2001 Elsevier Science Ltd. All rights reserved.
1. Introduction
Allenic esters are valuable synthetic targets, since they
constitute an important class of natural products and the
key intermediates thereof.1 As allenic compounds in the
case that A is not B and X is not Y are chiral, synthesis of
enantio-enriched allenic esters is a challenging subject (Fig.
1). Since van't Hoff predicted the existence of chiral allenic
compounds in 1875,2 much attention has been paid on asym-
metric synthesis of the allenic compounds, particularly
allenic esters. The ®rst asymmetric synthesis of allenic
compounds was reported by Maitland and Mills in 1935.3
They carried out dehydration of racemic allylic alcohol in
Scheme 1.
the presence of optically pure 10-camphorsulfonic acid.
Enantio-enriched allenic compound was obtained via
kinetic resolution of racemic allylic alcohol, though in
quite a low enantiomeric excess (Scheme 1).
Since then, there have been a number of reports on the
asymmetric synthesis of allenes, however, almost all of
them are based on the chirality transfer process starting
from enantio-enriched propargylic compounds. The chiral-
ity transfer reactions include transmission of chirality from
Figure 1.
Keywords: samarium(II) iodide; allenic ester; regioselectivity; enantio-
selectivity; dynamic kinetic resolution; asymmetric protonation.
* Corresponding author. Tel.: 181-3-5734-2142; fax: 181-3-5734-2776;
e-mail: kmikami@o.cc.titech.ac.jp
²
Present address: Faculty of Pharmaceutical Sciences, Teikyo University,
Sagamiko, Kanagawa 199-0195, Japan.
Scheme 2.
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)01044-9

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K. Mikami, A. Yoshida / Tetrahedron 57 (2001) 889±898
ing from propargylic mesylate.6 However, there are a few
reports for enantioselective synthesis of allenes without
chirality transfer.
There are three examples for enantioselective synthesis of
allenic compounds without chirality transfer. Marshall
attempted kinetic resolution of racemic allenylcarbinol by
Sharpless asymmetric epoxidation.7 Naruse reported
destruction of allenedicarboxylate using chiral NMR shift
reagent, Eu(hfc)3 as a chiral Lewis acid.8 Uemura reported
asymmetric oxidation of vinylic selenide followed by
elimination to give an enantio-enriched allenic sulfone.9
This is, however, a chirality transfer reaction of non-racemic
selenium oxide intermediate (Scheme 2).
On the other hand, Professor Inanaga's group and we have
already reported that the reductions of secondary
propargylic phosphates provide allenes with higher regio-
selectivity than the propargylic acetates through samarium-
(II) iodide10-mediated reduction followed by protonation in
the presence of palladium(0) catalyst.11 In contrast, the
reduction of primary propargylic phosphates gave acetylene
derivatives interestingly. Furthermore, we attained the
regiodivergent synthesis of allenes/acetylenes from secon-
dary propargylic phosphates by tuning proton sources12
(Scheme 3).
Scheme 3.
chiral center to allenyl axis. For example, Alexakis and
Normant reported the nucleophilic substitution reaction of
enantio-enriched propargylic acetate by cuprate reagent.4
Marshall reported [2,3] Wittig rearrangement of propargyl
a-stannylalkyl ether via transmetallation from Sn to Li.5
Vermeer reported the cross coupling reaction between
organozinc reagent and allenylpalladium(II) obtained start-
Scheme 4.

K. Mikami, A. Yoshida / Tetrahedron 57 (2001) 889±898
891
Table 1. Regioselective reduction±protonation of propargylic phosphates in the presence of Pd(0) catalyst
aRv ˆ(2R)±CH2CH(CH3)(CH2)2CHvC(CH3)2.
0
bDetermined by 1H NMR analysis.
cSee Ref. 13.
We describe herein samarium(II) iodide-mediated reduction
of secondary and primary propargylic phosphates and ethers
to obtain allenic esters regio- and enantioselectively through
dynamic kinetic protonation without chirality transfer
process.
carbonyl groups at acetylene terminus give acetylenic
compounds regioselectively.11 We have already reported
the regiodivergent synthesis of allenes/acetylenes from
secondary propargylic phosphates as described above.12
Now, we also attained the regiodivergent synthesis of
allenes/acetylenes from primary one by tuning substrates
including alkoxycarbonyl moiety or not. In order to synthe-
size a-allenyl side chain of prostacyclin analogue, this
method is particularly useful because of exclusively high
allene selectivity.13
2. Results and discussion
2.1. Regioselective SmI2-mediated reduction±
protonation
We propose two possible reaction mechanisms. One
contains Umpolung process from s-allenyl/propargyl-
palladium(II) to allenylsamarium(III) species (Scheme 5).
