First total synthesis of (+)-indicanone

Article abstract of DOI:10.1039/c2ob25500f

The first total synthesis of the guaiane-type sesquiterpene, (+)-indicanone (1), isolated from the root of Wikstroemia indica, was accomplished based on the rhodium(i)-catalyzed Pauson-Khand-type reaction of the allenyne derivative, which was derived from

Full text of DOI:10.1039/c2ob25500f

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PAPER
First total synthesis of (+)-indicanone†
Yujiro Hayashi, Kumiko Ogawa, Fuyuhiko Inagaki and Chisato Mukai*
Received 8th March 2012, Accepted 25th April 2012
DOI: 10.1039/c2ob25500f
The first total synthesis of the guaiane-type sesquiterpene, (+)-indicanone (1), isolated from the root of
Wikstroemia indica, was accomplished based on the rhodium(I)-catalyzed Pauson–Khand-type reaction of
the allenyne derivative, which was derived from (+)-limonene. This total synthesis unambiguously
confirmed the complete structure of (+)-indicanone involving its absolute stereochemistry.
some chemical modification, lead to the formation of the target
Introduction
natural product (+)-1 with the (R)-configuration.
In 2005, Kitanaka1 reported the isolation of a new guaiane-type
sesquiterpene, (+)-indicanone (1), along with two known bifla-
vonoids, sikokianin B and sikokianin C, from the root of
Wikstroemia indica (Thymelaeceae), which is distributed in the
southeast China. Wikstroemia indica has long been used as a tra-
ditional crude drug for the treatment of pneumonia, rheumatism,
and bronchitis in China. (+)-Indicanone (1) was shown to inhibit
not only nitric oxide production with a stronger IC50 at 9.3 μM
than that of quercetine (IC50 at 24.8 μM),2,3 but also the induci-
ble nitric oxide synthase gene expression. The structure of this
anti-inflammatory guaiane-type sesquiterpene 1, except for its
absolute configuration,4 was elucidated by the spectral evidence,
Treatment of the vinyl phosphate derivative 27 with LDA8
unexpectedly produced an intractable mixture. After screening
several bases, nBuLi and sBuLi were found to produce the
alkyne derivative 6, but the yields were rather low, presumably
s
due to its volatility. Thus, compound 2 was exposed to BuLi in
THF at −78 °C to room temperature and the resulting acetylide
was consecutively treated with paraformaldehyde providing the
desired propargyl alcohol derivative 7 in 73% yield. Protection
of the primary alcohol and deacetalization of 7 was achieved by
p-methoxybenzylation and acid treatment under the standard
conditions to afford the aldehyde 8 in 84% yield. The Ohira–
Bestmann reagent9 effected the transformation of the aldehyde
moiety of 8 into a triple bond to furnish 9 in quantitative yield,
which was subsequently treated with LHMDS and methyl iodide
to give the internal alkyne derivative 10 in quantitative yield.
Removal of p-methoxybenzyl group of 10 by DDQ easily pro-
ceeded to produce the propargyl alcohol derivative 11, a precur-
sor for the allene formation, in 92% yield. Compound 11 was
then treated with choromethyl formate to furnish the carbonate
12 in quantitative yield. Upon exposure to Tsuji’s conditions10
1
in particular, based on the careful examination of the H NMR
spectra. Recent efforts from our laboratory disclosed that the
[RhCl(CO)dppp]2-catalyzed
Pauson–Khand-type
reaction
(PKTR) of the allenynes5,6 consistently produced the corre-
sponding bicyclo[5.3.0]decadienone skeletons in satisfactory
yields. Described herein is the first total synthesis of (+)-1 start-
ing from (+)-limonene by taking advantage of the [RhCl(CO)-
dppp]2-catalyzed PKTR of allenynes5 for the construction of the
core carbon framework of 1.
