Efficient synthesis of propargylic ethers under the DBU conditions and its application to natural products synthesis

Article abstract of DOI:10.1246/bcsj.80.578

Conversion of dibromides carrying O-functional groups at adjacent positions to the corresponding propargylic ethers was successfully carried out under the DBU conditions through 2-bromo-1-alkenes as intermediates. The optically active γ-lactone-class natural products, such as (-)-muricatacin (4) and (R,R)-sapinofuranone B (5) were synthesized using the propargylic ether intermediate produced by the elimination reaction mentioned above.

Full text of DOI:10.1246/bcsj.80.578

578 Bull. Chem. Soc. Jpn. Vol. 80, No. 3, 578–582 (2007)
ꢀ 2007 The Chemical Society of Japan
Efficient Synthesis of Propargylic Ethers under the DBU Conditions
and Its Application to Natural Products Synthesis
ꢀ
Tadashi Yokoyama, Noriki Kutsumura, Tadaaki Ohgiya, and Shigeru Nishiyama
Department of Chemistry, Faculty of Science and Technology, Keio University,
3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522
Received August 30, 2006; E-mail: nisiyama@chem.keio.ac.jp
Conversion of dibromides carrying O-functional groups at adjacent positions to the corresponding propargylic
ethers was successfully carried out under the DBU conditions through 2-bromo-1-alkenes as intermediates. The optically
active ꢀ-lactone-class natural products, such as (ꢁ)-muricatacin (4) and (R,R)-sapinofuranone B (5) were synthesized
using the propargylic ether intermediate produced by the elimination reaction mentioned above.
In organic synthesis, carbon–carbon bond formation is one
of the most important reactions. Although a number of meth-
Results and Discussion
odologies have been exploited, the critical point is their feasi-
bility towards diverse molecular frameworks, without any
special techniques and limitation of functionalities. Among
functional groups, which enable carbon–carbon bond forma-
tion at desired positions and/or with high chemoselectivity,
alkyne-functions have received much attention for such usage
as, precursors of (Z)- and (E)-1-iodo-1-alkenes,1 2-iodo-1-
alkenes,2 metalated alkenes,1f and alkynes,3 along with sub-
strates of organometal-conducted coupling reactions.4 Gener-
ally, terminal alkyne derivatives have been produced by elim-
ination reactions of 1,1-dibromo-1-alkenes5 and 1,2-dibromo-
alkanes by alkaline metal amides such as LiHMDS and
NaNH2,6 or coupling of aldehydes with phosphonium diazo-
methanes (Scheme 1).7
In closely related investigation, we have developed the
DBU-mediated 2-bromo-1-alkene synthesis from 1,2-dibromo-
alkanes with electron-withdrawing groups at the C-3 posi-
tion, which strengthens the proton-acidity at the C-2 position.8
During studies on the scope and limitation of this elimination
reaction and efforts towards total synthesis of 12-oxygenated-
tremetones,8a tuliparin B,8b and tanikolide,8c,8d we have found
that propargylic ethers were produced as minor products, upon
using excess amounts of DBU. This observation prompted us
to develop a facile propargylic ether synthesis from 1,2-di-
bromoalkanes. Its ready availability might be applicable as
part of multi-step synthesis. We describe herein the elimina-
tion reaction of 2,3-dibromoalkoxy derivatives leading to
propargylic ethers by utilizing DBU as the base, and its appli-
cation towards natural products synthesis.9
To understand the chemistry of the DBU-mediated elimina-
tion of 2,3-dibromoalkoxy derivatives leading to the corre-
sponding propargylic ethers, a variety of substrates and reac-
tion conditions were examined, as can be seen in Table 1
and Fig. 1.
Table 1. Elimination Reactions of the 1,2-Dibromoalkanes
Yields/%
DBU
/mol amt.
