Palladium-catalyzed cyclization reactions of propargylic carbonates with nucleophiles: A methodology for the syntheses of substituted 2,3-dihydrofurans and benzofurans

Article abstract of DOI:10.1016/j.tet.2005.02.077

Phenoxy-substituted 2,3-dihydrofurans were synthesized by the palladium-catalyzed reaction of 5-methoxycarbonyloxy-3-pentyn-1-ol with phenols. The propargylic carbonate containing a nucleophilic phenoxy group also reacted in the presence of palladium to p

Full text of DOI:10.1016/j.tet.2005.02.077

Tetrahedron 61 (2005) 4381–4393
Palladium-catalyzed cyclization reactions of propargylic
carbonates with nucleophiles: a methodology for the syntheses of
substituted 2,3-dihydrofurans and benzofurans
*
Masahiro Yoshida, Yukio Morishita, Mika Fujita and Masataka Ihara
*
Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Aobayama, Sendai 980-8578, Japan
Received 8 February 2005; revised 28 February 2005; accepted 28 February 2005
Available online 18 March 2005
Abstract—Phenoxy-substituted 2,3-dihydrofurans were synthesized by the palladium-catalyzed reaction of 5-methoxycarbonyloxy-3-
pentyn-1-ol with phenols. The propargylic carbonate containing a nucleophilic phenoxy group also reacted in the presence of palladium to
produce the product. The reaction of 1-(2-hydroxyphenyl)-3-methoxycarbonyloxy-1-propyne with 2-methyl-1,3-cyclohexanedione or
2-methyl-1,3-cycohexanedione yielded the substituted benzofurans. The propargylic compound having a acetoxy group as a leaving group
exhibited similar reactivity.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
the initially formed p-propargylpalladium species are
subjected to the nucleophilic attack of phenols leading to
the p-allylpalladium intermediate, and then cyclization via
the fixation of the resulting CO2 produces the phenoxy-
substituted cyclic carbonates. To examine the scope of the
reactivity of hydroxyl-substituted propargylic compounds
with nucleophiles, we have focused on the propargylic
The reactions of propargylic compounds with palladium
catalysts have received much attention due to their versatile
and specific reactivity, and extensive studies of these have
now been attempted.1 Palladium-catalyzed reaction of
propargylic carbonates with nucleophiles is one of the
most successful chemical processes that have been
developed.2,3 The reaction can be normally carried out
under neutral conditions, and a number of various complex
molecules can be prepared by specific substrate design.
Based upon our knowledge of these reactions, we have
recently developed the cascade reaction of propargylic
carbonates, containing a hydroxyl group at the propargylic
position, with phenols (Scheme 1).4 During the reactions,
Scheme 1.
Keywords: Palladium; Cyclization; Dihydrofurans; Phenols.
*
Corresponding authors. Fax: C81 22 2176877;
e-mail: mihara@mail.pharm.tohoku.ac.jp
Scheme 2.
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.02.077

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compound 1 which has a hydroxyl group at the homo-
propargylic position (Scheme 2). When the substrate 1 is
subjected to the reaction with nucleophile in the presence
of palladium catalyst, the corresponding p-propargyl-
palladium complex 3 would be initially formed. There
would be two possible pathways from 3, one is the
intermolecular attack of a nucleophile leading to 5, and
the other is the intramolecular attack of the resulting
hydroxy ion to give cyclized intermediate 4. Herein, we
describe a palladium-catalyzed reaction of propargylic
carbonates, possessing a homopropargylic hydroxyl group,
with nucleophiles.5
having a p-methoxybenzyloxy (MPM) group was subjected
to the Corey–Fuchs reaction to afford the propargylic
alcohol 7a. Reaction of 7a with methyl chloroformate
followed by deprotection of MPM group in the presence of
2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and
H2O gave a propargylic carbonate 1a. To synthesize
substrates containing a substituent at the propargylic
position, oxidation of 7a and the subsequent addition of
methyl lithium yielded a methyl-substituted propargylic
alcohol 7b. According to the same procedure for 1a, 7b was
converted to the methyl-substituted propargylic carbonate
1b in 2 steps. Similarly, the substrates 1c and 1d having a
pentyl and a phenyl group were obtained, respectively, from
7a. The substrate 1e, which has no substituent at the
propargylic position, was also synthesized from 7e. For the
preparation of the substrate 1f having a cyclohexane ring,
cyclohexene oxide 9 was subjected to the reaction with
tetrahydro-2-(2-propynyloxy)-2H-pyran followed by
2. Results and discussion
The substrates 1a–g for the palladium-catalyzed reactions
were synthesized as follows (Scheme 3). The aldehyde 6
Scheme 3.

M. Yoshida et al. / Tetrahedron 61 (2005) 4381–4393
4383
deprotection of THP group to afford diol 10. The diol 10 was
selectively transformed to the propargylic carbonate 1f. To
test the internal reaction, p-methoxyphenyl (PMP) carbon-
ate 1g was synthesized from 7a with PMP chloroformate.
Our initial attempt at the palladium-catalyzed reactions
began with 1a and p-methoxyphenol (2a) (Table 1). When
1a was subjected to the reaction with 2a in the presence of
5 mol% Pd2(dba)3$CHCl3 and 20 mol% 1,2-bis(diphenyl-
phosphino)ethane (dppe) in dioxane at 60 8C, the dihydro-
furan 11aa having a p-methoxyphenoxy group was
produced in 45% yield (entry 1). Although the similar
reactivity was observed in the presence of 1,3-bis(di-
phenylphosphino)propane (dppp) (entry 2), the yields have
were increased when 1,4-bis(diphenylphosphino)butane
(dppb) and 1,10-bis(diphenylphosphino)ferrocene (dppf)
were used as a ligand, respectively (entries 3 and 4). On
the other hand, it was made clear that monodentate ligands
P(o-Tol)3 and PPh3 were less effective for the reactions
(entries 5 and 6).
Table 1. Optimization studies in the palladium-catalyzed reaction of 1a
with p-methoxyphenol (2a)
Scheme 5.
hindered site produces dihydrofuran 11.8 As another
possible pathway, the initial reaction of the phenoxide
with the p-propargyl complex 3 followed by the cyclization
of the resulting p-allyl complex 5 could yield dihydropyran
14,9 but no formation of 14 was observed.
Entry
Ligand
Yield (%)a
1
2
3
4
dppe
dppp
dppb
dppf
P(o-Tol)3
PPh3
45 (61)
40 (45)
74
84
N.R.
To examine the scope of this reaction, various substituted
phenols were used as the nucleophiles (Table 2). The
corresponding dihydrofurans 11ab–11ad formed in high
yields when phenols bearing an electron donating group
2b–2d reacted with propargylic carbonate 1a (entries 1–3).
Reactions of phenol (2e) and 1-naphthol (2f) also produced
the corresponding products 11ae and 11af in good yields
(entries 4 and 5). Dihydrofurans 11ag–11ai were obtained in
acceptable yields by the reactions employing an electron
withdrawing group substituted phenols 2g–2i (entries 6–8).
5
6b
15 (28)
PMPZp-methoxyphenyl.
a The yields in parentheses are based on recovered starting material.
b 10 mol% Pd(PPh3)4 was used as a palladium catalyst.
The structure of the resulting product 11aa was determined
by the transformation to the known compound 126
(Scheme 4). Thus, catalytic hydrogenation of 11aa,
followed by the removal of a p-methoxyphenyl group with
CAN produced compound 12.
Table 2. Reactions of propargylic carbonate 1a with various phenols 2b–2i
Scheme 4.
Entry
ArOH
Product
Yield (%)a
A plausible mechanism for the formation of the dihydro-
furan 11 is shown in Scheme 5. In this process, the
palladium catalyst initially promotes decarboxylation of a
propargylic carbonate 1 to generate the allenylpalladium
complex 13. Species 13 is regarded as the p-propargylpal-
ladium complex 3,7 which undergoes intramolecular
nucleophilic attack7d by the resulting internal hydroxide to
produce the p-allylpalladium intermediate 4. Finally,
regioselective addition of phenoxide to 4 at the less
1
2
3
4
5
6
7
8
2b: RZ2-OMe
2c: RZ4-Me
2d: RZ2,4,6-trimethyl
2e: RZH
2f: 1-naphthol
2g: RZ4-Cl
11ab
11ac
11ad
11ae
11af
11ag
11ah
11ai
83
76
76
82
64
70
43 (55)
61
2h: RZ4-F
2i: RZ4-acetyl
a The yields in parentheses are based on recovered starting material.

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M. Yoshida et al. / Tetrahedron 61 (2005) 4381–4393
Table 3. Reactions of various propargylic carbonates 1b–1d with p-methoxyphenol 2aa
Entry
1b
Substrate
Product
Yield (%)
64
1b
11ba
11ca
11da
2b
71
66
1c
3c
1d
a Reactions were carried out in the presence of 5 mol% Pd2(dba)3$CHCl3, 20 mol% ligand, and 1.1 equiv of p-methoxyphenol 2a in dioxane at 60 8C for 12–
24 h.
b dppf was used as a ligand.
c dppb was used as a ligand.
The results of the reactions of propargylic carbonates
1b–1d, possessing various substituents at the propargylic
position, with p-methoxyphenol (2a) were summarized in
Table 3. The methyl substituted compound 1b underwent
the reaction that formed the dihydrofuran 11ba in 64% yield
(entry 1). Reactions of pentyl- and phenyl-substituted
substrates 1c and 1d also afforded the corresponding
products 11ca and 11da in 71 and 66% yields, respectively
(entries 2 and 3). These results show that the regioselective
addition of phenol can proceed even in the presence of a
bulky substituent at the propargylic position.
We next examined the reaction of the substrate 1f carrying a
cyclohexane ring (Table 5). The substrate 1f reacted with
p-methoxyphenol (2a) in the presence of palladium catalyst
with dppf to give the trans-fused bicyclic product 11fa in
46% yield (entry 1). The low yield would reflect the
difficulties to construct the strained trans-product 11fa. The
similar results were observed by the reactions using dppb
and PPh3 (entries 2 and 3).
Table 5. Palladium-catalyzed reaction of cyclic substrate 1f with 2a
The reaction of propargylic carbonate 1e having no
substituent at the 2-position was then examined (Table 4).
When the palladium-catalyzed reaction of 1e with
p-methoxyphenol (2a) was carried out in the presence of
dppf at 60 8C, the corresponding product 11ea was
produced in 33% yield. It was found that the yield was
slightly increased by carrying out the reaction at 50 8C
(entry 2). Although bidentate ligands such as dppe, dppp
and dppb were not effective (entries 3–5), the yield was
improved to 47% by using Pd(PPh3)4 as the catalyst
(entry 6).10
Entry
Ligand
Yield (%)
1
dppf
dppb
PPh3
46
31
44
2
3a
a 10 mol% Pd(PPh3)4 was used as a palladium catalyst.
The reaction of 1g, possessing a latent nucleophilic
p-methoxyphenolic moiety as a part of the carbonate
leaving group, was then examined (Scheme 6). When 1g
was subjected to the palladium catalyzed reaction, the
corresponding dihydrofuran 11aa was provided in 73%
yield. On this reaction, the substrate initially releases the
phenoxide, which then acts as a nucleophile for the resulting
p-allyl complex to produce the product.
Table 4. Palladium-catalyzed reaction of unsubstituted substrate 1e with 2a
Entry
Ligand
Temperature
(8C)
Yield (%)
1
2
3
4
dppf
dppf
dppe
dppp
dppb
PPh3
60
50
50
50
50
50
33
39
11
30
36
47
5
6a
a 10 mol% Pd(PPh3)4 was used as a palladium catalyst.
Scheme 6.