The simple retrosynthesis of (+)-1 afforded the reasonable
tactics described in Scheme 1. The vinyl phosphate moiety of
the known diene 2,7 derived from (+)-limonene, would be con-
verted into the propargyl alcohol derivative 3, which should be a
precursor of the allenyl functional group in the latter stage. The
acetal group of 3 would be transformed into the propyne deriva-
tive 4 by a conventional procedure. Finally, the rhodium(I)-cata-
lyzed Pauson–Khand-type reaction of allenyne 5 would, after
Division of Pharmaceutical Sciences, Graduate School of Natural
Science and Technology, Kanazawa University, Kakuma-machi,
Kanazawa, 920-1192, Japan. E-mail: mukai@p.kanazawa-u.ac.jp;
Fax: +81-76-234-4410; Tel: +81-76-234-4411
†Electronic supplementary information (ESI) available. See DOI:
10.1039/c2ob25500f
Scheme 1 Retrosynthetic analysis of (+)-indicanone from (+)-limonene.
Org. Biomol. Chem., 2012, 10, 4747–4751 | 4747
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Scheme 3 Synthesis of bicyclo[5.3.0]decadienone 14.
Scheme 2 Synthesis of allenyne derivative 13.
(5 mol% Pd(OAc)2, 25 mol% PPh3 in MeOH under 10 atm CO
pressure), 12 underwent migration to provide the corresponding
allenyl ester 13 with the required all carbon units of 1 in 71%
yield (Scheme 2).
With the allene–alkyne detivative 13 in hand, we investigated
its rhodium(I)-catalyzed PKTR.5 There are two types of products
would be possible from the PKTR of 13 judging from the pre-
vious results.5,11 One is the desired bicyclo[5.3.0] product 145
via the PKTR between the allene and alkyne moieties and the
other is the bicyclo[4.3.0] compound 1511 via the reaction of
the allene group with the alkene moiety. However, the fact that
the PKTR of the allene with the 1,1-disubstituted alkene11 tends
to require a higher CO pressure (e.g. 5 atm) than the reaction
with the alkyne (usually 1 atm) suggested the preferential for-
mation of 14 over 15. As a result, a solution of 13 in toluene was
refluxed in the presence of 5 mol% [RhCl(CO)dppp]2 for 1 h to
provide the bicyclo[5.3.0]decadienone framework 14 in 70%
yield as the main product along with a small amount of the
bicyclo[4.3.0]nonenone skeleton 15 (obtained as a mixture
of diastereoisomers),12 which must have been formed via the
[2 + 2 + 1]-type ring closure between the distal double bond of
the allene functionality and isopropenyl group,11 followed by
migration of a double bond. The bicyclo[5.3.0]decadienone fra-
mework 14 was obtained in an acceptable yield, but we could
not suppress the by-production of 15 despite several changes in
the reaction conditions. In addition, the chemoselective reduction
of the α,β-unsaturated ester group of bicyclo[5.3.0]decadienone
derivative 14 in the presence of the α,β-unsaturated ketone
moiety was not an easy task. Therefore, prior to the Pauson–
Khand-type reaction, the methyl ester group of 13 was reduced
with DIBAL-H to afford 16 in 85% yield (Scheme 3).
Scheme 4 Completion of total synthesis of (+)-indicanone.
(+)-indicanone (1) in a poor yield (8%) together with some
amounts of the α,β-unsaturated aldehyde 17.13 Changing the
rhodium(I) catalyst to [RhCl(CO)2]2 as well as increasing the
loading amount of the catalyst (15 mol%) improved the yield of
1 (37%), but 17 was still consistently formed in some amounts.