The other involves the reduction of alkoxycarbonyl group
followed by formation of allenylsamarium(III) species
through unstable cumulenic trienolate (Scheme 6).
Finally, kinetic protonation of allenylsamarium(III)
takes place in both mechanisms. It is remarkable that the
latter mechanism includes no palladium(0) catalyst. There-
fore, the reductions without palladium(0) catalyst were
performed (Table 2).
In order to synthesize allenic esters, propargylic compounds
bearing alkoxycarbonyl groups at acetylene terminus were
prepared as follows (Scheme 4).
Samarium(II) iodide-mediated reductions of these
propargylic compounds in the presence of a catalytic
amount
of
tetrakis(triphenylphosphine)palladium(0)
were examined and the results were summarized in
Table 1.
Not only secondary but also primary propargylic substrates
gave allenic esters, and no propiolate derivatives could be
obtained. In contrast, primary substrates without alkoxy-
Propargylic phosphate bearing alkoxycarbonyl group at the
acetylene terminus was reduced to allenic ester as a sole

892
K. Mikami, A. Yoshida / Tetrahedron 57 (2001) 889±898
phosphates. In order to synthesize allenic ester with high
enantiopurity, we attempted chirality transfer reaction
from propargylic phosphate of 91% ee, which was prepared
by asymmetric carbonyl-ene reaction with alkynylogous
analogue of glyoxylate catalyzed by binaphthol±titanium
complex13 followed by phosphorylation.
The chirality transfer reaction was carried out under usual
conditions to give, surprisingly however, essentially
racemic allenic ester (Scheme 7).
The stereochemical course for racemization can be
explained as follows. First, oxidative addition to propargylic
phosphate gives allenylpalladium(II) through back side
attack of palladium(0). Thus, enantio-enriched allenyl-
palladium(II) is stereospeci®cally formed starting from
enantio-enriched propargylic phosphate without loss of
enantiopurity. The cationic allenylpalladium(II) species
are converted to anionic organosamarium(III) species by
double one-electron reductions of samarium(II). This
carbanionic samarium(III) species is readily racemized.
Thus, racemic allenic compound is obtained after proto-
nation with achiral proton source such as tert-butyl alcohol
(Scheme 8).
This result, in turn, suggests the possibility for dynamic
kinetic resolution14 using chiral proton sources15 even
when starting from racemic phosphates, namely deracemi-
zation process of racemic allenylsamarium(III) species (Fig.
2). In addition, organosamarium(III), which is formed by
reduction of phosphates with samarium(II), possesses strong
Lewis acidity and oxophilicity.10 Thus, chiral diols and
hydroxycarbonyl compounds can be effective proton
sources, since the chelation of such chiral alcohols with
samarium(III) can construct a favorable asymmetric
environment.
Scheme 5.
product even without palladium(0) catalyst. Surprisingly,
primary propargyl ether, methoxy group of which possessed
a lower level of the leaving ability, also gave allenic esters.
However, propargylic acetal was not reduced at all and the
starting acetal was recovered. Thus, it is reasonable that the
reactions proceed through latter mechanism as shown in
Scheme 6, when no use of palladium(0) catalyst.
So, we attempted dynamic kinetic resolution by asymmetric
protonation, namely dynamic kinetic protonation, using
racemic propargylic phosphate with various chiral proton
sources (Table 3).16
2.2. Enantioselective SmI2-mediated reduction±
protonation
Next, we attempted the asymmetric synthesis of allenic ester
through chirality transfer reduction of enantio-enriched
First, we examined the C2-symmetrical diols such as
Scheme 6.

K. Mikami, A. Yoshida / Tetrahedron 57 (2001) 889±898
893
Table 2. Regioselective reduction±protonation of propargylic compounds in the absence of Pd(0) catalyst
aDetermined by 1H NMR analysis.
Scheme 7.
Scheme 8.