M. Yoshida et al. / Tetrahedron 61 (2005) 4381–4393
4385
Scheme 7.
Initial attempts for the reactions of 1h with various phenols
failed, because the reactive phenolic hydroxy group would
also act as an additional nucleophile leading to the
formation of polymerized products. However, we were
delighted that the reaction successfully proceeded when
2-methyl-1,3-cyclohexanedione 2j was used as a nucleo-
phile (Table 6). The reaction of 1h with 2j in the presence of
5 mol% Pd2(dba)3$CHCl3 and 20 mol% dppe in dioxane at
60 8C was carried out, the substituted benzofuran 11hj was
obtained in 55% yield (entry 1). The reactions using other
bidentate ligands were also effective (entries 2–6), and the
yield was improved to 85% when 1,5-bis(diphenyl-
phosphino)pentane (dpppentane) was employed (entry 4).
Furthermore, it was clear that the monodentate ligands also
catalyzed the reactions (entries 7–9).10 The best yield was
obtained by the reaction using P(OPri)3 (87% yield in entry
9).
Scheme 8.
The reactions of 1h with 1,3-cyclopentanedione 2k were
next examined (Table 7). When 1h was subjected to the
palladium-catalyzed reaction with 2k, the corresponding
benzofuran 11hk was obtained (entry 1). Although the yield
was not high in the presence of dpppentane and P(OPri)3 (26
and 40% yields in entries 1 and 2), the desired product was
produced in 87% yield by the reaction with dppf (entry 3).
Table 6. Palladium-catalyzed reaction of 1h with 2-methyl-1,3-cyclo-
hexanedione 2j
We also attempted the reaction using dimethyl malonate (2l)
as a nucleophile (Scheme 9). Interestingly, when 2l was
used for the reaction with 1h, O-alkylated benzofuran 11hl
was obtained in 83% yield. The O-alkylated structure was
determined by the hydrolysis of the product to form a known
benzofuran-2-yl methanol (17). It was expected that in this
case the reaction would proceed via the regioselective
addition at the oxygen atom to the p-allyl complex 18 and
the hydrolysis of the resulting enol ether 19 during the
workup. It is not clear why the unusual O-alkylation occurs
prior to the C-alkylation, and several examples concerning
the regioselective O-alkylation of malonates to p-allyl-
palladium complexes have been previously reported.11
Entry
Ligand
Yield (%)
1
2
3
4
5
6
dppe
dppp
dppb
dpppentane
dpphexane
dppf
PPh3
P(OEt)3
P(OPri)3
55
50
83
85
81
77
84
52
87
7a
8b
9b
a 10 mol% Pd(PPh3)4 was used as a palladium catalyst.
b 40 mol% ligand was used.
Table 7. Palladium-catalyzed reaction of 1h with 2-methyl-1,3-cyclopen-
tanedione 2k
Our next attention was turned to the reactivity of the phenol-
substituted propargylic compounds since the formation of
the substituted benzofurans was anticipated (Scheme 7). It
was expected that the substituted benzofurans can be
synthesized from the reaction of the substrates with
nucelophiles. Preparation of the substrates was carried out
as follows (Scheme 8). The Sonogashira reaction of silyl-
protected iodophenol 15 with propargylalcohol yielded the
coupled product 16, whose reaction with methyl chloro-
formate followed by desilylation with TBAF lead to the
propargylic carbonate 1h. To examine the reactivity of
acetoxy group as a leaving group, the propargylic acetate 1i
was prepared from 16 in two steps.
Entry
Ligand
Yield (%)a
1
dpppentane
P(OPri)3
dppf
26
40 (49)
87
2b
3
a The yields in parentheses are based on recovered starting material.
b 40 mol% ligand was used.

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M. Yoshida et al. / Tetrahedron 61 (2005) 4381–4393
Scheme 9.
Finally, the reaction of 1i, having a propargylic acetoxy
group as a leaving group, was investigated (Scheme 10).
When the palladium-catalyzed reaction of 1i with 2j was
performed, the desired product 11hj was produced in 79%
yield. The result shows that the acetoxy group was also
effective as a leaving group in the reaction.
commercial suppliers and used without further purification
except when otherwise noted. Solvents were dried and
distilled according to standard protocols. The phrase
‘residue upon workup’ refers to the residue obtained when
the organic layer was separated and dried over anhydrous
MgSO4 and the solvent was evaporated under reduced
pressure. Compounds 6,13 7e14 and 1515 were prepared
according to the literature methods. All new compounds
were determined to be O95% pure by 1H NMR
spectroscopy.
4.1.1. 5-(4-Methoxybenzyloxy)-4,4-dimethyl-2-pentyn-1-
ol (7a). To a stirred solution of PPh3 (39.4 g, 150.2 mmol) in
CH2Cl2 (100 mL) was added CBr4 (24.9 g, 75.1 mmol) at
0 8C, and the reaction mixture was allowed to warm to rt.
After stirring was continued for 30 min, a solution of the
aldehyde 6 (5.56 g, 25.0 mmol) in CH2Cl2 (50 mL) was
added to the mixture at 0 8C, and stirring was continued for
7 h at rt. The resulting mixture was quenched with saturated
aqueous NaHCO3 and extracted with AcOEt. The combined
extracts were washed with brine, and the residue upon
workup was chromatographed on silica gel with AcOEt–
hexane (15:85 v/v) as eluent to give dibromide (8.0 g,
21.2 mmol, 85%) as a colorless oil. To a stirred solution of
the dibromide (3.58 g, 9.46 mmol) in THF (60 mL) was
added dropwise BuLi (13.2 mL, 1.59 M in hexane solution,
20.6 mmol) at K78 8C. After stirring was continued for 1 h
at the same temperature, and for an additional 1 h at rt, to the
reaction mixture was added paraformaldehyde (442 mg,
14.7 mmol) at K78 8C. The mixture was allowed to warm
to rt over a period of 2 h, and then stirred for 10 h at the
same temperature. The reaction mixture was diluted with
water and extracted with AcOEt. The residue upon workup
was chromatographed on silica gel with AcOEt–hexane
(30:70 v/v) as eluent to give propargylic alcohol 7a (2.30 g,
9.27 mmol, 98%) as a colorless oil; RfZ0.28 (AcOEt–
Scheme 10.
3. Conclusion
In conclusion, we have developed a methodology for the
synthesis of substituted 2,3-dihydrofurans and benzofurans
using a palladium catalyst. The reactions of propargylic
compounds having a hydroxyl group at the homo-
propargylic position with nucleophiles produce a variety
of dihydrofurans and benzofurans in one step. Recently,
much attention has been paid to the synthesis of natural
products containing these furan rings, which exhibit
potentially very interesting biological activities.12 Our
process could, therefore, provide an efficient protocol for
production of these molecules. Efforts to extend the scope of
these reactions and their consequent application to the
syntheses of natural products are currently in progress.
4. Experimental
4.1. General
1
hexaneZ3:7 v/v); H NMR (300 MHz, CDCl3) d 1.21 (s,
6H), 2.04 (br s, 1H), 3.27 (s, 2H), 3.80 (s, 3H), 4.23 (s, 2H),
4.53 (s, 2H), 6.88 (dt, JZ8.4, 3.0 Hz, 2H), 7.27 (dt, JZ8.4,
3.0 Hz, 2H); 13C NMR (75 MHz, CDCl3) d 25.9, 32.3, 51.2,
55.2, 73.0, 77.9, 78.6, 91.8, 113.8, 129.2, 130.5, 159.3; IR
All nonaqueous reactions were carried out under a positive
atmosphere of argon or nitrogen in dried glassware unless
otherwise indicated. Materials were obtained from