Entry
Substrates
Propargylic
ethers
2-Bromo-
1-alkenes
1aÞ
2
1a
1a
1a
1a
1b
1c
1d
1e
1f
1g
1h
1i
1j
1k
1l
2
3
5
7eÞ
5
5
6
5
5
5
5
5
5
5
5
2a (ꢁ)
2a (trace)
2a (92)
2a (10)
2b (42)
2c (68)
2d (92)
2e (71)
2f (95)
2g (ꢁ)
2h (61)
2i (77)
2j (29)
2k (45)
2l (72)
3a (100)
3a (46)
(ꢁ)
3
4bÞ
5
3a (83)
3b (10)
(ꢁ)
6
7
8
(ꢁ)
3e (12)
(ꢁ)
9cÞ
10cÞ
11
12
13
14
15dÞ
3g (94)
(ꢁ)
(ꢁ)
(ꢁ)
3k (30)
(ꢁ)
Reaction conditions, see General procedure in experimental
part. a) 60 ꢂC, 1.5 h. b) 12 h. c) Racemic compound was
used. Relative structure was depicted. d) 23 mmol scale, 85 h.
e) NaOPiv was used.
Br
Br
R2
DBU
Br
R2
R2
3
+
DMF, 80 °C
1
OR1
Scheme 1. The DBU-mediated elimination.
OR1
OR1
Published on the web March 13, 2007; doi:10.1246/bcsj.80.578

T. Yokoyama et al.
Bull. Chem. Soc. Jpn. Vol. 80, No. 3 (2007)
579
Br
O
Br
O
O
Br
R2
R2
R2
R1
R1
R1
3a : R1=NO2, R2=H
3b: R1=Br, R2=H
3e : R1=NO2, R2=n-C5H11
2a : R1=NO2, R2=H
2b: R1=Br, R2=H
2c : R1=OMe, R2=H
2d: R1=OH, R2=H
2e : R1=NO2, R2=n-C5H11
1a : R1=NO2, R2=H
1b: R1=Br, R2=H
1c : R1=OMe, R2=H
1d: R1=OTf, R2=H
1e : R1=NO2, R2=n-C5H11
n-Pr
Br
R1
R2
Br
O
O
O
n-Pr
n-Pr
O2N
O2N
O2N
R
3g
2f
1f : R1=H, R2=Br
1g : R1=Br, R2=H
R
O
O
Br
Br
2h : R=NO2
2i : R=Br
1h : R=NO2
1i : R=Br
O
O
O
O
Br
Br
O2N
F3C
O2N
2j
1j
Br
Br
F3C
F3C
Br
O
O
O
3k
2k
1k
O
O
O
O
Br
Br
OPMB
2l
OPMB
1l
Fig. 1.
Upon using 1a, which provided the corresponding bromo-
olefin 3a by 2 or 3 molar amounts of DBU, 5 molar amounts
of the base provided the alkyne 2a in 92% yield (Entries 1–3).
Dependence of the product yields on the amount of DBU indi-
cated the propargylic ether is produced through the bromo-ole-
fin intermediate. Limitation of NaOPiv as a base was revealed:
NaOPiv (7 molar amounts) provided a 1:8 mixture of 2a and
3a (Entry 4), while the desired bromo-olefins were produced
in high yields by 2 molar amounts of the base.8a The ability
of NaOPiv to remove the sp2 protons might be too low to pro-
vide the corresponding propargylic ethers. From a comparison
of functional groups at the para-positions of the aromatic res-
idue, stronger electron-withdrawing property like that of a
nitro group, provided the propargylic ethers 2 in higher yields
than others (Entries 3, 5, and 6). When a TfO group was used
as a functional group on the aromatic residue, propargylic
ether 2d was produced in high yield (Entry 7): removal of
the sulfonyl ester might take place after the construction of
the triple bond, because the corresponding alkene did not pro-
vide 2d even in the presence of excess DBU. In the presence of
an alkyl chain at the C-3 position (1e), a decrease of the acidity
of protons at C-1 and -2 by an inductive effect of the alkyl
chain, caused a relatively low yield of the elimination reaction,
and alkene 3e was obtained. In the case of internal dibromides,
syn-derivative 1f afforded 2f in 95% yield, whereas bromo-
olefin 3g was obtained from the anti-derivative 1g (Entries 9
and 10): these results strongly suggested that this elimination
might proceed in a two-step trans-elimination manner. In con-
trast to phenyl substituents, the dihydrobenzofuran residue will
be a potent synthetic precursor for several complicated mole-
cules. Similar to the case of 1e with an alkyl function, the di-
hydrobenzofuran residue (1h and 1i) afforded the correspond-
ing propargylic ethers in moderate yields (Entries 11 and 12).