The production of 17 is obviously attributed to the unprotected
allenyl alcohol of 16. Therefore, the allenyl alcohol of 16 was
protected by a silyl group to produce 18 in 91% yield, which
was subsequently treated with 5 mol% [RhCl(CO)dppp]2 in
refluxing toluene under 1 atm CO atmosphere to give 19 in 37%
yield. This ring-closing reaction was monitored by TLC indicat-
ing the efficient formation of 19 in the reaction vessel. We tenta-
tively thought that the decomposition of 19 during workup and/
or purification processes occurred which must be a major reason
for its low isolation yield. Thus, after the PKTR of 18, the result-
ing 19 without isolation was subsequently desilylated with
aqueous HCl leading to the highly efficient production of
(+)-indicanone (1){[α]2D1 +16.6° (lit. [α]D23 +14.3°)}14,15 in 95%
yield (Scheme 4).
In summary, we have efficiently completed the first total syn-
thesis of (+)-indicanone (1) from the known phosphate (2)
through 10 steps in a 29% overall yield. This total synthesis
unambiguously established the absolute configuration of the
natural (+)-indicanone to be (R) as indicated in Scheme 1.
The PKTR of 16 was the next subject. The exposure of 16 to
5 mol% [RhCl(CO)dppp]2 as described in Scheme 4 furnished
4748 | Org. Biomol. Chem., 2012, 10, 4747–4751
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(DART) m/z 301 (M+ + 1, 30.3); HRMS (DART) calcd for
C19H25O3 301.1804, found 301.1810.
Experimental
General
IR spectra were measured in CHCl3. 1H NMR spectra were taken
in CDCl3 unless otherwise stated. Tetramethylsilane (0.00 ppm)
for compounds without a silyl group was used as internal stan-
dard unless otherwise stated. 13C NMR spectra were recorded in
CDCl3 with CDCl3 (77.00 ppm) as an internal standard unless
otherwise stated. All reactions were carried out under a nitrogen
atmosphere. Silica gel (silica gel 60, 230–400 mesh) was used
for chromatography. Organic extracts were dried over anhydrous
Na2SO4.
(+)-(R)-4-Isopropenyl-8-(4-methoxybenzyloxy)-1,7-nonadiyne (9)
To a solution of (+)-8 (894 mg, 2.97 mmol) in MeOH (30 mL)
were added Ohira–Bestmann reagent (690 mg, 3.6 mmol) and
K2CO3 (1.2 g, 8.9 mmol) at room temperature. The reaction
mixture was stirred for 1 h at the same temperature. Then the
reaction was quenched by addition of 10% aqueous HCl, and the
mixture was extracted with AcOEt. The extract was washed with
water and brine, dried, and concentrated to dryness. Chromato-
graphy of the residue with hexane–AcOEt (12 : 1) afforded (+)-9
(877 mg, quant.) as a colorless oil; [α]2D7 +24.4 (c 0.64, CHCl3);
1
IR 3307 cm−1; H NMR δ 7.30–7.26 (m, 2H), 6.91–6.86 (m,
(+)-(R)-8,8-Dimethoxy-6-isopropenyl-2-octyn-1-ol (7)
2H), 4.88–4.86 (m, 1H), 4.84–4.80 (m, 1H), 4.52 (s, 2H), 4.12
(t, 2H, J = 2.1 Hz), 3.81 (s, 3H), 2.47–2.39 (m, 1H), 2.29–2.26
(m, 2H), 2.25–2.11 (m, 2H), 1.98 (t, 1H, J = 2.7 Hz), 1.84–1.76
(m, 1H), 1.67 (s, 3H), 1.65–1.57 (m, 1H); 13C NMR δ 159.3,
145.1, 129.73, 129.66, 113.8, 112.8, 86.4, 82.6, 76.3, 71.0, 69.4,
57.3, 55.2, 45.0, 31.0, 23.2, 18.7, 16.7; MS (DART) m/z 297
(M+ + 1, 5.4); HRMS (DART) calcd for C20H25O2 297.1855,
found 297.1848.
To a solution of (+)-27 (1.35 g, 3.86 mmol) in THF (38 mL) was
added s-BuLi (1.0 M in hexane, 8.9 mL, 8.9 mmol) at −78 °C.