894
K. Mikami, A. Yoshida / Tetrahedron 57 (2001) 889±898
TADDOL and diisopropyl tartrate, which were often used as
chiral ligands for asymmetric metal complex catalysts
(entries 1±2). The reaction was carried out as follows. To
a THF solution of racemic phosphate was added a chiral
proton source, palladium(0) catalyst, and a THF solution
of samarium(II) iodide at room temperature, and the mixture
was stirred for ten minutes. The enantiomeric excess of the
allenic esters thus obtained was determined by lanthanide
induced shift-NMR (LIS-NMR) method using Eu(hfc)3.17
Medium level of enantioselectivity was observed. The abso-
lute con®guration was determined by Lowe±Brewster's
rule.18 Only when diisopropyl tartrate was used, propiolate
derivative was also obtained as a by-product (entry 2).12
Next, we used a-hydroxycarbonyl compounds and 1,2-
diols, which could form 5-membered chelate because of
high Lewis acidity of trivalent samarium (entries 3±6).
All chiral proton sources gave enantio-enriched allenic
ester and no propiolate derivative was obtained. In
Figure 2.
Table 3. Regio- and enantioselective reduction±protonation of propargylic phosphate
a
Determined by LIS-NMR analysis using Eu(hfc)3.
Determined by Lowe±Brewster's rule.
Acetylene-type product was also obtained in 9% yield.
b
c

K. Mikami, A. Yoshida / Tetrahedron 57 (2001) 889±898
895
chromatography were performed with a Shimadzu LC-6A
instrument equipped with a Shimadzu SPD-6A spectro-
meter as an ultra violet (UV) light detector. Peak area was
calculated by a Shimadzu C-R6A as an automatic integrator.
Tetrahydrofuran was distilled from sodium benzophenone
ketyl immediately prior to use. Dichloromethane was
freshly distilled from calcium hydride.
Figure 3.
3.2. Preparation of propargylic phosphates
particular, hydrobenzoin gave allenic ester with high
chemical and high optical yield (entry 5).
3.2.1. Methyl (^)-5-(cyclohex-1-en-1-yl)-4-hydroxypent-
2-ynoate. To a solution of methyl 3-formylpropiolate
(102 mg, 0.91 mmol) in dry dichloromethane (3 mL) were
added methylidenecyclohexane (0.13 mL, 1.1 mmol) and
then a 1.0 M solution of tin(IV) chloride in dichloromethane
(0.91 mL, 0.91 mmol) at 2788C under an argon atmos-
phere. After stirring for 3 h, the reaction mixture was poured
into a saturated aqueous solution of sodium hydrogen-
carbonate, ®ltered through a pad of Celite and extracted
three times with ethyl acetate. The combined organic
layer was washed with brine, dried over anhydrous mag-
nesium sulfate and evaporated under reduced pressure.
Puri®cation by silica-gel column chromatography (hexane/
ethyl acetateˆ4:1) afforded methyl 5-(cyclohex-1-en-1-yl)-
Finally, we employed the cyclic chiral proton sources,
which could form bicyclo[3.3.0]octane system such as
pyrrolidinemethanols and pantolactone in order to construct
a more rigid transition state (entries 7±9). As we would have
expected, enantio-enriched allenic ester was obtained with
exclusively high regioselectivity. In particular, pantolactone
gave allenic ester in much more than 50% yield, the
maximum yield through ordinary kinetic resolution, with
extremely high enantiomeric excess (entry 9).
The sense of asymmetric protonation to provide (R)-allenic
ester using (R,R)-hydrobenzoin (or pantolactone) correlates
well to this transition state model, wherein the severe steric
repulsion between alkyl groups is operative in the right
diastereomer. Thus, protonation proceeds through the favor-
able diastereomer in left-hand side to give highly enantio-
enriched allenic ester (Fig. 3).
1
4-hydroxypent-2-ynoate in 85% yield (162 mg). H NMR
(300 MHz, CDCl3) d 1.5±1.7 (m, 4H), 1.9±2.1 (m, 5H),
2.41 (d, Jˆ6.8 Hz, 2H), 3.77 (s, 3H), 4.55 (t, Jˆ6.8 Hz,
1H), 5.61 (br.s, 1H). 13C NMR (75 MHz, CDCl3) d 22.0,
22.6, 25.2, 28.3, 43.4, 52.7, 60.1, 76.1, 88.1, 127.0, 132.3,
153.9. IR (neat)3436, 2932, 2862, 2240, 1717, 1644, 1437,
1377, 1257, 1199, 1178, 1104, 1050, 915, 859, 803,
In summary, we report here ef®cient regiospeci®c synthesis
of allenic esters and the ®rst example of the asymmetric
synthesis of allenic compounds through dynamic kinetic
protonation of anionic allenylsamarium(III) species without
involvement of chirality transfer or destruction of one
enantiomer. The present protonation using chiral proton
sources such as hydrobenzoin and pantolactone will provide
a powerful strategy using racemic allenyl carbanion species
for the asymmetric synthesis of allenic compounds.