Introduction of an acyloxy function at the C-3 position (1j)
provided 2j in only 29% yield, and no production of the corre-
sponding alkene was monitored. Although the high electron-
withdrawing property of the acyl function would be expected
to contribute the effective abstraction of protons, the preceding
removal of the acyl function interfered with the conversion
process to the corresponding propargylic ethers. In the case

580 Bull. Chem. Soc. Jpn. Vol. 80, No. 3 (2007)
DBU-Mediated Synthesis of Propargylic Ethers
O
O
b
O
O
Br
Br
OR
OPMB
6: R=H
1l
a
O
7: R=PMB
d
e
O
O
O
c
5
4
OH
O
O
2l
OPMB
O
I
f
O
8
OPMB
OR1 R2
9: R1=PMB, R2=I
10: R1=PMB, R2=(E)-CH=CHMe
5: R1=H, R2=(E)-CH=CHMe
g
h
Scheme 2. Reagent and conditions: a. p-methoxybenzyl trichloroacetimidate, TfOH/Et2O (100%). b. Pyr.-HBr3/CH2Cl2 (100%).
c. DBU (5 mol amt.)/DMF, 80 ꢂC (72%). d. i) (E)-1-iododec-1-ene, CuI, PdCl2(Ph3P)2, Et3N; ii) H2, 10% Pd–C, MeOH (97%
in 2 steps). e. NIS, AgNO3/acetone (80%). f. NBSH, Et3N/THF–iPrOH (100%). g. PdCl2(dppf), (E)-prop-1-enyl(dihydroxy-
borane), CsF/PhMe (87%). h. DDQ/CH2Cl2–H2O (89%).
of the benzylic substitution, 1k furnished propargylic ether 2k
in 45% yield, along with the corresponding olefin 3k in 30%
yield, which included a small amount of the 1-bromo isomer.
Apparently, insertion of a methylene lowered the electron-
withdrawing effect of the aromatic residue. Even in the pres-
ence of the ꢀ-lactone moiety (1l), the desired elimination reac-
tion proceeded to give 2l in 72% yield (Entry 15). Different
from esters (Entry 13), the lactone ring may be cyclized, even
when the ester linkage is cleaved under basic conditions.
Therefore, 2l was obtained in better yield than the case of 1j
carrying the benzoyloxy function.
As mentioned above, intermediate 2l was produced by the
DBU-mediated elimination reaction of 1l, which can be syn-
thesized from the corresponding olefin derivative 612 by PMB
protection and bromination (Scheme 2). The Sonogashira cou-
pling of 2l with (E)-1-iododec-1-ene, followed by hydrogenoly-
sis simultaneously to saturate the triple bond and to remove
23
the protecting group, provided 4; the optical rotation ½ꢁꢃD
20
23
20
ꢁ21:0 (c 0.10, CHCl3) (lit. ½ꢁꢃD ꢁ16:1,10 ½ꢁꢃD ꢁ19:5,11b ½ꢁꢃD
ꢁ23:311k) indicated that the synthetic pathway did not affect
the continuous stereochemistry.
Based on the muricatacin-synthesis, we attempted a syn-
thesis of (R,R)-sapinofuranone B (5), a phytotoxin isolated
from Saphaeropsis sapinea.13 Its enantiomeric substance iso-
lated from Acremonium strictum has been synthesized by two
groups.14 Our approach involved conversion of 2l to the corre-
sponding cis-iodovinyl derivative, which was coupled with the
appropriate boronic acid under the Suzuki–Miyaura coupling
conditions.15 Thus, 2l was allowed to react with NIS in the
presence of AgNO3 to give iodide 8 in 80% yield, which was
reduced under the diimide conditions using NBSH (o-nitro-
phenylsulfonylhydrazide)16 quantitatively to give the cis-iodo-
olefin 9. Coupling with (E)-1-prop-1-enyl(dihydroxyborane) in
the presence of PdCl2(dppf) and CsF successfully furnished
the desired product 10 in 87% yield. Finally, deprotection of
the PMB group by DDQ provided 5 in 89% yield. Under the
full range of spectroscopic data, the synthetic sample was
superimposable to the natural (R,R)-sapinofuranone B (5).