The reaction mixture was stirred for 1 h at the same temperature.
Then paraformaldehyde (365 mg) was added to the reaction
mixture, which was stirred for an additional 1 h at room tempera-
ture. The reaction was quenched by addition of saturated
aqueous NH4Cl, and the mixture was extracted with AcOEt. The
extract was washed with water, brine, dried, and concentrated to
dryness. Chromatography of the residue with hexane–AcOEt
(3 : 1) afforded (+)-7 (635 mg, 73%) as a colorless oil; [α]D28
(+)-(R)-6-Isopropenyl-1-(4-methoxybenzyloxy)-2,8-decadiyne (10)
1
+30.4 (c 1.0, CHCl3); IR 3609, 3441 cm−1; H NMR δ 4.80
To a solution of (+)-9 (311 mg, 1.05 mmol) in THF (7.0 mL)
was added LHMDS (0.5 M in THF, 2.4 mL, 1.2 mmol) at
−78 °C. The reaction mixture was stirred for 1 h at the same
temperature. Then MeI (0.40 mL, 5.3 mmol) was added to the
reaction mixture, which was stirred for an additional 3 h at the
same temperature. The reaction was quenched by addition of
saturated aqueous NH4Cl, and the mixture was extracted with
AcOEt. The extract was washed with water and brine, dried, and
concentrated to dryness. Chromatography of the residue with
hexane–AcOEt (20 : 1) afforded (+)-10 (325 mg, quant.) as a
(brs, 1H), 4.76 (brs, 1H), 4.31 (dd, 1H, J = 7.1, 4.4 Hz), 4.27 (s,
2H), 3.30 (s, 3H), 3.28 (s, 3H), 2.34–2.27 (m, 1H) 2.19–2.01
(m, 3H), 1.60 (s, 3H), 1.68–1.51 (m, 4H); 13C NMR δ 145.5,
113.0, 102.9, 86.0, 78.6, 53.1, 52.4, 51.2, 42.2, 35.9, 32.0, 17.8,
16.6; MS (DART) m/z 227 (M+ + 1, 2.6); HRMS (DART) calcd
for C13H23O3 227.1647, found 227.1655.
(+)-(R)-3-Isopropenyl-8-(4-methoxybenzyloxy)-6-octynal (8)
To a solution of (+)-7 (53 mg, 0.23 mmol) in DMF (2.5 mL)
was added 60% NaH in oil (28 mg, 0.70 mmol) at 0 °C. The
reaction mixture was stirred for 1 h at the same temperature.
Then PMBCl (0.060 mL, 0.47 mmol) was added to the reaction
mixture, which was stirred for an additional 1 h at room tempera-
ture. The reaction was quenched by addition of saturated
aqueous NH4Cl, and the mixture was extracted with AcOEt. The
extract was washed with water and brine, dried, and concentrated
to give the crude acetal. To a solution of the crude acetal in
acetone (3 mL) was added 35% aqueous HCl (0.2 mL) at 0 °C.
The reaction mixture was stirred for 1 h at room temperature.
The reaction was quenched by addition of saturated aqueous
NaHCO3, and the mixture was extracted with AcOEt. The
extract was washed with water and brine, dried, and concentrated
to dryness. Chromatography of the residue with hexane–AcOEt
(3 : 1) afforded (+)-8 (59 mg, 84%) as a colorless oil; [α]D28
1
colorless oil; [α]2D6 +20.7 (c 1.5, CHCl3); H NMR δ 7.30–7.28
(m, 2H), 6.90–6.86 (m, 2H), 4.85–4.83 (m, 1H), 4.79–4.76 (m,
1H), 4.52 (s, 2H), 4.12 (t, 2H, J = 2.1 Hz), 3.81 (s, 3H),
2.38–2.31 (m, 1H), 2.28–2.10 (m, 4H), 1.85–1.79 (m, 1H), 1.77
(t, 3H, J = 2.5 Hz), 1.66 (s, 3H), 1.63–1.54 (m, 1H); 13C NMR
δ 159.3, 145.8, 129.75, 129.68, 113.8, 112.3, 86.7, 77.2, 76.7,
76.1, 70.9, 57.3, 55.3, 45.5, 31.0, 23.6, 18.9, 16.7, 3.5; MS
(DART) m/z 311 (M+ + 1, 5.6); HRMS (DART) calcd for
C21H27O2 311.2011, found 311.2001.