M. Yoshida et al. / Tetrahedron 61 (2005) 4381–4393
4387
(neat) 3381, 2968, 2930, 2866, 1514 cmK1; MS (EI) m/z
(relative intensity) 248 [MC, 1], 247 (1), 231 (1), 217 (18),
216 (1), 200 (2), 96 (1), 81 (1), 66 (1), 52 (1); HRMS (EI)
calcd for C15H20O3 [MC] 248.1412. Found 248.1390.
on silica gel with AcOEt–hexane (15:85 v/v) as eluent to
give the alcohol 7b (1.51 g, 5.76 mmol, 82% for 2 steps) as
a colorless oil; RfZ0.33 (AcOEt–hexaneZ3:7 v/v); 1H
NMR (400 MHz, CDCl3) d 1.20 (s, 6H), 1.41 (d, JZ6.6 Hz,
3H), 3.26 (s, 2H), 3.81 (s, 3H), 4.50 (q, JZ6.6 Hz, 1H), 4.52
(s, 3H), 6.87 (d, JZ8.8 Hz, 2H), 7.27 (d, JZ8.8 Hz, 2H);
13C NMR (100 MHz, CDCl3) d 24.7, 26.1, 32.3, 55.3, 58.5,
72.9, 82.2, 90.1, 113.6, 129.0, 130.5, 159.0; IR (neat) 3416,
2974, 2934, 2900, 2866, 2837, 1612, 1514, 1248 cmK1; MS
(EI) m/z (relative intensity) 262 [MC, 1], 261 (1), 247 (1),
245 (1), 230 (1), 217 (23), 215 (1), 163 (4), 149 (1), 137 (4),
135 (8), 122 (14), 121 (100), 106 (1), 90 (1), 79 (1), 64 (1),
50 (1); HRMS (EI) calcd for C16H22O3 [MC] 262.1569.
Found 262.1531.
4.1.2. 1-Methoxycarbonyloxy-5-(4-methoxybenzyloxy)-
4,4-dimethyl-2-pentyne (8a). To a stirred solution of
propargylic alcohol 7a (2.30 g, 9.82 mmol) and pyridine
(2.4 mL, 29.5 mmol) in CH2Cl2 (46 mL) was added
dropwise methyl chlorocarbonate (1.0 mL, 13.0 mmol) at
0 8C, and stirring was continued for 1 h at the same
temperature. The reaction mixture was diluted with water
and extracted with AcOEt. The combined extracts were
washed with saturated NH4Cl and brine. The residue upon
workup was chromatographed on silica gel with AcOEt–
hexane (15:85 v/v) as eluent to give the propargylic
carbonate 8a (2.65 g, 9.07 mmol, 92%) as a colorless oil;
4.1.5. 1-Methoxycarbonyloxy-5-(4-methoxybenzyloxy)-
1,4,4-trimethyl-2-pentyne (8b). By following the same
procedure described for 8a, the propargylic carbonate 8b
was prepared from the alcohol 7b in 95% yield on a
3.7 mmol scale; colorless oil; RfZ0.60 (AcOEt–hexaneZ
1
RfZ0.50 (AcOEt–hexaneZ3:7 v/v); H NMR (400 MHz,
CDCl3) d 1.21 (s, 6H), 3.27 (s, 2H), 3.79 (s, 3H), 3.81 (s,
3H), 4.52 (s, 2H), 4.74 (s, 2H), 6.88 (d, JZ7.8 Hz, 2H), 7.27
(d, JZ7.8 Hz, 2H); 13C NMR (75 MHz, CDCl3) d 25.8,
32.5, 55.0, 55.3, 56.3, 72.9, 73.4, 77.6, 93.7, 113.6, 129.0,
130.4, 155.1, 158.9; IR (neat) 2966, 2936, 2858, 1755,
1269 cmK1; MS (EI) m/z (relative intensity) [306 (MC), 1],
261 (3), 231 (3), 216 (1), 200 (6), 199 (21), 185 (4), 169 (1),
138 (1), 122 (15), 94 (1), 79 (9), 64 (1), 50 (1). Anal. Calcd
for C17H22O5: C, 66.65; H, 7.24. Found: C, 66.46; H, 7.11.
1
3:7 v/v); H NMR (600 MHz, CDCl3) d 1.20 (s, 6H), 1.50
(d, JZ6.6 Hz, 3H), 3.28 (s, 2H), 3.78 (s, 3H), 3.81 (s, 3H),
4.52 (s, 2H), 5.34 (q, JZ6.6 Hz, 1H), 6.88 (d, JZ8.6,
2.4 Hz, 2H), 7.27 (d, JZ8.6 Hz, 2H); 13C NMR (150 MHz,
CDCl3) d 21.9, 25.8, 32.3, 54.7, 55.2, 64.9, 72.9, 77.8, 77.9,
91.9, 113.7, 129.0, 130.6, 154.8, 159.1; IR (neat) 2966,
2934, 2856, 1765, 1747 1514, 1443, 1267 cmK1; MS (EI)
m/z (relative intensity) 320 [MC, 1], 245 (5), 230 (1), 217
(4), 214 (1), 213 (18), 205 (1), 199 (6), 183 (1), 151 (1), 137
(8), 136 (2), 122 (13), 121 (100), 108 (3), 106 (1), 92 (1), 90
(1), 80 (1), 56 (1), 53 (1); HRMS (EI) calcd for C18H24O5
[MC] 320.1624. Found 320.1657.
4.1.3. 5-Methoxycarbonyloxy-2,2-dimethyl-3-pentyn-1-
ol (1a). To a stirred solution of the MPM ether 8a (2.65 g,
9.07 mmol) in CH2Cl2 (50 mL) and H2O (5 mL) was added
DDQ (2.47 g, 10.9 mmol) at rt. After stirring was continued
for 1.5 h, the reaction mixture was diluted water, and
extracted with AcOEt. The combined extracts were washed
with brine, and the residue upon workup was chromato-
graphed on silica gel with AcOEt–hexane (30:70 v/v) as
eluent to give the alcohol 1a (1.67 g, 8.97 mmol, 99%) as a
colorless oil; RfZ0.23 (AcOEt–hexaneZ3:7 v/v); 1H NMR
(400 MHz, CDCl3) d 1.20 (s, 6H), 2.35 (br s, 1H), 3.41 (s,
2H), 3.81 (s, 3H), 4.73 (s, 2H); 13C NMR (100 MHz,
CDCl3) d 25.0, 34.2, 55.0, 56.0, 71.2, 74.7, 92.8, 155.0; IR
(neat) 3450, 2924, 2855, 1747, 1269 cmK1; MS (EI) m/z
(relative intensity) [155 (MKOMe)C, 6], 185 (1), 171 (1),
156 (2), 154 (1), 139 (1), 127 (1), 122 (1), 111 (5), 110 (1),
95 (4), 80 (100), 65 (5), 51 (2). Anal. Calcd for C9H14O4: C,
58.05; H, 7.58. Found: C, 57.83; H, 7.34.
4.1.6. 5-Methoxycarbonyloxy-2,2,5-trimethyl-3-pentyn-
1-ol (1b). By following the same procedure described for
1a, the alcohol 1b was prepared from the MPM ether 8b in
99% yield on a 3.6 mmol scale; colorless oil; RfZ0.28
1
(AcOEt–hexaneZ3:7 v/v); H NMR (400 MHz, CDCl3) d
1.19 (s, 6H), 1.51 (d, JZ6.8 Hz, 3H), 2.11 (br s, 1H), 3.38
(s, 2H), 3.79 (s, 3H), 5.29 (q, JZ6.6 Hz, 1H); 13C NMR
(100 MHz, CDCl3) d 21.7, 25.12, 25.14, 34.2, 54.8, 64.7,
71.4, 79.4, 90.9, 154.7; IR (neat) 3420, 2970, 2937, 2874,
1747, 1732, 1445, 1267 cmK1; MS (EI) m/z (relative
intensity) 169 [(MKOMe)C, 5], 185 (1), 141 (1), 136 (1),
125 (2), 124 (1), 110 (3), 108 (2), 97 (1), 93 (39), 92 (2), 85
(1), 78 (3), 73 (1), 63 (1), 58 (1), 50 (1), 43 (8), 42 (1). Anal.
Calcd for C10H16O4: C, 59.98; H, 8.05. Found: C, 59.81; H,
7.89.
4.1.4. 5-(4-Methoxybenzyloxy)-1,4,4-trimethyl-2-pen-
tyn-1-ol (7b). To a stirred solution of alcohol 7a (1.76 g,
7.07 mmol) in DMSO (15 mL), triethylamine (9 mL) and
CH2Cl2 (9 mL) was added sulfur trioxide pyridine complex
(4.50 g, 28.3 mmol) at rt. After stirring was continued for
19 h, the reaction mixture was diluted with water, and
extracted with AcOEt. The organic layers were washed with
brine, and the residue upon workup was chromatographed
on silica gel with AcOEt–hexane (15:85 v/v) as eluent to
give the aldehyde. To a stirred solution of the aldehyde in
THF (40 mL) was added dropwise MeLi (8.8 mL, 1.20 M in
Et2O solution, 10.6 mmol) at K78 8C. After stirring was
continued for 1 h at the same temperature, the reaction
mixture was quenched with water, and extracted with
AcOEt. The combined organic layers were washed with
brine, and the residue upon workup was chromatographed
4.1.7. 1-(4-Methoxybenzyloxy)-2,2-dimethyl-3-decyn-5-
ol (7c). To a stirred solution of alcohol 7a (1.11 g,
4.47 mmol) in DMSO (10 mL), triethylamine (6 mL) and
CH2Cl2 (6 mL) was added sulfur trioxide pyridine complex
(2.85 g, 17.9 mmol) at rt. After the mixture was stirred for
10.5 h, to the reaction mixture was diluted with water, and
extracted with AcOEt. The organic layers were washed with
brine, and the residue upon workup was chromatographed
on silica gel with AcOEt–hexane (15:85 v/v) as eluent to
give the aldehyde. To the stirred magnesium ribbon
(218 mg, 8.95 mmol) in THF (29 mL) was added n-amyl-
bromide (1.18 mL, 8.95 mmol) at 0 8C. After stirring was
continued for 1.5 h, the aldehyde in THF (10 mL) was added
at the same temperature. After stirring was continued for