In conclusion, despite the heated conditions in the presence
of a slight excess DBU, 2,3-dibromoalkoxy derivatives were
successfully converted to the corresponding propargylic ethers,
through the corresponding alkene intermediates. The effective
The relatively facile elimination methodology leading to
alkyne derivatives, prompted us to demonstrate its application
to natural products synthesis. Along this line, we selected the
ꢀ-lactone-class derivatives as the target molecules.
Synthesis of (À)-Muricatacin (4) and (R,R)-Sapinofura-
none B (5). The title compounds might be synthesized by us-
ing 2l as a common intermediate, and the relatively simple
structure of (ꢁ)-muricatacin (4) would be a synthetic model
for (R,R)-sapinofuranone B (5). (ꢁ)-Muricatacin (4) was iso-
lated from seeds of Annona muricata, and exhibited cytotoxic
activity against certain human tumor cell lines.10 Total synthe-
sis of this molecule, as well as its analogues, has been reported
by several groups.11 In contrast to other groups, our synthetic
strategy using the propargylic ether intermediate, enabled fac-
ile derivatization of the alkyl moiety, to contribute to struc-
ture–activity relationship studies of biological activity. Indeed,
influence of the carbon-chain length of muricatacin on cyto-
toxicity was studied.11 A propargylic ether derivative, like 2l,
might be utilized as a common intermediate to provide muri-
catacin-analogues concerned with the alkyl chain residue.

T. Yokoyama et al.
Bull. Chem. Soc. Jpn. Vol. 80, No. 3 (2007)
581
1780 cmꢁ1
;
1H NMR ꢂ 1.88 (1H, m), 2.34–2.59 (3H, m), 3.72–
elimination reaction required the electron-withdrawing ability
of the O-functional groups at the C-1 position. Application
of this reaction to synthesis of natural molecules, was demon-
strated by the synthesis of (ꢁ)-muricatacin (4) and (R,R)-
sapinofuranone B (5). For the relatively simple and reliable
procedure, this elimination methodology might be included
in reaction candidates applicable to multistep synthesis.
3.94 (5.7H, m), 4.06 (0.3H, dd, J ¼ 3:9, 11.7 Hz), 4.19 (0.7H, m),
4.43 (0.3H, m), 4.69 (1H, m), 4.81–4.94 (1.7H, m), 5.10 (0.3H,
m), 6.90 (2H, d, J ¼ 8:4 Hz), 7.29 (2H, m); 13C NMR ꢂ 24.7, 28.1,
32.5, 50.2, 55.3, 74.2, 78.8, 83.2, 114.0(2), 129.5, 129.9(2), 159.4,
176.1; HRMS m=z 419.9598, calcd. for C15H18Br2O4: Mþ,
419.9572.
(5R)-5-[(1R)-1-(4-Methoxybenzyloxy)prop-2-ynyl]-4,5-dihy-
dro-2(3H)-furanone (2l). A mixture of 1l (9.7 mg, 23 mmol) and
DBU (17 mL, 115 mmol) in DMF (1 mL) was stirred at 80 ꢂC for
85 h. After the addition of 2 M aq HCl and the following work-
up, a crude product was chromatographically purified (hexane/
Experimental
General. IR spectra were recorded on a JASCO Model A-202
1
spectrophotometer. H NMR and 13C NMR spectra were obtained
22
on JEOL JNM EX-270 and JEOL JNM GX-400 spectrometers in a
deuteriochloroform (CDCl3) solution using tetramethylsilane as
an internal standard. High-resolution mass spectra were obtained
on a Hitachi M-80 B GC-MS spectrometer operating at the ioni-
zation energy of 70 eV or on a JEOL JMS-700 (FAB) spectrome-
ter. Optical rotations were recorded at the sodium D line and at
ambient temperatures with a JASCO DIP-360 digital polarimeter.