(+)-(R)-6-Isopropenyl-2,8-decadiyn-1-ol (11)
To a solution of (+)-10 (757 mg, 2.44 mmol) in CH2Cl2 (12 mL)
and H2O (0.6 mL) was added DDQ (830 mg, 3.66 mmol) at
room temperature. The reaction mixture was stirred for 1 h at the
same temperature. Then the reaction was quenched by addition
of saturated aqueous NaHCO3, and the mixture was extracted
with CH2Cl2. The extract was washed with water and brine,
dried, and concentrated to dryness. Chromatography of the
residue with hexane–AcOEt (8 : 1) afforded (+)-11 (527 mg,
92%) as a colorless oil; [α]2D8 +34.85 (c 1.4, CHCl3); IR 3609,
1
+22.6 (c 0.56, CHCl3); IR 1722 cm−1; H NMR δ 9.67 (t, 1H,
J = 2.3 Hz), 7.29–7.26 (m, 2H), 6.89–6.86 (m, 2H), 4.88–4.84
(m, 1H), 4.84–4.82 (m, 1H), 4.51 (s, 2H), 4.11 (t, 2H, J = 1.8
Hz), 3.80 (s, 3H), 2.83 (quin, 1H, J = 7.3 Hz), 2.52–2.38 (m,
2H), 2.28–2.12 (m, 2H) 1.66 (s, 3H), 1.65–1.60 (m, 2H);
13C NMR δ 201.8, 159.3, 144.6, 129.7, 129.6, 113.8, 113.3,
86.0, 76.5, 71.0, 57.3, 55.2, 47.1, 40.5, 31.8, 18.6, 16.5; MS
1
3447 cm−1; H NMR δ 4.85–4.82 (m, 1H), 4.78–4.76 (m, 1H),
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4.25 (s, 2H), 2.35–2.20 (m, 1H), 2.26–2.07 (m, 4H), 1.83–1.74
(m, 1H), 1.78 (t, 3H, J = 2.5 Hz), 1.65 (s, 3H), 1.62–1.52
(m, 2H); 13C NMR δ 145.7, 112.4, 86.2, 78.4, 77.3, 76.8, 51.4,
45.5, 30.9, 23.6, 18.9, 16.7, 3.5; MS (DART) m/z 191 (M+ + 1,
79.9); HRMS (DART) calcd for C13H19O 191.1436, found
191.1424.
J = 3.0 Hz), 2.28–2.22 (m, 1H), 2.20–2.15 (m, 2H), 2.02–1.83
(m, 2H), 1.77 (t, 3H, J = 2.3 Hz), 1.75–1.66 (m, 1H), 1.64
(s, 3H), 1.55–1.45 (m, 2H); 13C NMR δ 204.2, 146.4, 112.0,
104.5, 78.8, 77.6, 76.5, 62.9, 46.0, 29.7, 26.3, 23.8, 18.8, 3.5;
MS (DART) m/z 205 (M+ + 1, 8.3); HRMS (DART) calcd for
C14H21O 205.1592, found 205.1589.