4388
M. Yoshida et al. / Tetrahedron 61 (2005) 4381–4393
2 h, the reaction mixture was quenched with water and
extracted with AcOEt. The combined organic layers were
washed with brine, and the residue upon workup was
chromatographed on silica gel with AcOEt–hexane (15:85
v/v) as eluent to give the alcohol 7c (912 mg, 2.86 mmol,
64%) as a colorless oil; RfZ0.48 (AcOEt–hexaneZ3:7
v/v); 1H NMR (400 MHz, CDCl3) d 0.89 (t, JZ6.8 Hz, 3H),
1.12 (s, 6H), 1.29–1.34 (m, 4H), 1.36–1.42 (m, 2H), 1.59–
1.68 (m, 3H), 3.26 (s, 2H), 3.79 (s, 3H), 4.32 (dd, JZ11.0,
6.1 Hz, 1H), 4.52 (s, 2H), 6.87 (d, JZ8.6 Hz, 2H), 7.26 (d,
JZ8.6 Hz, 2H); 13C NMR (100 MHz, CDCl3) d 14.0, 22.6,
24.9, 26.1, 31.5, 32.3, 38.0, 55.2, 62.5, 72.9, 78.0, 81.5,
90.7, 113.6, 128.9, 130.4, 158.9; IR (neat) 3418, 2961, 2932,
2858, 1614, 1514, 1248 cmK1; MS (EI) m/z (relative
intensity) 318 [MC, 1], 301 (1), 287 (1), 286 (1), 270 (2),
244 (1), 230 (1), 217 (32), 211 (1), 197 (1), 182 (1), 167 (1),
163 (4), 138 (1), 137 (4), 122 (12), 121 (100), 110 (1), 108
(2), 107 (2), 92 (1), 91 (3), 78 (3), 66 (1), 42 (1); HRMS (EI)
calcd for C20H30O3 [MC] 318.2195. Found 318.2174.
was continued for 10 h, the reaction mixture was diluted
with water, and extracted with AcOEt. The organic layers
were washed with brine, and the residue upon workup was
chromatographed on silica gel with AcOEt–hexane (15:85
v/v) as eluent to give the aldehyde. To a stirred solution of
the aldehyde in THF (40 mL) was added dropwise PhMgBr
(5.8 mL, 1.03 M in THF solution, 5.82 mmol) at 0 8C. After
stirring was continued for 2 h at the same temperature, and
the reaction mixture was quenched with water and extracted
with AcOEt. The combined extracts were washed with
brine, and the residue upon workup was chromatographed
on silica gel with AcOEt–hexane (15:85 v/v) as eluent to
give the alcohol 7d (1.10 g, 3.38 mmol, 87%) as a colorless
oil; RfZ0.40 (AcOEt–hexaneZ3:7 v/v); 1H NMR
(400 MHz, CDCl3) d 1.24 (s, 6H), 2.44 (br s, 1H), 3.31 (s,
2H), 3.78 (s, 3H), 4.50 (s, 2H), 5.44 (s, 1H), 6.84 (dd, JZ
6.9, 2.0 Hz, 2H), 7.22–7.36 (m, 5H), 7.52–7.54 (m, 2H); 13C
NMR (100 MHz, CDCl3) d 26.1, 26.1, 32.6, 55.3, 64.6,
72.9, 80.0, 92.9, 113.6, 126.7, 128.0, 128.3, 128.9, 130.4,
141.1, 158.9; IR (neat) 3404, 2968, 2939, 2864, 2837, 1612,
1514, 1454, 1246 cmK1; MS (EI) m/z (relative intensity)
324 [MC, 2], 307 (2), 276 (1), 247 (1), 217 (22), 215 (3),
203 (2), 187 (3), 186 (1), 173 (5), 172 (1), 170 (3), 158 (1),
157 (3), 156 (4), 145 (1), 143 (1), 141 (2), 133 (1), 131 (1),
121 (100), 109 (3), 107 (4), 106 (2), 90 (1), 79 (2); HRMS
(EI) calcd for C21H24O3 [MC] 324.1725. Found 324.1735.
4.1.8. 5-Methoxycarbonyloxy-1-(4-methoxybenzyloxy)-
2,2-dimethyl-3-decyne (8c). By following the same
procedure described for 8a, the propargylic carbonate 8c
was prepared from the alcohol 7c in 97% yield on a
2.9 mmol scale; colorless oil; RfZ0.45 (AcOEt–hexaneZ
2:8 v/v); 1H NMR (400 MHz, CDCl3) d 0.88 (t, JZ6.9 Hz,
3H), 1.20 (s, 6H), 1.27–1.31 (m, 4H), 1.40–1.47 (m, 2H),
1.70–1.80 (m, 2H), 3.28 (s, 2H), 3.77 (s, 3H), 3.81 (s, 3H),
4.51 (s, 2H), 5.23 (t, JZ6.5 Hz, 1H), 6.85–6.88 (m, 2H),
7.25–7.27 (m, 2H); 13C NMR (150 MHz, CDCl3) d 13.9,
22.4, 24.5, 25.8, 31.2, 31.6, 32.4, 35.1, 54.7, 55.2, 68.7,
72.9, 77.9, 92.6, 113.7, 129.0, 130.7, 155.0, 159.0; IR (neat)
4.1.11. 1-Methoxycarbonyloxy-5-(4-methoxybenzyloxy)-
4,4-dimethyl-1-phenyl-2-pentyne (8d). By following the
same procedure described for 8a, the propargylic carbonate
8d was prepared from the alcohol 7d in 87% yield on a
3.4 mmol scale; colorless oil; RfZ0.38 (AcOEt–hexaneZ
2:8 v/v); 1H NMR (400 MHz, CDCl3) d 1.24 (s, 6H), 3.31 (s,
2H), 3.77 (s, 3H), 3.80 (s, 3H), 4.50 (s, 2H), 6.32 (s, 1H),
6.84 (dt, JZ8.6, 2.0 Hz, 2H), 7.22–7.22 (m, 2H), 7.32–7.35
(m, 3H), 7.52–7.55 (m, 2H); 13C NMR (100 MHz, CDCl3) d
25.8, 25.8, 32.7, 54.9, 55.3, 70.1, 72.9, 76.1, 77.8, 94.7,
113.6, 127.8, 128.5, 128.9, 130.5, 136.9, 154.8, 158.9; IR
(neat) 2968, 2934, 2855, 2845, 1755, 1747, 1614, 1514,
1258 cmK1; MS (EI) m/z (relative intensity) 382 [MC, 1],
307 (11), 305 (11), 292 (1), 276 (5), 274 (1), 246 (1), 231
(1), 230 (1), 219 (1), 217 (11), 207 (1), 200 (1), 198 (1), 186
(2), 178 (1), 170 (17), 168 (1), 156 (11), 154 (1), 153 (2),
151 (1), 141 (5), 139 (1), 138 (1), 137 (7), 126 (1), 121
(100), 114 (1), 107 (1), 102 (1), 90 (1), 75 (1), 59 (1), 56 (1);
HRMS (EI) calcd for C22H32O5 [MC] 382.1780. Found
382.1789.
2957, 2932, 2860, 1755, 1747, 1614, 1514, 1443, 1267 cmK1
;
MS (EI) m/z (relative intensity) 376 [MC, 1], 333 (1), 305
(1), 301 (10), 286 (2), 272 (1), 269 (33), 258 (1), 255 (3),
244 (7), 239 (1), 230 (2), 225 (1), 217 (12), 198 (1), 195 (1),
193 (1), 183 (1), 171 (1), 163 (1), 159 (1), 151 (1), 139 (1),
137 (9), 124 (1), 121 (100), 107 (6), 71 (1), 59 (2), 57 (1), 43
(2); HRMS (EI) calcd for C22H32O5 [MC] 376.2250. Found
376.2227.
4.1.9. 5-Methoxycarbonyloxy-2,2-dimethyl-3-decyn-1-ol
(1c). By following the same procedure described for 1a, the
alcohol 1c was prepared from the MPM ether 8c in 99%
yield on a 2.8 mmol scale; colorless oil; RfZ0.18 (AcOEt–
1
hexaneZ2:8 v/v); H NMR (400 MHz, CDCl3) d 0.89 (t,
JZ6.9 Hz, 3H), 1.19 (s, 6H), 1.26–1.35 (m, 4H), 1.40–1.44
(m, 2H), 1.72–1.83 (m, 2H), 2.06 (br s, 1H), 3.38 (s, 2H),
3.79 (s, 3H), 5.19 (t, JZ6.6 Hz, 1H); 13C NMR (100 MHz,
CDCl3) d 13.9, 22.4, 24.6, 25.15, 25.18, 31.2, 34.3, 34.9,
54.8, 68.6, 71.4, 78.6, 91.6, 154.9; IR (neat) 3443, 2953,
2932, 2872, 1747, 1445, 1267 cmK1; MS (EI) m/z (relative
intensity) 279 [(MCNa)C, 1], 241 (1), 225 (3), 197 (1), 183
(1), 181 (2), 180 (1), 171 (1), 164 (1), 150 (100), 135 (23),
120 (1), 112 (1), 108 (9), 96 (4), 84 (1), 71 (2), 57 (4), 43
(12). Anal. Calcd for C14H24O4: C, 65.60; H, 9.44. Found:
C, 65.31; H, 9.27.
4.1.12. 1-Methoxycarbonyloxy-4,4-dimethyl-1-phenyl-2-
pentyn-1-ol (1d). By following the same procedure
described for 1a, the alcohol 1d was prepared from the
MPM ether 8d in quantitative yield on a 3.0 mmol scale;
colorless oil; RfZ0.25 (AcOEt–hexaneZ3:7 v/v); 1H NMR
(400 MHz, CDCl3) d 1.23 (s, 3H), 1.23 (s, 3H), 1.91 (br s,
1H), 3.43 (s, 2H), 3.79 (s, 3H), 6.28 (s, 1H), 7.35–7.40 (m,
3H), 7.51–7.53 (m, 2H); 13C NMR (100 MHz, CDCl3) d
25.10, 25.13, 34.5, 55.0, 70.0, 71.4, 77.7, 93.7, 127.6, 128.6,
129.1, 154.8; IR (neat) 3420, 2970, 2932, 2872, 1755, 1747,
1732, 1454, 1443, 1325, 1258 cmK1; MS (EI) m/z (relative
intensity) 262 [MC, 3], 247 (7), 203 (11), 187 (15), 186 (8),
172 (29), 170 (2), 169 (10), 168 (16), 165 (2), 157 (32), 156
(100), 154 (9), 153 (12), 142 (15), 130 (5), 126 (2), 118 (3),
114 (2), 91 (14), 85 (23), 79 (3), 59 (6), 47 (7), 43 (5). Anal.
4.1.10. 5-(4-Methoxybenzyloxy)-4,4-dimethyl-1-phenyl-
2-pentyn-1-ol (7d). To a stirred solution of alcohol 7a
(963 g, 3.88 mmol) in DMSO (10 mL), triethylamine
(6 mL) and CH2Cl2 (6 mL) was added sulfur trioxide
pyridine complex (2.47 g, 15.5 mmol) at rt. After stirring