This ef®cient asymmetric protonation could be attained
due to the chelation of chiral alcohol with samarium(III)
possessing strong Lewis acidity and oxophilicity. Thus,
we now investigate the development of asymmetric reac-
tions promoted by samarium(III) species obtained after the
reduction of various organic compounds with samarium(II).
733 cm21
.
3.2.2. Methyl (R)-(1)-5-(cyclohex-1-en-1-yl)-4-hydroxy-
pent-2-ynoate. To a suspension of powdered molecular
sieves 4A (MS 4A; 100 mg) in dry dichloromethane
(3 mL) were added (R)-binaphthol±titanium dichloride
catalyst (50 mg, 0.125 mmol, 10 mol%), methylidenecyclo-
hexane (0.18 mL, 1.5 mmol) and then freshly-distilled
methyl 3-formylpropiolate (140 mg, 1.25 mmol) at 08C
under an argon atmosphere. After stirring overnight at that
temperature, the reaction mixture was diluted with diethyl
ether and poured into a saturated aqueous solution of
sodium hydrogencarbonate. MS 4A was ®ltered off through
a pad of Celite and the ®ltrate was extracted twice with
diethyl ether and once with ethyl acetate. The combined
organic layer was washed with brine, dried over anhydrous
magnesium sulfate and evaporated under reduced pressure.
Puri®cation by silica-gel column chromatography (hexane/
ethyl acetateˆ4:1) afforded methyl (R)-(1)-5-(cyclohex-1-
en-1-yl)-4-hydroxypent-2-ynoate in 95% yield (248 mg).
3. Experimental
3.1. General
1
Boiling points were uncorrected. H and 13C NMR spectra
26
[a]D ˆ146.68 -(c 1.20, CHCl3), 91% ee. HPLC (DAICEL
were measured on a Varian GEMINI 300 (300 MHz), a
JEOL GSX-500 (500 MHz) and a JEOL EX-270 (270
MHz) spectrometers. Chemical shifts of H NMR were
CHIRALCEL OD, eluent, hexane/2-propanolˆ20:1, ¯ow
rate 0.6 mL/min, detection 230-nm light) tR of (R)-isomer
15.2 min and (S)-isomer 17.4 min. 1H NMR, 13C NMR, IR:
See corresponding racemic product.
1
expressed in parts per million relative to chloroform (d
7.26) or tetramethylsilane (d 0.00) as an internal standard
in chloroform-d. Chemical shifts of 13C NMR were
expressed in parts per million relative to chloroform-d (d
77.0) as an internal standard. IR spectra were measured on a
JASCO FT/IR-5000 spectrometer. Optical rotations were
measured on a JASCO DIP-140. High-performance liquid
3.2.3. Methyl (R)-(1)-5-(cyclohex-1-en-1-yl)-4-[(diethoxy-
phosphoryl)oxy]pent-2-ynoate. To a solution of methyl (R)-
(1)-5-(cyclohex-1-en-1-yl)-4-hydroxypent-2-ynoate (48 mg,
0.23 mmol) in dry tetrahydrofuran (4 mL) was added a
1.6 M solution of butyllithium in hexane (0.14 mL,

896
K. Mikami, A. Yoshida / Tetrahedron 57 (2001) 889±898
0.23 mmol) at 2788C under a nitrogen atmosphere. After
stirring for 1 h, to the resultant solution was added triethyl-
amine (0.038 mL, 0.28 mmol) and then diethyl chlorophos-
phate (0.040 mL, 0.28 mmol), then the mixture was warmed
to 08C. After stirring for 1 h at that temperature, the reaction
mixture was poured into a saturated aqueous solution of
ammonium chloride and extracted three times with ethyl
acetate. The combined organic layer was washed with
brine, dried over anhydrous magnesium sulfate and evapo-
rated under reduced pressure. Puri®cation by silica-gel
column chromatography (hexane/ethyl acetateˆ3:1)
afforded methyl (R)-(1)-5-(cyclohex-1-en-1-yl)-4-[(diethoxy-
sodium hydrogencarbonate, and extracted three times with
dichloromethane. The combined organic layer was washed
with brine, dried over anhydrous sodium sulfate and
distilled under reduced pressure to afford pure 2-[(prop-2-
yn-1-yl)oxy]tetrahydropyran in 95% yield (2.001 g). bp 63±
1
658C/9 mmHg. H NMR (300 MHz, CDCl3) d 1.4±1.9 (m,
6H), 2.41 (t, Jˆ2.4 Hz, 1H), 3.5±3.6 (m, 1H), 3.8±3.9 (m,
1H), 4.24 (dd, Jˆ2.4, 15.7 Hz, 1H), 4.28 (dd, Jˆ2.4,
15.7 Hz, 1H), 4.82 (t, Jˆ3.3 Hz, 1H). 13C NMR (75 MHz,
CDCl3) d 18.9, 25.2, 30.1, 54.0, 62.0, 73.9, 76.6, 96.9.