Preparative and analytical TLC were carried out on silica-gel
plates (Kieselgel 60 F254, E. Merck AG, Germany) using UV light
and/or 5% phosphomolybdic acid in ethanol for detection. Kanto
Chemical silica 60N (spherical, neutral, 63–210 mm) was used
for column chromatography. Silica-gel column chromatography
was used for purification of crude products, unless otherwise stat-
ed. DMF (dimethylformamide) dehydrated grade (Kanto Kagaku
Ltd.) was used for reactions. Work-up procedure, unless otherwise
stated, was performed as follows: a reaction mixture was parti-
tioned between EtOAc or CHCl3 and H2O. The organic layer
was washed with brine, dried (Na2SO4), and then evaporated.
General Procedure of the DBU-Mediated Elimination Reac-
tion: 1-Nitro-4-(prop-2-ynyloxy)benzene (2a). To a solution of
1a (186 mg, 0.5 mmol) in DMF (9.2 mL) was added DBU (381
mg, 2.5 mmol) at 0 ꢂC; the mixture was stirred at 80 ꢂC for 16 h.
The reaction mixture was diluted with a 2:1 mixture of hexane
and EtOAc, washed with 1 M (1 M = 1 mol Lꢁ1) aq HCl, H2O,
and brine. The organic layer was dried (Na2SO4), and concentrat-
ed in vacuo. A crude product was purified by silica-gel column
chromatography to give 2a (89 mg, 92%). The spectroscopic data
was in accordance with commercially available sample.
EtOAc 2/12) to give 2l (4.3 mg, 72%) as a colorless oil: ½ꢁꢃD
1
ꢁ112:5 (c 1.00, CHCl3); IR (film) 3274, 1774 cmꢁ1; H NMR ꢂ
2.24–2.36 (2H, m), 2.44–2.53 (2H, m), 2.65 (1H, m), 3.81 (3H, s),
4.25 (1H, dd, J ¼ 2:8, 4.8 Hz), 4.50 (1H, d, J ¼ 12 Hz), 4.62 (1H,
m), 4.78 (1H, d, J ¼ 12 Hz), 6.89 (2H, d, J ¼ 8:8 Hz), 7.28 (2H,
d, J ¼ 8:8 Hz); 13C NMR ꢂ 23.7, 28.3, 55.6, 69.9, 70.9, 78.7,
79.8, 100.8, 114.2(2), 129.0, 130.1(2), 159.7, 177.0; HRMS m=z
260.1033, calcd. for C15H16O4: Mþ, 260.1049.
(À)-Muricatacin (4). To a mixture of (E)-1-iododec-1-ene
(12 mg, 45 mmol), Et3N (8 mL, 57 mmol), CuI (0.37 mg, 1.9 mmol),
mol), and PdCl2(Ph3P)2 (2.0 mg, 3.9 mmol) was added 2l (10 mg,
38 mmol) in benzene (1.5 mL) were added at 0 ꢂC. After being stir-
red at room temperature for 19 h and the following work-up, a
crude product was chromatographically purified (hexane/EtOAc
2/1) to give a colorless oil. A solution of the product in MeOH
(2 mL) in the presence of catalytic 10% Pd–C was stirred for
26 h under a hydrogen atmosphere. After filtration through a
Celite pad, the solvent was removed. A crude product was chro-
matographically purified (hexane/EtOAc 2/1) to give 4 (10.6 mg,
97% in two steps) as colorless plates (hexane–EtOAc): mp 67 ꢂC;
23
½ꢁꢃD ꢁ21:0 (c 0.10, CHCl3); IR (film) 3445, 2918, 2848, 1741,
1
1465 cmꢁ1; H NMR ꢂ 0.88 (3H, t, J ¼ 6:8 Hz), 1.20–1.40 (20H,
m), 1.53 (2H, m), 1.83 (1H, d, J ¼ 5:9 Hz), 2.07–2.18 (1H, m),
2.21–2.30 (1H, m), 2.57 (1H, dd, J ¼ 17:6, 8.8 Hz), 2.60 (1H,
ddd, J ¼ 17:6, 9.8, 4.9 Hz), 3.56 (1H, m), 4.41 (1H, dt, J ¼ 7:3,
4.9 Hz); 13C NMR ꢂ 14.1, 22.7, 24.1, 25.4, 28.7(2), 29.3(2),
29.46, 29.54, 29.61, 29.64, 31.9, 32.9, 73.7, 82.9, 177.1; HRMS
m=z 284.2349, calcd. for C17H32O3: Mþ, 284.2350.