M. Yoshida et al. / Tetrahedron 61 (2005) 4381–4393
4389
Calcd for C15H18O4: C, 68.68; H, 6.92. Found: C, 68.72; H,
6.92.
(relative intensity) [153 (MKH)C, 1], 137 (1), 136 (11),
123 (1), 122 (5), 111 (1), 110 (1), 99 (1), 98 (4), 97 (3), 96
(3), 92 (89), 91 (100), 87 (1), 86 (1), 82 (6), 81 (22), 80 (31),
78 (32), 74 (1), 73 (1), 69 (9), 67 (29), 64 (2), 57 (21), 56 (5),
55 (31), 51 (11), 44 (8), 43 (23); HRMS (EI) calcd for
C9H13O2 [(MKH)C] 153.0921, found 153.0901.
4.1.13. 1-Methoxycarbonyloxy-5-(4-methoxybenzyloxy)-
2-pentyne (8e). By following the same procedure described
for 8a, the propargylic carbonate 8e was prepared from the
alcohol 7e in 77% yield on a 9.5 mmol scale; colorless oil;
1
RfZ0.45 (AcOEt–hexaneZ3:7 v/v); H NMR (400 MHz,
4.1.16. (1R*,2R*)-2-(1-Methoxycarbonyloxy-2-pentyn)-
cyclohexan-1-ol (1f). By following the same procedure
described for 8a, the propargylic carbonate 1f was prepared
from the alcohol 10 in 78% yield on a 6.0 mmol scale;
colorless oil; RfZ0.50 (AcOEt–hexaneZ1:1 v/v); 1H NMR
(400 MHz, CDCl3) d 1.12–1.42 (m, 4H), 1.63–1.67 (m, 1H),
1.73–1.76 (m, 1H), 1.95–2.03 (m, 2H), 2.23–2.29 (m, 1H),
2.55 (br s, 1H), 3.46 (ddd, JZ19.2, 9.8, 4.1 Hz, 1H), 3.81 (s,
3H), 4.74 (d, JZ2.0 Hz, 2H); 13C NMR (100 MHz, CDCl3)
d 24.1, 24.7, 30.7, 33.2, 38.9, 55.0, 56.1, 73.2, 75.6, 89.4,
155.1; IR (neat) 3418, 2936, 2860, 1767, 1755, 1747, 1730,
1450, 1447, 1267 cmK1; MS (EI) m/z (relative intensity)
212 [MC, 1], 153 (1), 137 (14), 123 (1), 111 (1), 110 (1),
106 (1), 99 (1), 98 (1), 97 (6), 94 (32), 93 (69), 92 (100), 86
(1), 85 (2), 84 (12), 82 (7), 73 (1), 69 (7), 67 (31), 59 (18), 57
(17), 56 (4), 43 (24), 42 (4). Anal. Calcd for C11H16O4: C,
62.25; H, 7.60. Found: C, 62.11; H, 7.44.
CDCl3) d 2.52 (t, JZ6.8 Hz, 2H), 3.55 (t, JZ6.8 Hz, 2H),
3.80 (s, 6H), 4.47 (s, 2H), 4.72 (s, 2H), 6.87 (d, JZ8.5 Hz,
2H), 7.26 (d, JZ8.5 Hz, 2H); 13C NMR (100 MHz, CDCl3)
d 20.3, 55.0, 55.3, 56.1, 67.6, 72.6, 74.5, 85.1, 113.8, 129.3,
129.3, 130.0, 159.1; IR (neat) 3003, 2957, 2910, 2862, 2837,
1755, 1514, 1445, 1265 cmK1; MS (EI) m/z (relative
intensity) [278 (MC), 7], 191 (1), 153 (1), 151 (1), 137
(7), 127 (1), 121 (100), 109 (2), 107 (2), 95 (1), 89 (2), 59
(3); HRMS (EI) calcd for C15H18O5 [MC] 278.1154, found
278.1137. Anal. Calcd for C15H18O5: C, 64.74; H, 6.52.
Found: C, 64.69; H, 6.54.
4.1.14. 5-Methoxycarbonyloxy-3-pentyn-1-ol (1e). By
following the same procedure described for 1a, the alcohol
1e was prepared from the MPM ether 8e in 98% yield on a
3.6 mmol scale; colorless oil; RfZ0.33 (AcOEt–hexaneZ
1:1 v/v); 1H NMR (400 MHz, CDCl3) d 1.84 (br s, 1H), 2.51
(tt, JZ6.1, 2.2 Hz, 2H), 3.73 (dt, JZ11.8, 6.1 Hz, 2H), 3.81
(s, 3H), 4.73 (t, JZ2.2 Hz, 2H); 13C NMR (100 MHz,
CDCl3) d 23.1, 55.1, 56.0, 60.7, 75.4, 85.0, 155.2; IR (neat)
3371, 2959, 2881, 1755, 1747, 1447, 1269 cmK1; MS (EI)
m/z (relative intensity) [158 (MC), 1], 159 (1), 157 (1), 143
(1), 141 (1), 127 (10), 113 (1), 111 (1), 101 (1), 99 (10), 98
(1), 89 (1), 83 (28), 82 (8), 71 (3), 70 (1), 66 (2), 59 (19), 52
(100), 43 (33); HRMS (EI) calcd for C7H10O4 [MC]
158.0579, found 158.0541. Anal. Calcd for C7H10O4: C,
53.16; H, 6.37. Found: C, 53.20; H, 6.38.
4.1.17. 1-(4-Methoxyphenoxycarbonyloxy)-5-(4-methoxy-
benzyloxy)-4,4-dimethyl-2-pentyne (8g). By following the
same procedure described for 8a, the propargylic carbonate
8g was quantitatively prepared from the alcohol 7a with
4-methoxyphenyl chloroformate on a 2.6 mmol scale;
colorless oil; RfZ0.53 (AcOEt–hexaneZ3:7 v/v); 1H
NMR (400 MHz, CDCl3) d 1.23 (s, 6H), 3.29 (s, 2H), 3.78
(s, 3H), 3.79 (s, 3H), 4.53 (s, 2H), 4.83 (s, 2H), 6.85–6.91
(m, 3H), 7.07 (d, JZ9.1 Hz, 2H), 7.17 (d, JZ9.1 Hz, 1H),
7.27 (d, JZ8.3 Hz, 2H); 13C NMR (100 MHz, CDCl3) d
25.8, 32.6, 55.2, 55.6, 55.8, 65.8, 72.9, 73.1, 77.6, 94.2,
113.6, 114.34, 114.39, 121.6, 121.7 129.0, 130.4, 144.51,
144.55, 153.4, 157.3, 157.4, 159.0; IR (neat) 2968, 2936,
2909, 2860, 2837, 1776, 1771, 1759, 1614, 1514, 1504,
1234 cmK1; MS (EI) m/z (relative intensity) [398 (MC), 4],
231 (7), 184 (1), 151 (1), 149 (2), 138 (1), 137 (5), 135 (2),
124 (20), 121 (100), 108 (1), 96 (1), 80 (2), 66 (1), 54 (1);
HRMS (EI) calcd for C23H26O6 [MC] 398.1729. Found
398.1714.
4.1.15. (1R*,2R*)-2-(3-Hydroxy-1-pentynyl)cyclohexan-
1-ol (10). To a stirred solution of tetrahydro-2-(2-propynyl-
oxy)-2H-pyrane (3.1 mL, 21.8 mmol) and BF3$Et2O
(3.3 mL, 26.1 mmol) in THF (190 mL) was added dropwise
n-BuLi (15.3 mL, 1.59 M in hexane solution, 23.9 mmol) at
K78 8C. After stirring was continued for 1 h, cyclohexene
oxide (2.14 g, 21.8 mmol) in THF (10 mL) was added
dropwise to the reaction mixture, and stirring was continued
for an additional 1 h at the same temperature. The reaction
mixture was quenched with water, and the resulting mixture
was extracted with AcOEt. The combined extracts were
washed with satd NH4Cl and brine, and the residue upon
workup was used for next step without further purification.
To a stirred solution of the above residue in MeOH (50 mL)
was added TsOH$H2O (20 mg) at rt, and stirring was
continued for 10 h at 50 8C. The mixture was diluted with
water, and extracted with AcOEt. The combined extracts
were washed with brine, and the residue upon workup was
chromatographed on silica gel with AcOEt–hexane (40:60
v/v) as eluent to give the diol 10 (2.07 g, 18.0 mmol, 83%)
4.1.18. 5-(4-Methoxyphenoxycarbonyloxy)-2,2-dimethyl-
3-pentyn-1-ol (1g). By following the same procedure
described for 1a, the alcohol 1g was prepared from the
MPM ether 8g in 73% yield on a 0.64 mmol scale; colorless
oil; RfZ0.20 (AcOEt–hexaneZ3:7 v/v); 1H NMR
(400 MHz, CDCl3) d 1.21 (s, 6H), 2.25 (br s, 1H), 3.41 (s,
2H), 3.81 (s, 3H), 4.82 (s, 2H), 6.87 (dd, JZ6.8, 2.2 Hz,
2H), 7.08 (dd, JZ6.8, 2.2 Hz, 2H); 13C NMR (100 MHz,
CDCl3) d 25.0, 34.2, 55.50, 55.59, 71.2, 74.4, 93.4, 114.3,
121.6, 144.4, 153.4, 157.3; IR (neat) 3418, 2970, 2936,
1
as a colorless oil; RfZ0.25 (AcOEt–hexaneZ1:1 v/v); H
2872, 2839, 1767, 1761, 1610, 1510, 1504, 1242, 1205 cmK1
;
NMR (400 MHz, CDCl3) d 1.11–1.42 (m, 4H), 1.63–1.68
(m, 1H), 1.74–1.77 (m, 1), 1.94–2.05 (m, 2H), 2.21–2.26 (m,
1H), 2.98 (br s, 2H), 3.46 (ddd, JZ20.2, 3.8, 9.8 Hz, 1H),
4.26 (d, JZ1.4 Hz, 2H); 13C NMR (100 MHz, CDCl3) d
24.4, 24.9, 31.2, 33.6, 39.0, 51.1, 73.6, 80.3, 87.5; IR (neat)
3317, 2936, 2858, 1450, 1065, 1013 cmK1; MS (EI) m/z
MS (EI) m/z (relative intensity) [278 (M)C, 21], 279 (4),
247 (4), 170 (1), 167 (1), 135 (1), 126 (1), 125 (11), 124
(100), 123 (26), 110 (2), 107 (3), 97 (1), 96 (1), 94 (2), 84
(1), 80 (28), 73 (1), 68 (1), 57 (2), 56 (1), 43 (12), 42 (1);
HRMS (EI) calcd for C15H18O5 [MC] 278.1154. Found
278.1138.