3.2.6. Octyl 4-[(tetrahydropyran-2-yl)oxy]but-2-ynoate.
To a solution of 2-[(prop-2-yn-1-yl)oxy]tetrahydropyran
(0.84 mL, 6.0 mmol) in dry tetrahydrofuran (6 mL) was
added a 1.6 M solution of butyllithium in hexane (4.1 mL,
6.6 mmol) at 2788C under a nitrogen atmosphere. After
stirring for 1 h at that temperature, octyl chloroformate
(1.3 mL, 6.6 mmol) was added to the resultant solution.
After stirring for 2 h at that temperature, the reaction
mixture was poured into a saturated aqueous solution of
ammonium chloride and extracted three times with ethyl
acetate. The combined organic layer was washed with
brine, dried over anhydrous sodium sulfate and evaporated
under reduced pressure to afford octyl 4-[(tetrahydropyran-
2-yl)oxy]but-2-ynoate (2.083 g), the crude product, which
would be used in the next step without further puri®cation.
1H NMR (300 MHz, CDCl3) d 0.88 (t, Jˆ6.9 Hz, 3H), 1.2±
1.4 (m, 10H), 1.5±1.9 (m, 8H), 3.5±3.6 (m, 1H), 3.8±3.9
(m, 1H), 4.17 (t, Jˆ6.7 Hz, 2H), 4.38 (s, 2H), 4.81 (t, Jˆ
3.1 Hz, 1H). 13C NMR (75 MHz, CDCl3) d 14.2, 18.9, 22.7,
25.3, 25.9, 28.4, 29.2, 29.2, 30.1, 31.8, 53.7, 62.0, 66.3,
77.6, 83.4, 97.1, 153.2. IR (neat) 2932, 2860, 2242, 1717,
1458, 1390, 1346, 1251, 1203, 1125, 1029, 944, 903, 872,
1
phosphoryl)oxy]pent-2-ynoate in 94% yield (75 mg). H
NMR (300 MHz, CDCl3) d 1.33 (dq, Jˆ1.1, 7.0 Hz, 6H),
1.5±1.7 (m, 4H), 1.8±2.1 (m, 4H), 2.44 (dd, Jˆ6.2, 13.9 Hz,
1H), 2.53 (dd, Jˆ7.8, 13.9 Hz, 1H), 3.77 (s, 3H), 4.0±4.2
(m, 4H), 5.13 (dt, Jˆ6.2, 7.8 Hz, 1H), 5.59 (br.s, 1H). 13C
3
NMR (75 MHz, CDCl3) d 15.9 (d, JCCOPˆ5.3 Hz), 21.9,
3
22.6, 25.2, 28.1, 44.2 (d, JCCOPˆ6.3 Hz), 52.8, 64.1 (d,
2
2
2JCOPˆ5.9 Hz), 64.3 (d, JCOPˆ5.9 Hz), 65.7 (d, JCOP
ˆ
3
5.9 Hz), 77.7, 84.4 (d, JCCOPˆ3.0 Hz), 126.9, 131.2,
153.5. IR (neat) 3430, 3248, 2988, 2934, 2862, 2246,
.
1721, 1437, 1373, 1251, 1168, 980, 806, 750 cm21
26
[a]D ˆ34.78 (c 1.50, CHCl3), 91% ee.
3.2.4. Methyl 4-[(diethoxyphosphoryl)oxy]undec-2-ynoate.
To a solution of methyl propiolate (0.44 mL, 5.0 mmol) in
dry tetrahydrofuran (8 mL) was added a 1.0 M solution of
lithium hexamethyldisilazide in tetrahydrofuran (5.0 mL,
5.0 mmol) dropwise at 2788C under a nitrogen atmosphere.