(+)-(R)-6-Isopropenyl-1-methoxycarbonyloxy-2,8-decadiyne (12)
(+)-(R)-3-(tert-Butyldimethylsilyloxy)-6-isopropenyl-1,2-
To a solution of (+)-11 (411 mg, 2.16 mmol) in CH2Cl2 (10 mL)
were added pyridine (1.0 mL, 13 mmol) and ClCO2Me
(0.50 mL, 6.5 mmol) at 0 °C. The reaction mixture was stirred
for 15 min at the same temperature. Then the reaction was
quenched by addition of saturated aqueous NaHCO3, and the
mixture was extracted with CH2Cl2. The extract was washed
with water and brine, dried, and concentrated to dryness. Chrom-
atography of the residue with hexane–AcOEt (20 : 1) afforded
(+)-12 (536 mg, quant.) as a colorless oil; [α]2D7 +27.6 (c 0.10,
decadien-8-yne (18)
To a solution of (+)-16 (120 mg, 0.590 mmol) in CH2Cl2 (6 mL)
were added TBSCl (134 mg, 0.886 mmol) and Et3N (0.25 mL,
1.8 mmol) and DMAP (3.6 mg, 0.030 mmol) at 0 °C. The reac-
tion mixture was stirred for 13 h at room temperature. Then the
reaction was quenched by addition of water, and the mixture was
extracted with CH2Cl2. The extract was washed with water and
brine, dried, and concentrated to dryness. Chromatography of the
residue with hexane afforded (+)-18 (170 mg, 91%) as a color-
CHCl3); IR 1751 cm−1 1H NMR δ 4.85–4.82 (m, 1H),
;
less oil; [α]D22 +2.7 (c 1.0, CHCl3); IR 1958 cm−1 1H NMR
;
4.78–4.76 (m, 1H), 4.72 (t, 2H, J = 2.3 Hz), 3.80 (s, 3H),
2.33–2.22 (m, 1H), 2.21–2.06 (m, 4H), 1.77 (t, 3H, J = 2.5 Hz),
1.82–1.74 (m, 1H), 1.64 (s, 3H), 1.61–1.51 (m, 1H);
13C NMR δ 155.3, 145.6, 112.4, 88.1, 77.2, 76.8, 73.5, 56.2,
55.0, 45.5, 30.7, 23.6, 18.9, 16.7, 3.5; MS (DART) m/z 249 (M+
+ 1, 10.2); HRMS (DART) calcd for C15H21O3 249.1491, found
249.1484.
δ 4.80–4.79 (m, 1H), 4.75–4.72 (m, 3H), 4.12 (t, 2H, J = 2.3
Hz), 2.28–2.22 (m, 1H), 2.20–2.17 (m, 2H), 2.02–1.92 (m, 1H),
1.91–1.83 (m, 1H), 1.77 (t, 3H, J = 2.5 Hz), 1.72–1.66 (m, 1H),
1.64 (s, 3H), 1.54–1.42 (m, 1H), 0.89 (s, 9H), 0.06 (s, 6H);
13C NMR δ 205.7, 146.9, 112.2, 103.8, 78.1, 76.74, 76.70, 64.6,
46.5, 30.1, 26.4, 26.2, 24.1, 19.1, 18.7, 3.8, −5.0; MS (DART)
m/z 319 (M+ + 1, 10.5); HRMS (DART) calcd for C20H35OSi
319.2457, found 319.2473.
(+)-(R)-6-Isopropenyl-3-methoxycarbonyl-1,2-decadien-8-yne (13)
To a solution of (+)-12 (57.4 mg, 0.231 mmol) in MeOH
(1.0 mL) were added Pd(OAc)2 (2.6 mg, 0.012 mmol) and PPh3
(12 mg, 0.046 mmol) at room temperature. The reaction mixture
was warmed to 40 °C under CO (10 atm) and stirred for 24 h.