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M. Yoshida et al. / Tetrahedron 61 (2005) 4381–4393
4.2. General procedure for the reactions of 5-methoxy-
carbonyloxy-3-pentyn1-ols with phenols. Reaction of 1a
with 2a
4.2.5. 3,3-Dimethyl-5-phenoxymethyl-2,3-dihydrofuran
(11ae). Yield 82%; colorless oil; RfZ0.73 (AcOEt–
hexaneZ3:7 v/v); H NMR (400 MHz, CDCl3) d 1.15 (s,
1
6H), 4.07(s, 2H), 4.51(s, 2H), 4.93(s, 1H), 6.93–6.97 (m, 3H),
7.27 (t, JZ8.0 Hz, 2H); 13C NMR (100 MHz, CDCl3) d 27.7,
43.2, 63.3, 83.1, 110.4, 114.8, 121.0, 129.3, 151.8, 158.4; IR
(neat)2959, 2928, 2868, 1599, 1495, 1238 cmK1; MS (EI) m/z
(relative intensity) 204 [MC, 100], 189 (35), 174 (1), 127 (1),
111 (57), 96 (19), 81 (22), 65 (20), 51 (11); HRMS (EI) calcd
for C13H16O2 [MC] 204.1150. Found 204.1128.
To a stirred solution of the propargylic carbonate 1a
(38.7 mg, 0.208 mmol) in dioxane (2 mL) were added
p-methoxyphenol (2a) (28.4 mg, 0.229 mmol), Pd2(dba)3$
CHCl3 (10.8 mg, 10.4 mmol) and dppf (23.0 mg, 41.6 mmol)
in sealed tube at rt. After the stirring was continued for 17 h
at 60 8C, the reaction mixture was concentrated. The residue
was chromatographed on silica gel with AcOEt–hexane
(2:98 v/v) as eluent to give the 2,3-dihydrofuran 11aa
(41 mg, 0.175 mmol, 84%) as colorless crystals (entry 4 in
Table 1).
4.2.6. 3,3-Dimethyl-5-(1-naphthoxymethyl)-2,3-dihydro-
furan (11af). Yield 64%; colorless oil; RfZ0.75 (AcOEt–
1
hexaneZ3:7 v/v); H NMR (400 MHz, CDCl3) d 1.17 (s,
6H), 4.09 (s, 2H), 4.70 (s, 2H), 5.01 (s, 1H), 6.84 (d, JZ
7.5 Hz, 1H), 7.33–7.49 (m, 4H), 7.76–7.80 (m, 1H), 8.29–
8.32 (m, 1H); 13C NMR (100 MHz, CDCl3) d 27.8, 43.2,
63.8, 83.2, 105.4, 109.9, 120.6, 122.1, 125.1, 125.6, 125.7,
126.3, 127.3, 134.4, 152.0, 154.2; IR (neat) 3053, 2953,
2930, 2866, 1581, 1462, 1269 cmK1; MS (EI) m/z (relative
intensity) 254 [MC, 100], 239 (17), 224 (2), 127 (28), 111
(15), 96 (2), 81 (5), 65 (3), 51 (3); HRMS (EI) calcd for
C17H18O2 [MC] 254.1307. Found 254.1310.
4.2.1. 3,3-Dimethyl-5-(4-methoxyphenoxymethyl)-2,3-
dihydrofuran (11aa). RfZ0.70 (AcOEt–hexaneZ3:7
v/v); mp 28–29 8C; H NMR (300 MHz, CDCl3) d 1.15 (s,
1
6H), 3.76 (s, 3H), 4.07 (s, 2H), 4.46 (s, 2H), 4.91 (s, 1H),
6.82 (dt, JZ9.3, 2.8 Hz, 2H), 6.89 (dt, JZ9.3, 2.8 Hz, 2H);
13C NMR (75 MHz, CDCl3) d 27.6, 43.0, 55.6, 64.2, 83.1,
110.5, 114.6, 116.1, 152.3, 152.9, 154.3; IR (KBr) 2866,
1506, 1229 cmK1; MS (EI) m/z (relative intensity) 234
[MC, 75], 219 (4), 111 (46), 96 (4), 81 (9), 65 (3), 51 (2);
HRMS (EI) calcd for C14H18O3 [MC] 234.1256. Found
234.1275.
4.2.7. 5-(4-Chlorophenoxymethyl)-3,3-dimethyl-2,3-
dihydrofuran (11ag). Yield 70%; colorless crystals; RfZ
1
0.75 (AcOEt–hexaneZ3:7 v/v); mp 38–39 8C; H NMR
4.2.2. 3,3-Dimethyl-5-(2-methoxyphenoxymethyl)-2,3-
dihydrofuran (11ab). Yield 83%; colorless crystals; RfZ
0.65 (AcOEt–hexaneZ3:7 v/v); mp 31–32 8C; H NMR
(400 MHz, CDCl3) d 1.15 (s, 6H), 4.06 (s, 2H), 4.49 (s, 2H),
4.92 (s, 1H), 6.85–6.89 (m, 2H), 7.20–7.25 (m, 2H); 13C
NMR (100 MHz, CDCl3) d 27.7, 43.2, 63.7, 83.1, 110.8,
116.1, 125.9, 129.2, 151.4, 157.0; IR (KBr) 2959, 2924,
2868, 1493, 1238 cmK1; MS (EI) m/z (relative intensity)
238 [MC, 85], 240 (30), 225 (5), 223 (15), 203 (11), 127 (6),
111 (100), 96 (22), 81 (28), 65 (9), 51 (4); HRMS (EI) calcd
for C13H15O2Cl [MC] 238.0761. Found 238.0725.
1
(400 MHz, CDCl3) d 1.13 (s, 6H), 3.87 (s, 3H), 4.05 (s, 2H),
4.58 (s, 2H), 4.91 (s, 1H), 6.92 (m, 4H); 13C NMR
(100 MHz, CDCl3) d 27.7, 55.8, 64.6, 83.1, 110.4, 111.9,
114.9, 120.7, 121.8, 147.9, 149.9, 152.0; IR (KBr) 2957,
2930, 2866, 1504, 1251 cmK1; MS (EI) m/z (relative
intensity) 234 [MC, 53], 219 (6), 203 (3), 111 (78), 96
(10), 81 (23), 65 (11), 51 (7). Anal. Calcd for C14H18O3: C,
71.77; H, 7.74. Found: C, 71.78; H, 7.67.
4.2.8. 5-(4-Fluorophenoxymethyl)-3,3-dimethyl-2,3-
dihydrofuran (11ah). Yield 43% (55% based on recovered
starting material); colorless crystals; RfZ0.75 (AcOEt–
hexaneZ3:7 v/v); mp 52–53 8C; 1H NMR (400 MHz,
CDCl3) d 1.15 (s, 6H), 4.06 (s, 2H), 4.47 (s, 2H), 4.91 (s,
1H), 6.86–6.98 (m, 4H); 13C NMR (100 MHz, CDCl3) d
27.7, 43.2, 64.1, 83.1, 110.7, 115.5, 115.8, 115.9, 116.0,
151.6, 154.5, 156.2, 158.5; IR (KBr) 2959, 2934, 2868,
1504, 1205 cmK1; MS (EI) m/z (relative intensity) 222
[MC, 100], 207 (17), 192 (1), 127 (1), 111 (65), 96 (16), 81
(18), 65 (3), 51 (1); HRMS (EI) calcd for C13H15O2F [MC]
222.1056. Found 222.1034.
4.2.3. 3,3-Dimethyl-5-(4-methyphenoxymethyl)-2,3-
dihydrofuran (11ac). Yield 76%; colorless needle; RfZ
1
0.75 (AcOEt–hexaneZ3:7 v/v); mp 44–45 8C; H NMR
(400 MHz, CDCl3) d 1.15 (s, 6H), 2.28 (s, 3H), 4.07 (s, 2H),
4.48 (s, 2H), 4.92 (s, 1H), 6.84 (d, JZ8.5 Hz, 2H), 7.06 (d,
JZ8.5 Hz, 2H); 13C NMR (100 MHz, CDCl3) d 20.5, 27.7,
43.1, 63.6, 83.1, 110.3, 114.7, 129.7, 130.2, 152.0, 156.3; IR
(KBr) 2953, 2918, 2882, 2862, 1518, 1498, 1460,
1250 cmK1; MS (EI) m/z (relative intensity) 218 [MC,
54], 203 (8), 188 (1), 127 (1), 111 (52), 96 (11), 81 (19), 65
(16), 51 (8); HRMS (EI) calcd for C14H18O2 [MC]
218.1307. Found 218.1301.
4.2.9. 5-(4-Acetylphenoxymethyl)-3,3-dimethyl-2,3-di-
hydrofuran (11ai). Yield 61%; colorless oil; RfZ0.50
1
(AcOEt–hexaneZ3:7 v/v); H NMR (400 MHz, CDCl3) d
1.16 (s, 6H), 2.55 (s, 3H), 4.07 (s, 2H), 4.58 (s, 2H), 4.95 (s,
1H), 6.97 (d, JZ8.7 Hz, 2H), 7.92 (d, JZ8.7 Hz, 2H); 13C
NMR (100 MHz, CDCl3) d 26.4, 27.7, 43.2, 63.3, 83.2,
111.0, 114.4, 130.4, 130.5, 151.0, 162.2, 196.6; IR (neat)
4.2.4. 3,3-Dimethyl-5-(2,4,6-trimethyphenoxymethyl)-
2,3-dihydrofuran (11ad). Yield 76%; colorless oil; RfZ
0.80 (AcOEt–hexaneZ3:7 v/v); 1H NMR (400 MHz,
CDCl3) d 1.16 (s, 6H), 2.23 (s, 3H), 2.26 (s, 6H), 4.08 (s,
2H), 4.25 (s, 2H), 4.92 (s, 1H), 6.80 (d, JZ0.5 Hz, 2H); 13C
NMR (100 MHz, CDCl3) d 16.2, 20.7, 27.8, 43.1, 67.2,
83.1, 110.5, 129.2, 130.6, 133.1, 152.3, 153.4; IR (neat)
2957, 2924, 2866, 1485, 1462, 1215 cmK1; MS (EI) m/z
(relative intensity) 246 [MC, 96], 231 (5), 216 (1), 201 (1),
119 (4), 111 (67), 96 (4), 81 (9), 65 (4), 51 (1); HRMS (EI)
calcd for C16H22O2 [MC] 246.1620. Found 246.1612.
2961, 2932, 2868, 1682, 1675 1599, 1460, 1360, 1259 cmK1
;
MS (EI) m/z (relative intensity) 246 [MC, 100], 231 (27),
216 (6), 109 (11), 94 (1), 81 (20), 65 (6), 51 (2); HRMS (EI)
calcd for C15H18O3 [MC] 246.1256. Found 246.1246.
4.2.10. 3,3-Dimethyl-5-(4-methoxyphenoxy-1-ethyl)-2,3-
dihydrofuran (11ba). Yield 64%; colorless oil; RfZ0.75