After stirring for 15 min at that temperature, octanal
(0.86 mL, 5.5 mmol) was added to the resultant solution,
then the mixture was stirred for 1 h at that temperature,
and for 1 h at 08C. After adding diethyl chlorophosphate
(2.60 mL, 18 mmol) to the reaction mixture, the mixture
was stirred for 1 h at that temperature. The resultant mixture
was poured into a saturated aqueous solution of ammonium
chloride and extracted three times with ethyl acetate. The
combined organic layer was washed with brine, dried over
anhydrous magnesium sulfate and evaporated under
reduced pressure. Puri®cation by silica-gel column chroma-
tography (hexane/ethyl acetateˆ2:1) afforded methyl
4-[(diethoxyphosphoryl)oxy]undec-2-ynoate in 71% yield
(1.241 g). 1H NMR (300 MHz, CDCl3) d 0.84 (t, Jˆ
6.9 Hz, 3H), 1.2±1.3 (m, 8H), 1.31 (dq, Jˆ1.1, 7.1 Hz,
3H), 1.33 (dq, Jˆ1.1, 7.1 Hz, 3H), 1.4±1.5 (m, 2H), 1.8±
1.9 (m, 2H), 3.75 (s, 3H), 4.0±4.2 (m, 4H), 5.03 (q, Jˆ
6.9 Hz, 1H). 13C NMR (75 MHz, CDCl3) d 13.9, 15.9 (d,
3JCCOPˆ7.3 Hz), 22.5, 24.4, 28.8, 28.9, 31.6, 35.6 (d,
750 cm21
.
3.2.7. Octyl 4-hydroxybut-2-ynoate. To a solution of octyl
4-[(tetrahydropyran-2-yl)oxy]but-2-ynoate (2.083 g), the
crude material obtained as above, in tetrahydrofuran
(10 mL) and water (2 mL) was added p-toluenesulfonic
acid monohydrate (456 mg, 2.4 mmol) at room temperature.
After stirring for 1 day at that temperature, the reaction
mixture was poured into a saturated aqueous solution of
sodium hydrogencarbonate and extracted three times with
diethyl ether. The combined organic layer was washed with
a saturated aqueous solution of sodium hydrogencarbonate
and brine, dried over anhydrous sodium sulfate and evapo-
rated under reduced pressure. Puri®cation by silica-gel
column chromatography (hexane/ethyl acetateˆ8:1)
afforded octyl 4-hydroxybut-2-ynoate in 87% yield
2
1
3JCCOPˆ6.1 Hz), 52.7, 64.0 (d, JCOPˆ7.3 Hz), 64.1 (d,
(2 steps, 1.022 g). H NMR (300 MHz, CDCl3) d 0.87 (t,
2
2JCOPˆ6.1 Hz), 67.0 (d, JCOPˆ6.1 Hz), 77.4, 84.2 (d,
Jˆ6.9 Hz, 3H), 1.2±1.4 (m, 10H), 1.6±1.7 (m, 2H), 2.21 (t,
Jˆ6.3 Hz, 1H), 4.17 (t, Jˆ6.7 Hz, 2H), 4.39 (d, Jˆ6.3 Hz,
2H). 13C NMR (75 MHz, CDCl3) d 13.9, 22.5, 25.6, 28.2,
29.0, 29.0, 31.6, 50.6, 66.4, 77.3, 85.1, 153.6. IR (neat)
3420, 2932, 2860, 2242, 1715, 1444, 1386, 1253, 1079,
3JCCOPˆ4.8 Hz), 153.3. IR (neat) 2958, 2932, 2862, 2246,
1723, 1636, 1437, 1371, 1261, 1166, 1033, 750 cm21
.
3.2.5. 2-[(Prop-2-yn-1-yl)oxy]tetrahydropyran. Octyl
4-[(diethoxyphosphoryl)oxy]but-2-ynoate was prepared
from prop-2-yn-1-ol described as follows. To a solution of
prop-2-yn-1-ol (propargyl alcohol; 0.87 mL, 18 mmol) in
dry dichloromethane (15 mL) were added 2H-3,4-dihydro-
pyran (1.37 mL, 15 mmol) and then pyridinium p-toluene-
sulfonate (377 mg, 1.5 mmol) at room temperature under a
nitrogen atmosphere. After stirring for 15 h, the reaction
mixture was poured into a saturated aqueous solution of
1025, 752 cm21
.