(5R)-5-[(1R)-1-(4-Methoxybenzyloxy)prop-2-enyl]-4,5-dihy-
To a solution of 612 (506 mg, 3.6
(5R)-5-[(1R)-1-(4-Methoxybenzyloxy)-3-iodoprop-2-ynyl]-4,5-
dihydro-2(3H)-furanone (8).
dro-2(3H)-furanone (7).
A mixture of 2l (50 mg, 0.19
mmol) in Et2O (25 mL) were added dropwise TfOH (1 mL, 10.7
mmol) and PMBOC(NH)CCl3 (5.01 g, 18 mmol) over 30 min at
0 ꢂC. After being stirred for 18 h at room temperature and the fol-
lowing work-up, the reaction mixture was chromatographically
purified (CHCl3/EtOAc 10/1) to give 7 (934 mg, 100%) as a col-
mmol), NIS (55 mg, 0.23 mmol), and AgNO3 (19.5 mg, 0.115
mmol) in acetone (1 mL) was stirred at 0 ꢂC for 1 h. After work-
up, a crude product was chromatographically purified (CHCl3/
24
EtOAc 20/1) to give 8 (59.7 mg, 80%) as a colorless oil: ½ꢁꢃD
1
ꢁ129:3 (c 1.00, CHCl3); IR (film) 1774, 1513 cmꢁ1; H NMR ꢂ
24
orless oil: ½ꢁꢃD ꢁ50:9 (c 1.00, CHCl3); IR (film) 2938, 1776,
2.20–2.35 (2H, m), 2.43–2.66 (2H, m), 3.84 (3H, s), 4.34 (1H, m),
4.48 (1H, m), 4.60 (1H, m), 4.77 (1H, d, J ¼ 11:2 Hz), 6.89 (2H,
d, J ¼ 8:4 Hz), 7.24 (2H, m); 13C NMR ꢂ 23.5, 27.9, 55.3, 70.8,
71.0, 79.7, 80.6, 89.4, 113.8(2), 128.6, 129.8(2), 159.4, 176.6;
HRMS m=z 387.0118, calcd. for C15H16IO4: M þ H, 387.0094.
(5R)-5-[(1R,2Z)-(4-Methoxybenzyloxy)-3-iodoprop-2-enyl]-
4,5-dihydro-2(3H)-furanone (9). To a solution of 8 (11.2 mg,
29 mmol) in THF–iPrOH (1 mL) were added successively NBSH
(31.5 mg, 145 mmol) and Et3N (20 mL, 145 mmol) at 0 ꢂC. After
being stirred for 19 h at room temperature and the following work-
up, a crude product was chromatographically purified (CHCl3/
1513 cmꢁ1 1H NMR ꢂ 2.06 (1H, m), 2.18 (1H, m), 2.43 (1H,
;
m), 2.56 (1H, m), 3.81 (3H, s), 3.84 (1H, m), 4.33 (1H, d, J ¼
11:6 Hz), 4.53 (1H, m), 4.60 (1H, d, J ¼ 11:6 Hz), 5.35–5.42 (2H,
m), 5.83 (1H, m), 6.88 (2H, d, J ¼ 8:4 Hz), 7.24 (2H, d, J ¼ 8:4
Hz); 13C NMR ꢂ 23.8, 28.3, 55.3, 70.0, 80.9, 81.4, 113.7(2), 120.4,
129.3(2), 129.7, 133.6, 159.1, 177.2; HRMS m=z 262.1191, calcd.
for C15H18O4: Mþ, 262.1204.