M. Yoshida et al. / Tetrahedron 61 (2005) 4381–4393
4391
1
(AcOEt–hexaneZ3:7 v/v); H NMR (400 MHz, CDCl3) d
needles; RfZ0.65 (AcOEt–hexaneZ3:7 v/v); 1H NMR
(400 MHz, CDCl3) d 0.92–1.45 (m, 4H), 1.68–1.77 (m, 1H),
1.84–1.88 (m, 1H), 1.99–2.01 (m, 1H), 2.21–2.25 (m, 1H),
2.42–2.49 (m, 1H), 3.67 (ddd, JZ14.8, 11.8, 3.4 Hz, 1H),
3.76 (s, 3H), 4.38–4.53 (m, 2H), 5.19 (s, 1H), 6.80–6.83 (m,
2H), 6.87–6.91 (m, 2H); 13C NMR (100 MHz, CDCl3) d
24.8, 25.8, 29.5, 30.5, 55.7, 64.7, 90.1, 106.3, 114.4, 114.5,
116.0, 118.5, 152.6, 154.0, 155.1; IR (neat) 2936, 2860,
2831, 1510, 1504, 1234, 1227 cmK1; MS (EI) m/z (relative
intensity) 260 [MC, 73], 177 (1), 175 (1), 165 (1), 164 (4),
149 (2), 137 (100), 123 (18), 107 (21), 83 (1), 69 (4), 57 (2),
42 (1), 41 (14); HRMS (EI) calcd for C16H20O3 [MC]
260.1412. Found 260.1395.
1.10 (s, 6H), 1.47 (d, JZ6.6 Hz, 3H), 3.76 (s, 3H), 4.01 (dd,
JZ12.6, 8.5 Hz, 2H), 4.65 (q, JZ6.6 Hz, 1H), 4.76 (s, 1H),
6.77–6.81 (m, 2H), 6.87–6.91 (m, 2H); 13C NMR
(100 MHz, CDCl3) d 19.3, 27.70, 27.72, 43.0, 55.7, 71.3,
82.9, 108.0, 114.3, 117.7, 151.9, 154.1, 156.2; IR (neat)
2957, 2936, 2870, 1504, 1229 cmK1; MS (EI) m/z (relative
intensity) 248 [MC, 25], 233 (1), 161 (1), 148 (1), 135 (2),
125 (48), 123 (9), 109 (50), 107 (3), 97 (4), 96 (1), 94 (1), 82
(1), 80 (1), 79 (4), 68 (1), 67 (8), 64 (1), 55 (21), 54 (1), 52
(1), 43 (20), 42 (1), 39 (3); HRMS (EI) calcd for C15H20O3
[MC] 248.1412. Found 248.1383.
4.2.11. 3,3-Dimethyl-5-(4-methoxyphenoxy-1-hexyl)-2,3-
dihydrofuran (11ca). Yield 71%; colorless oil; RfZ0.75
(AcOEt–hexaneZ3:7 v/v); H NMR (400 MHz, CDCl3) d
4.2.15. 4,4-Dimethyl-2-hydroxymethyltetrahydrofuran
(12). To a stirred solution of the 2,3-dihydrofuran 11aa
(158 mg, 0.678 mmol) in MeOH (12 mL) was added
10 wt% of Pd–C (10 mg) under 1 atm of hydrogen at rt,
and stirring was continued for 13 h. After filteration and
evaporation of the reaction mixture, the residue was
chromatographed on silica gel with AcOEt–hexane (20:80
v/v) as eluent to give the tetrahydrofuran (147 mg,
0.622 mmol, 92%). To a stirred solution of the tetra-
hydrofuran (45 mg, 0.190 mmol) and pyridine (23 mL,
0.286 mmol) in MeCN (7.5 mL) and water (1.9 mL) were
added ammonium cerium(IV) nitrate (251 mg, 0.457 mmol)
at 0 8C. After stirring was continued for 2 h at the same
temperature, the reaction mixture was diluted with water,
and extracted with Et2O. The combined extracts were
washed with satd NaHCO3 and brine, and the residue upon
workup was chromatographed on silica gel with AcOEt–
hexane (30:70 v/v) as eluent to give the alcohol 12 (8 mg,
0.0615 mmol, 32%) as a colorless oil. The spectrum data of
12 was in complete agreement with that of an authentic
sample.6
1
0.88 (t, JZ6.9 Hz, 3H), 1.078 (s, 3H), 1.083 (s, 3H), 1.23–
1.51 (m, 6H), 1.76–1.84 (m, 2H), 3.75 (s, 3H), 3.98 (dd, JZ
14.4, 8.3 Hz, 2H), 4.45 (t, JZ6.5 Hz, 1H), 4.74 (s, 1H),
6.78–6.81 (m, 2H), 6.86–6.89 (m, 2H); 13C NMR
(100 MHz, CDCl3) d 14.1, 22.6, 25.1, 27.6, 27.8, 31.6,
33.5, 43.0, 55.7, 75.7, 82.8, 109.0, 114.3, 117.5, 152.4,
154.0, 155.1; IR (neat) 2955, 2930, 2870, 1506, 1227 cmK1
;
MS (EI) m/z (relative intensity) 304 [MC, 27], 182 (5), 181
(36), 166 (15), 152 (1), 151 (7), 139 (1), 138 (3), 135 (2),
126 (1), 124 (30), 123 (20), 110 (2), 108 (1), 107 (4), 96 (2),
84 (1), 80 (1), 71 (3), 67 (6), 57 (3), 55 (17), 43 (10), 42 (1);
HRMS (EI) calcd for C19H28O3 [MC] 304.2038. Found
304.2011.
4.2.12. 3,3-Dimethyl-5-(4-methoxyphenoxy-1-benzyl)-
2,3-dihydrofuran (11da). Yield 66%; colorless crystals;
1
RfZ0.73 (AcOEt–hexaneZ3:7 v/v); mp 109–110 8C; H
NMR (400 MHz, CDCl3) d 1.10 (s, 3H), 1.11 (s, 3H), 3.73
(s, 3H), 4.02 (dd, JZ15.2, 8.3 Hz, 2H), 4.80 (s, 1H), 5.51 (s,
1H), 6.75 (d, JZ9.0 Hz, 2H), 6.88 (d, JZ9.0 Hz, 2H), 7.28–
7.36 (m, 3H), 7.45 (d, JZ7.1 Hz, 2H); 13C NMR (100 MHz,
CDCl3) d 27.6, 27.7, 43.0, 55.6, 77.3, 83.2, 110.2, 114.3,
117.5, 127.0, 128.0, 128.3, 138.4, 152.0, 154.1, 154.9; IR
(KBr) 2957, 2939, 2866, 1504, 1225 cmK1; MS (EI) m/z
(relative intensity) 310 [MC, 4], 187 (100), 172 (6), 170 (1),
160 (1), 155 (1), 142 (2), 130 (3), 123 (3), 118 (2), 110 (1),
107 (1), 106 (1), 95 (2), 90 (1), 80 (1), 77 (3), 67 (1), 51 (1);
HRMS (EI) calcd for C20H22O3 [MC] 310.1569. Found
310.1546.
4.3. Procedure for the palladium-catalyzed reaction of
1g (Scheme 6)
To a stirred solution of the propargylic carbonate 1g
(36.4 mg, 99.9 mmol) in dioxane (1 mL) were added
Pd2(dba)3$CHCl3 (5.2 mg, 4.99 mmol) and dppf (11 mg,
20.0 mmol) in sealed tube at rt. After the stirring was
continued for 11 h at 60 8C, the reaction mixture was
concentrated. The residue was chromatographed on silica
gel with AcOEt–hexane (2:98 v/v) as eluent to give the 2,3-
dihydrofuran 11aa (17 mg, 72.6 mmol, 73%) as colorless
crystals.
4.2.13. 5-(4-Methoxyphenoxymethyl)-2,3-dihydrofuran
(11ea). Yield 47%; colorless needles; RfZ0.70 (AcOEt–
hexaneZ3:7 v/v); mp 35–36 8C; 1H NMR (400 MHz,
CDCl3) d 2.68 (dt, JZ9.5, 1.0 Hz, 2H), 3.76 (s, 3H), 4.43
(t, JZ9.5 Hz, 2H), 4.48 (d, JZ1.0 Hz, 2H), 5.01 (s, 1H),
6.82 (dt, JZ9.5, 2.5 Hz, 2H), 6.89 (dt, JZ9.5, 2.5 Hz, 2H);
13C NMR (100 MHz, CDCl3) d 30.0, 55.7, 63.9, 70.5, 98.8,
114.4, 115.8, 152.5, 153.7, 154.0; IR (KBr) 2953, 2932,
4.3.1.
tert-Butyldimethyl-2-(1-hydroxy-2-propyn)-
phenoxysilane (16). To a stirred solution of tert-butyl-
dimethyl-2-iodophenoxysilane (3.03 g, 9.06 mmol),
PdCl2(PPh3)2 (318 mg, 0.453 mmol), CuI (86 mg,
0.453 mmol) in NEt3 (68 mL) was added propargylic
alcohol (0.60 mL, 9.97 mmol) at rt. After stirring was
continued for 23 h at the same temperature, water (68 mL)
the reaction mixture was diluted with water at the same
temperature, and stirring was continued for 30 min. The
resulting mixture was extracted with Et2O. The combined
extracts were washed with brine, and the residue upon
workup was chromatographed on silica gel with AcOEt–
hexane (15:85 v/v) as eluent to give the propargylic alcohol
16 (2.02 g, 7.69 mmol, 85%) as a colorless oil; RfZ0.50
2897, 2862, 2833, 1674, 1510, 1504, 1456, 1232, 1211 cmK1
;
MS (EI) m/z (relative intensity) 206 [MC, 55], 207 (9), 191
(1), 175 (1), 149 (1), 137 (3), 131 (1), 124 (100), 123 (39),
122 (1), 108 (1), 107 (3), 92 (5), 83 (19), 69 (2), 57 (1);
HRMS (EI) calcd for C12H14O3 [MC] 206.0943. Found
206.0931.
4.2.14. trans-2-(4-Methoxyphenoxymethyl)-3a,4,5,6,7,
7a-hexahydrobenzofuran (11fa). Yield 46%; colorless