3.2.8. Octyl 4-[(diethoxyphosphoryl)oxy]but-2-ynoate. To
a solution of octyl 4-hydroxybut-2-ynoate (738 mg, 3.76
mmol) in dry tetrahydrofuran (4 mL) was added a 1.56 M
solution of butyllithium in hexane (2.4 mL, 3.76 mmol) at
2788C under a nitrogen atmosphere. After stirring for
30 min at that temperature, diethyl chlorophosphate

K. Mikami, A. Yoshida / Tetrahedron 57 (2001) 889±898
897
(0.65 mL, 4.50 mmol) was added to the resultant solution,
then the mixture was warmed to 08C. After stirring for 2 h
at that temperature, the reaction mixture was poured into a
saturated aqueous solution of ammonium chloride and
extracted three times with ethyl acetate. The combined
organic layer was washed with brine, dried over anhydrous
sodium sulfate, and evaporated under reduced pressure. Puri-
®cation by silica-gel column chromatography (hexane/ethyl
acetateˆ3:1) afforded octyl 4-[(diethoxyphosphoryl)oxy]but-
2-ynoate in 42% yield (552 mg). 1H NMR (300 MHz,
CDCl3) d 0.87 (t, Jˆ7.0 Hz, 3H), 1.2±1.4 (m, 10H), 1.33
(dt, Jˆ1.1, 7.1 Hz, 3H), 1.35 (dt, Jˆ1.1, 7.1 Hz, 3H), 1.6±
1.7 (m, 2H), 4.0±4.2 (m, 2H), 4.77 (d, Jˆ10.4 Hz, 2H). 13C
25.6, 28.2, 29.0, 29.0, 31.6, 61.5, 66.4, 76.2, 81.0, 90.9,
153.4.
3.4. Typical procedure for palladium(0)-catalyzed
reduction of propargylic compounds with samarium(II)
iodide
3.4.1. Methyl (R)-(2)-5-(cyclohex-1-en-1-yl)penta-2,3-
dienoate. To a solution of methyl (R)-(1)-5-(cyclohex-1-
en-1-yl)-4-[(diethoxyphosphoryl)oxy]pent-2-ynoate (75 mg,
0.22 mmol), tetrakis(triphenylphosphine)palladium(0) (13
mg, 0.011 mmol; 5 mol%) and (R)-styrene glycol (33 mg,
0.24 mmol; as a proton source) in dry tetrahydrofuran
(2 mL) was added a 0.1 M solution of samarium(II) iodide
in tetrahydrofuran (5.5 mL, 0.55 mmol) at room tempera-
ture under an argon atmosphere. After stirring for 10 min,
the reaction mixture was poured into a saturated aqueous
solution of ammonium chloride, ®ltered through pads of
Celite±Florisil and extracted three times with diethyl
ether. The combined organic layer was washed with brine,
dried over anhydrous sodium sulfate and evaporated under
reduced pressure. Puri®cation by silica-gel column chroma-
tography (pentane) afforded methyl (R)-(2)-5-(cyclohex-1-
en-1-yl)penta-2,3-dienoate. in 86% yield (36 mg). The
regioselectivity was .99% allene, determined by 1H
3
NMR (75 MHz, CDCl3) d 13.9, 15.9 (d, JCCOPˆ6.7 Hz),
3
16.0 (d, JCCOPˆ7.1 Hz), 22.5, 25.6, 28.2, 29.0, 29.0, 31.6,
2
2
54.3 (d, JCOPˆ4.7 Hz), 64.3 (d, JCOPˆ5.8 Hz), 66.4, 78.8,
80.6 (d, 3JCCOPˆ7.4 Hz), 153.0. IR (neat) 2924, 2862, 2250,
1717, 1460, 1394, 1373, 1251, 1168, 1029, 832, 750 cm21.