(5R)-5-[(1S)-2,3-Dibromo-1-(4-methoxybenzyloxy)propyl]-
4,5-dihydro-2(3H)-furanone (1l). A mixture of 7 (934 mg, 3.6
mmol), pyridine (0.37 mL, 4.6 mmol), and Pyr HBr3 (2.28 g,
ꢄ
21
7.1 mmol) in CH2Cl2 (20 mL) was stirred at 0 ꢂC for 12 h. After
the addition of sat. aq Na2S2O3 and the following work-up, a
crude product was chromatographically purified (hexane/EtOAc
5/1) to give 1l (1.50 g, 100%) as a colorless oil: IR (film) 2937,
EtOAc 20/1) to give 9 (11.2 mg, 100%) as a colorless oil: ½ꢁꢃD
þ7:3 (c 1.00, CHCl3); IR (film) 2937, 1776, 1513 cmꢁ1; 1H NMR
ꢂ 2.03–2.27 (2H, m), 2.42 (1H, m), 2.62 (1H, m), 3.79 (3H, s),
4.13 (1H, m), 4.32 (1H, d, J ¼ 12:0 Hz), 4.57 (2H, m), 6.36

582 Bull. Chem. Soc. Jpn. Vol. 80, No. 3 (2007)
DBU-Mediated Synthesis of Propargylic Ethers
(1H, m), 6.65 (1H, d, J ¼ 7:6 Hz), 6.87 (2H, d, J ¼ 8:4 Hz), 7.24
(2H, d, J ¼ 8:4 Hz); 13C NMR ꢂ 23.7, 28.1, 55.1, 70.3, 80.6, 81.5,
86.6, 113.7(2), 129.2, 129.4(2), 137.7, 159.0, 177.0; HRMS m=z
388.0156, calcd. for C15H17IO4: Mþ, 388.0172.
3
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4
a) I. Izzo, S. De Caro, F. De Riccardis, A. Spinella, Tetra-
(5R)-5-[(1R,2Z,4E)-1-(4-Methoxybenzyloxy)hexa-2,4-dienyl]-
4,5-dihydrofuranone (10). To a solution of 9 (18.5 mg, 48 mmol)
in PhMe (3 mL) were added successively CsF (14.5 mg, 96 mmol),
(E)-1-prop-1-enyl(dihydroxyborane) (8.2 mg, 96 mmol) and PdCl2-
(dppf) (3.9 mg, 4.8 mmol) at 0 ꢂC. After being stirred at room tem-
perature for 15 h and the following work-up, the reaction mixture
was chromatographically purified (CHCl3/EtOAc 10/1) to give
hedron Lett. 2000, 41, 3975. b) K. Sonogashira, Y. Tohda, N.
Hagihara, Tetrahedron Lett. 1975, 16, 4467. c) R. E. Ireland, P.
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5
a) E. J. Corey, P. L. Fuchs, Tetrahedron Lett. 1972, 13,
3769. b) C. Mukai, J. S. Kim, H. Sonobe, M. Hanaoka, J. Org.
Chem. 1999, 64, 6822.
6
a) A. Furstner, D. De Souza, L. Parra-Rapado, J. T. Jensen,
¨
22
10 (12.5 mg, 87%) as a colorless oil: ½ꢁꢃD ꢁ48:5 (c 1.00, CHCl3);
Angew. Chem., Int. Ed. 2003, 42, 5358. b) D. Kim, J. Lee, P. J.
Shim, J. I. Lim, T. Doi, S. Kim, J. Org. Chem. 2002, 67, 772.
c) T. Yoshimitsu, K. Ogasawara, J. Chem. Soc., Chem. Commun.
1994, 2197. d) P. F. Keusenkothen, M. B. Smith, J. Chem. Soc.,
Perkin Trans. 1 1994, 2485.
IR (film) 2935, 1776, 1513 cmꢁ1; 1H NMR ꢂ 1.80 (3H, d, J ¼ 6:8
Hz), 2.04 (1H, m), 2.19 (1H, m), 2.43 (1H, m), 2.57 (1H, m), 3.81
(3H, s), 4.30 (1H, m), 4.31 (1H, d, J ¼ 11:2 Hz), 4.53 (1H, m),
4.59 (1H, d, J ¼ 11:7 Hz), 5.26 (1H, m), 5.83 (1H, m), 6.18
(1H, m), 6.31 (1H, t, J ¼ 11:2 Hz), 6.87 (2H, m), 7.24 (2H, m);
13C NMR ꢂ 18.4, 24.1, 28.4, 55.3, 69.6, 75.0, 81.8, 113.7(2),
123.1, 126.0, 129.5(2), 129.9, 133.4, 134.7, 159.1, 177.2; HRMS
m=z 302.1523, calcd. for C18H22O4: Mþ, 302.1517.