4392
M. Yoshida et al. / Tetrahedron 61 (2005) 4381–4393
1
(AcOEt–hexaneZ3:7 v/v); H NMR (400 MHz, C6D6) d
0.26 (s, 6H), 1.16 (s, 9H), 1.93 (br s, 1H), 4.22 (d, JZ
7.3 Hz, 2H), 6.78 (dt, JZ7.3, 1.0 Hz, 1H), 6.83 (dd, JZ7.3,
1.0 Hz, 1H), 7.00–7.04 (m, 1H), 7.51 (dd, JZ7.3, 1.0 Hz,
1H); 13C NMR (100 MHz, C6D6) d K4.1, 18.6, 26.0, 51.7,
83.1, 92.1, 116.1, 120.2, 121.6, 129.8, 133.9, 157.0; IR
(neat) 3329, 2961, 2930, 2897, 2885, 2858, 1487, 1445,
1286, 1258 cmK1; MS (EI) m/z (relative intensity) 262
[MC, 1], 245 (1), 207 (7), 205 (100), 192 (1), 190 (1), 177
(3), 175 (4), 162 (3), 150 (1), 147 (4), 135 (6), 131 (7), 76
(2), 55 (1), 43 (1). Anal. Calcd for C15H22O2Si: C, 68.65; H,
8.45. Found: C, 68.39; H, 8.07.
JZ7.6, 1.0 Hz, 1H), 6.94 (dd, JZ8.3, 1.0 Hz, 1H), 7.25 (dt,
JZ8.3, 1.6 Hz, 1H), 7.32 (dd, JZ7.6, 1.6 Hz, 1H); 13C
NMR (100 MHz, CDCl3) d 20.9, 52.8, 81.1, 90.2, 108.2,
114.9, 120.2, 131.0, 131.8, 157.3, 170.4; IR (KBr) 3408,
2928, 1734, 1726, 1715, 1504, 1452, 1259 cmK1; MS (EI)
m/z (relative intensity) 190 [MC, 70], 191 (10), 189 (1), 147
(26), 146 (2), 131 (100), 130 (35), 105 (1), 92 (1), 85 (1), 76
(3), 43 (15). Anal. Calcd for C11H10O3: C, 69.46; H, 5.30.
Found: C, 69.28; H, 5.38.
4.4. General procedure for the reactions of propargylic
carbonate 1h with nucleophiles. Reaction of 1h with 2a
4.3.2. 2-(1-Methoxylcarbonyloxy-2-propyn)phenol (1h).
To a stirred solution of propargylic alcohol 16 (373 mg,
1.42 mmol) and pyridine (0.46 mL, 5.69 mmol) in CH2Cl2
(8.0 mL) was added dropwise methyl chlorocarbonate
(1.0 mL, 13.0 mmol) at 0 8C, and stirring was continued
for 1 h at the same temperature. The reaction mixture was
diluted with water and extracted with AcOEt. The combined
extracts were washed with aqueous NH4Cl and brine. To a
stirred solution of the residue upon workup in THF (28 mL)
was added TBAF (1.7 mL, 1.70 mmol) at K78 8C, and
stirring was continued for 5 min at the same temperature.
The reaction mixture was quenched with 1.0 M HCl, and
extracted with AcOEt. The combined organic layers were
washed with brine, and the residue upon workup was
chromatographed on silica gel with AcOEt–hexane (30:70
v/v) as eluent to give propargylic carbonate 1h (258 mg,
1.38 mmol, 97% for 2 steps) as colorless needles; RfZ0.18
(AcOEt–hexaneZ2:8 v/v); mp 63–64 8C; 1H NMR
(400 MHz, CDCl3) d 3.85 (s, 3H), 4.98 (s, 2H), 5.94 (s,
1H), 6.86 (t, JZ7.6 Hz, 1H), 6.94 (d, JZ7.3 Hz, 1H), 7.25
(dt, JZ7.3, 1.7 Hz, 1H), 7.32 (dd, JZ7.6, 1.7 Hz, 1H); 13C
NMR (100 MHz, CDCl3) d 55.1, 56.0, 81.9, 89.1, 108.0,
114.9, 120.0, 130.9, 131.8, 155.2, 157.3; IR (KBr) 3445,
1755, 1747, 1738, 1730, 1487, 1447, 1269 cmK1; MS (EI)
m/z (relative intensity) 206 [MC, 58], 207 (8), 205 (1), 175
(1), 147 (5), 131 (47), 130 (100), 105 (1), 101 (4), 93 (1), 92
(1), 89 (4), 76 (6), 75 (5), 59 (3), 43 (1). Anal. Calcd for
C11H10O4: C, 64.07; H, 4.89. Found: C, 63.91; H, 4.88.
To a stirred solution of propargylic carbonate 1h (20.3 mg,
98.5 mmol) in dioxane (1 mL) were added 2-methylcyclo-
hexane-1,3-dione (37.3 mg, 295 mmol), Pd2(dba)3$CHCl3
(5.1 mg, 4.92 mmol) and P(OPri)3 (9.7 mL, 39.4 mmol) in
sealed tube at rt. After stirring was continued for 15 h at
60 8C, the reaction mixture was concentrated and the residue
was chromatographed on silica gel with AcOEt–hexane
(30:70 v/v) as eluent to give the 2-benzofuran 11hj (22 mg,
85.8 mmol, 87%) as a colorless crystals (entry 9 in Table 6).
4.4.1. 2-{(2-Methylcyclohexane-1,3-dionyl)methyl}-
benzofuran (11hj). RfZ0.25 (AcOEt–hexaneZ3:7 v/v);
mp 86–87 8C; H NMR (400 MHz, CDCl3) d 1.37 (s, 3H),
1
1.75–1.98 (m, 2H), 2.55–2.71 (m, 4H), 3.34 (s, 2H), 6.37 (s,
1H), 7.12–7.20 (m, 2H), 7.33 (d, JZ6.8 Hz, 1H), 7.44 (dd,
JZ2.2, 6.8 Hz, 1H); 13C NMR (100 MHz, CDCl3) d 17.2,
23.1, 34.9, 38.4, 63.3, 104.5, 110.7, 110.7, 120.5, 122.6,
123.5, 128.4, 154.2, 209.7; IR (KBr) 2966, 2936, 2876,
1730, 1705, 1697, 1695, 1454, 1254 cmK1; MS (EI) m/z
(relative intensity) 256 [MC, 70], 258 (2), 257 (14), 184 (3),
172 (4), 157 (7), 145 (2), 131 (100), 107 (1), 105 (1), 91 (2),
89 (2), 76 (2). Anal. Calcd for C16H16O3: C, 74.98; H, 6.29.
Found: C, 75.08; H, 6.31.
4.4.2. 2-{(2-Methylcyclopentane-1,3-dionyl)methyl}-
benzofuran (11hk). Yield 87%; colorless needles; RfZ
1
0.30 (AcOEt–hexaneZ3:7 v/v); mp 91–92 8C; H NMR
(400 MHz, CDCl3) d 1.25 (s, 3H), 2.46–2.60 (m, 2H), 2.66–
2.80 (m, 2H), 3.17 (s, 2H), 6.39 (s, 1H), 7.14–7.22 (m, 2H),
7.33 (d, JZ7.8 Hz, 1H), 7.44 (d, JZ7.1 Hz, 1H); 13C NMR
(100 MHz, CDCl3) d 20.6, 34.5, 35.2, 55.5, 104.7, 110.7,
120.7, 122.9, 123.9, 128.2, 153.1, 154.3, 215.6; IR (KBr)
4.3.3. 2-(1-Acetoxy-2-propyn)phenol (1i). To a stirred
solution of propargylic alcohol 30 (118 mg, 450 mmol),
pyridine (73 mL, 899 mmol) in CH2Cl2 (5.0 mL) was added
acetic anhydride (51 mL, 540 mmol) at 0 8C, and stirring was
continued for 2.5 h at the same temperature. To the reaction
mixture was added 10% aq HCl, and the resulting mixture
was extracted with AcOEt. The organic layers were washed
with brine, and the residue upon workup was chromato-
graphed on silica gel with AcOEt–hexane (5:95 v/v) as
eluent to give the acetate (130 mg, 427 mmol, 95%) as a
colorless oil. To the acetate (97 mg, 321 mmol) in THF
(6.5 mL) was added TBAF (0.39 mL, 385 mmol) at K78 8C,
and stirring was continued for 10 min at the same
temperature. The reaction mixture was quenched with
10% aq HCl, and extracted with AcOEt. The combined
extracts were washed with brine, and the residue upon
workup was chromatographed on silica gel with AcOEt–
hexane (20:80 v/v) as eluent to give the phenol 1i (60 mg,
315 mmol, 98%) as colorless needles; RfZ0.18 (AcOEt–
hexaneZ2:8 v/v); mp 74–75 8C; 1H NMR (400 MHz,
CDCl3) d 2.13 (s, 3H), 4.92 (s, 2H), 5.96 (s, 1H), 6.85 (dt,
2972, 2928, 1771, 1732, 1715, 1697, 1456, 1418, 1254 cmK1
;
MS (EI) m/z (relative intensity) 242 [MC, 37], 243 (7), 244
(1), 227 (1), 198 (1), 184 (1), 158 (3), 143 (1), 131 (100),
107 (2), 105 (1), 91 (1), 89 (2), 83 (1), 76 (1), 69 (1), 55 (3);
HRMS (EI) calcd for C15H14O3 [MC] 242.0943. Found
242.0950.
4.4.3. 2-Benzofuranylmethyl methyl malonate (11hl).
Yield 83%; colorless oil; RfZ0.40 (AcOEt–hexaneZ3:7
v/v); H NMR (400 MHz, CDCl3) d 3.45 (s, 2H), 3.73 (s,
1
3H), 5.28 (s, 2H), 6.79 (s, 1H), 7.20–7.33 (m, 2H), 7.47 (d,
JZ8.3 Hz, 1H), 7.56 (d, JZ8.3 Hz, 1H); 13C NMR
(100 MHz, CDCl3) d 41.1, 52.6, 59.5, 107.4, 111.3, 121.3,
122.9, 124.9, 127.7, 151.0, 155.1, 165.9, 166.5; IR (neat)
2955, 1767, 1755, 1747, 1738, 1732, 1454, 1337, 1256,
1146 cmK1; MS (EI) m/z (relative intensity) 248 [MC, 40],
249 (6), 233 (1), 147 (72), 133 (1), 131 (100), 101 (5), 91

M. Yoshida et al. / Tetrahedron 61 (2005) 4381–4393
4393
4. (a) Yoshida, M.; Ihara, M. Angew. Chem., Int. Ed. 2001, 40,
616. (b) Yoshida, M.; Fujita, M.; Ishii, T.; Ihara, M. J. Am.
Chem. Soc. 2003, 125, 4874. (c) Yoshida, M.; Fujita, M.; Ihara,
M. Org. Lett. 2003, 5, 3325. (d) Yoshida, M.; Ihara, M. Chem.
Eur. J. 2004, 2886.
(10), 89 (6), 76 (3), 59 (7), 43 (2); HRMS (EI) calcd for
C13H12O5 [MC] 248.0685. Found 248.0671.
4.5. Procedure for the palladium-catalyzed reaction of
propargylic acetate 1i with 2j
5. A part of the results about our preliminary studies have been
published: Yoshida, M.; Morishita, Y.; Fujita, M.; Ihara, M.
Tetrahedron Lett. 2004, 45, 1861.
To a stirred solution of propargylic acetate 1i (7.5 mg,
39.4 mmol) in dioxane (0.4 mL) were added 2-methyl-
cyclohexane-1,3-dione (15 mg, 118 mmol), Pd2(dba)3$
CHCl3 (2 mg, 2.00 mmol) and dppf (4.4 mg, 7.89 mmol) in
sealed tube at rt. After stirring was continued for 12 h at
60 8C, the reaction mixture was concentrated and the residue
was chromatographed on silica gel with AcOEt–hexane
(30:70 v/v) as eluent to give the 2-benzofuran 11hj (8 mg,
31.2 mmol, 79%), which was identical with the above
compound 11hj in all respects (Scheme 10).
6. Tan, H.; Espenson, J. H. J. Mol. Catal. A 2000, 152, 83.
7. (a) Su, C.-C.; Chen, J.-T.; Lee, G.-H.; Wang, Y. J. Am. Chem.
Soc. 1994, 116, 1938. (b) Ogoshi, S.; Tsutsumi, K.; Kurosawa,
H. J. Organomet. Chem. 1995, 493, C19. (c) Tsutsumi, K.;
Ogoshi, S.; Nishiguchi, S.; Kurosawa, H. J. Am. Chem. Soc.
1998, 120, 1938. (d) Tsutsumi, K.; Kawase, T.; Kakiuchi, K.;
Ogoshi, S.; Okada, Y.; Kurosawa, H. Bull. Chem. Soc. Jpn.
1999, 72, 2687. (e) Ogoshi, S.; Kurosawa, H. J. Synth. Org.
Chem. Jpn 2003, 61, 14.
8. Recently, Mori reported a similar type of palladium-catalyzed
reaction of propargylic carbonates with benzoate leading to
formation of substituted carbapenams, isoquinolines and
benzoazepines; see Ref. 3h,i.
Acknowledgements
This study was supported in part by a Grant-in-Aid for the
Encouragement for Young Scientists (B) from the Japan
Society for the Promotion of Science (JSPS) (for M.Y.).
9. We previously observed the formation of phenoxy substituted
dihydrofuran as a byproduct by the reaction of 4-methoxy-
carbonyloxy-2-butyn-1-ol with phenol, see Ref. 4a,b.
10. It is generally believed that the monodentate ligand is not
suitable for the reactions of propargylic compounds with soft
nucleophiles (see Refs. 2c, 3g and 7d). The observed result
using monodentate PPh3 is therefore interesting in view of this
hypothesis although the precise details of this reaction
mechanism are still unclear.
References and notes
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˚
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