3.3. Preparation of propargylic ether and acetal
3.3.1. Octyl 4-methoxybut-2-ynoate. To a solution of
methyl prop-2-yn-1-yl ether (0.46 mL, 5.5 mmol) in dry
tetrahydrofuran (5 mL) was added a 1.65 M solution of
butyllithium in hexane (3.33 mL, 5.5 mmol) dropwise at
2788C under a nitrogen atmosphere. After stirring for 1 h
at that temperature, octyl chloroformate (0.98 mL,
5.0 mmol) was added to the reaction mixture. After stirring
for 2.5 h at that temperature, the resultant mixture was
poured into a saturated aqueous solution of ammonium
chloride and extracted three times with ethyl acetate. The
combined organic layer was washed with brine, dried over
anhydrous magnesium sulfate and evaporated under
reduced pressure. Puri®cation by silica-gel column chroma-
tography (hexane/ethyl acetateˆ15:1) afforded octyl
1
NMR analysis. H NMR (300 MHz, CDCl3) d 1.5±1.7 (m,
4H), 1.9±2.1 (m, 4H), 2.6±2.9 (m, 2H), 3.73 (s, 3H), 5.4±
5.7 (m, 3H). 13C NMR (75 MHz, CDCl3) d 22.2, 22.9, 25.1,
28.0, 36.2, 51.9, 87.6, 93.8, 123.2, 135.1, 166.8, 213.0. IR
(neat) 2928, 1961, 1723, 1439, 1408, 1375, 1261, 1195,
1162, 1035, 803 cm21. [a]D ˆ20.418 (c 0.90, CHCl3),
25
13% ee.
1
3.4.2. Methyl undeca-2,3-dienoate. H NMR (300 MHz,
CDCl3) d 0.87 (t, Jˆ6.9 Hz, 3H), 1.2±1.4 (m, 8H), 1.4±
1.5 (m, 2H), 2.12 (dq, Jˆ3.3, 6.9 Hz, 2H), 3.73 (s, 3H),
5.58 (dt, Jˆ3.3, 6.9 Hz, 1H), 5.60 (q, Jˆ6.9 Hz, 1H). 13C
NMR (75 MHz, CDCl3) d 14.1, 22.7, 27.6, 28.8, 29.0, 29.1,
31.9, 52.0, 88.0, 95.5, 166.8, 212.5. IR (neat) 2930, 2862,
1963, 1725, 1663, 1537, 1439, 1412, 1346, 1325, 1259,
1
4-methoxybut-2-ynoate in 89% yield (1.002 g). H NMR
(300 MHz, CDCl3) d 0.88 (t, Jˆ6.6 Hz, 3H), 1.2±1.4 (m,
10H), 1.6±1.7 (m, 2H), 3.41 (s, 3H), 4.17 (t, Jˆ6.8 Hz, 2H),
4.22 (s, 2H). 13C NMR (75 MHz, CDCl3) d 13.9, 22.5, 25.7,
28.3, 29.0, 29.0, 31.6, 58.0, 59.4, 66.3, 78.3, 83.0, 153.4. IR
(neat) 2930, 2862, 2238, 1781, 1717, 1466, 1379, 1359,
1230, 1195, 1162, 1035, 872, 801 cm21
.
1249, 1189, 1162, 1110, 1065, 944, 909, 750 cm21
.
3.4.3. Octyl allenecarboxylate. 1H NMR (300 MHz,
CDCl3) d 0.87 (t, Jˆ6.9 Hz, 3H), 1.2±1.4 (m, 10H),
1.64 (tt, Jˆ6.8, 7.4 Hz, 2H), 4.12 (t, Jˆ6.8 Hz, 2H), 5.20
(d, Jˆ6.5 Hz, 2H), 5.63 (t, Jˆ6.5 Hz, 1H). 13C NMR
(75 MHz, CDCl3) d 13.9, 22.5, 25.7, 28.5, 29.1, 29.1,
31.7, 65.1, 79.2, 88.1, 166.0, 216.0. IR (neat) 2930, 2860,
1974, 1943, 1719, 1468, 1427, 1383, 1342, 1299, 1261,
3.3.2. Octyl 4,4-diethoxybut-2-ynoate. To a solution of
propiolaldehyde diethyl acetal (0.79 mL, 5.5 mmol) in dry
tetrahydrofuran (5 mL) was added a 1.58 M solution of
butyllithium in hexane (3.50 mL, 5.5 mmol) dropwise at
2788C under a nitrogen atmosphere. After stirring for 1 h
at that temperature, octyl chloroformate (0.70 mL,
3.6 mmol) was added to the reaction mixture. After stirring
for 2.5 h at that temperature, the resultant mixture was
poured into a saturated aqueous solution of ammonium
chloride and extracted three times with ethyl acetate. The
combined organic layer was washed with brine, dried over
anhydrous sodium sulfate and evaporated under reduced
pressure. Puri®cation by silica-gel column chromatography
(hexane/ethyl acetateˆ20:1) afforded octyl 4,4-diethoxy-
1166, 1085, 1021, 859 cm21
.
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1
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