7
a) E. Quesada, R. J. K. Taylor, Tetrahedron Lett. 2005, 46,
6473. b) K. Miwa, T. Aoyama, T. Shioiri, Synlett 1994, 107.
a) T. Ohgiya, S. Nishiyama, Chem. Lett. 2004, 33, 1084.
8
b) T. Ohgiya, S. Nishiyama, Heterocycles 2004, 63, 2349.
c) T. Ohgiya, S. Nishiyama, Tetrahedron Lett. 2004, 45, 8273.
d) T. Ohgiya, K. Nakamura, S. Nishiyama, Bull. Chem. Soc.
Jpn. 2005, 78, 1549.
(R,R)-Sapinofuranone B (5). A mixture of 10 (33.7 mg, 0.11
mmol) and DDQ (38.0 mg, 0.17 mmol) in CH2Cl2 (2.2 mL)–H2O
(0.2 mL) was stirred at 0 ꢂC for 2.5 h. After work-up, a crude prod-
uct was chromatographically purified (hexane/EtOAc 2/1) to give
9
Part of this work was reported, see: N. Kutsumura, T.
22
5 (18.1 mg, 89%) as a colorless oil: ½ꢁꢃD ꢁ12:6 (c 0.50, CHCl3)
Yokoyama, T. Ohgiya, S. Nishiyama, Tetrahedron Lett. 2006,
47, 4133.
(optical purity: 90% ee); IR: 3421, 1772 cmꢁ1 1H NMR ꢂ 1.82
;
(3H, dd, J ¼ 0:8, 6.8 Hz), 2.03–2.12 (2H, m), 2.19–2.28 (1H, m),
2.49–2.67 (2H, m), 4.47 (1H, m), 4.58 (1H, m), 5.32 (1H, m), 5.86
(1H, m), 6.20 (1H, t, J ¼ 11:7 Hz), 6.36 (1H, m); 13C NMR ꢂ 18.5,
23.8, 28.5, 70.1, 82.8, 123.8, 125.9, 133.88, 133.94, 176.8; HRMS
m=z 165.0901, calcd. for C10H13O2: M ꢁ OH, 165.09145.
10 M. J. Rieser, J. F. Kozlowski, K. V. Wood, J. L.
McLaughlin, Tetrahedron Lett. 1991, 32, 1137.
11 a) B. Dhotare, A. Chattopadhyay, Tetrahedron Lett. 2005,
´
´
46, 3103. b) M. Carda, S. Rodrıguez, F. Gonzalez, E. Castillo, A.
Villanueva, J. A. Marco, Eur. J. Org. Chem. 2002, 2649. c) M.
Chandrasekhar, K. L. Chandra, V. K. Singh, Tetrahedron Lett.
2002, 43, 2773. d) V. Popsavin, S. Grabez, M. Popsavin, J.
Petrovic, Carbohydr. Lett. 2000, 3, 411. e) M. Szlosek, X. Franck,
This work was supported by a Grant-in-Aid for the 21st
Century COE program ‘‘Keio Life Conjugate Chemistry,’’ as
well as Scientific Research C from the Ministry of Education,
Culture, Sports, Science and Technology, Japan.
`
B. Figadere, A. Cave, J. Org. Chem. 1998, 63, 5169. f) S.-H.
Yoon, H.-S. Moon, S.-K. Kang, Bull. Korean Chem. Soc. 1998,
´
´
19, 1016. g) A. Cave, C. Chaboche, B. Figadere, J. C. Harmange,
A. Laurens, J. F. Peyrat, M. Pichon, M. Szlosek, J. Cotte-Lafitte,
`
Supporting Information
´
A. M. Quero, Eur. J. Med. Chem. 1997, 32, 617. h) A. Gypser,
Preparation of 1a and 1c–1k. Spectroscopic data of 2e, 2f, 2h,
2i, 2k, 3a, 3e, 3g, and 3k. This material is available free of charge
on the web at: http://www.csj.jp/journals/bcsj/.
M. Peterek, H.-D. Scharf, J. Chem. Soc., Perkin Trans. 1 1997,
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