Then MeOH was evaporated off, and the residue was chromato-
graphed with hexane–AcOEt (80 : 1) to afford (+)-13 (38 mg,
71%) as a colorless oil; [α]2D3 +7.0 (c 1.6, CHCl3); IR 1965,
(+)-Indicanone (1)
To a solution of (+)-18 (14.7 mg, 0.0462 mmol) in toluene
(1.0 mL) was added [RhCl(CO)dppp]2 (3.0 mg, 2.6 × 10−3
mmol) at room temperature, and reaction mixture was warmed to
refluxed under CO (1 atm) and stirred for 3 h. Then 10%
aqueous HCl (0.5 mL) and MeOH (1 mL) was added to the reac-
tion mixture, which was stirred for an additional 1 h at room
temperature. The reaction was quenched by addition of saturated
aqueous NaHCO3, and the mixture was extracted with AcOEt.
The extract was washed with water and brine, dried, and concen-
trated to dryness. Chromatography of the residue with hexane–
AcOEt (1 : 1) afforded (+)-indicanone (1) (10.2 mg, 95%) as a
colorless oil; [α]2D3 +16.6 (c 0.73, MeOH); IR 3607, 3420,
1936, 1713 cm−1 1H NMR δ 5.14 (t, 2H, J = 3.2 Hz),
;
4.83–4.79 (m, 1H), 4.75 (brs, 1H), 3.74 (s, 3H), 2.27–2.16
(m, 4H), 2.15–2.07 (m, 1H), 1.76 (t, 3H, J = 2.3 Hz), 1.72–1.63
(m, 1H), 1.65 (s, 3H), 1.55–1.46 (m, 1H); 13C NMR
δ 213.8, 167.6, 146.2, 112.2, 100.0, 79.1, 77.6, 76.5, 52.2,
46.0, 30.3, 25.8, 23.8, 18.8, 3.5; MS (DART) m/z 233 (M+ + 1,
100); HRMS (DART) calcd for C15H21O2 233.1542, found
233.1559.
1
1682 cm−1; H NMR δ 4.74 (s, 2H), 4.20 (s, 2H), 2.99 (s, 2H),
2.82 (dd, 1H, J = 15.5, 4.1 Hz), 2.73 (dd, 1H, J = 15.3, 8.9 Hz),
2.64 (ddd, 1H, J = 15.5, 8.4, 2.8 Hz), 2.55–2.44 (m, 2H),
2.05–1.97 (m, 2H), 1.80 (s, 3H), 1.84–1.77 (m, 1H), 1.77 (s,
3H); 1H NMR (acetone-d6) δ 4.74 (br s, 1H), 4.69 (quin, 1H, J =
1.3 Hz), 4.11, 4.08 (ABq, 2H, JAB = 12.7 Hz), 2.95, 2.91 (ABq,
2H, JAB = 20.6 Hz), 2.83 (dd, 1H, J = 15.4, 4.4 Hz), 2.77
(dd, 1H, J = 15.4, 8.5 Hz), 2.63 (ddd, 1H, J = 16.7, 8.5, 2.7 Hz),
2.54–2.45 (m, 2H), 1.99–1.94 (m, 1H), 1.78–1.71 (m, 4H), 1.70
(s, 3H); 13C NMR δ 204.3, 167.1, 149.3, 140.2, 137.6, 133.9,
109.7, 65.7, 43.0, 39.0, 33.5, 32.4, 28.7, 20.5, 8.5; 13C NMR
(acetone-d6) δ 203.5, 167.1, 150.6, 139.8, 139.5, 133.4, 109.7,
65.2, 43.9, 39.2, 33.9, 33.2, 28.9, 20.5, 8.3; MS (DART) m/z
233 (M+ + 1, 100); HRMS (DART) calcd for C15H21O2
233.1542, found 233.1526.
(+)-(R)-6-Isopropenyl-3-hydroxymethyl-1,2-decadien-8-yne (16)
To a solution of (+)-13 (116 mg, 0.500 mmol) in toluene
(5.0 mL) was added DIBAL-H (1.0 M in toluene, 1.5 mL,
1.5 mmol) at −78 °C. The reaction mixture was stirred for 4 h at
the same temperature. Then the reaction was quenched by
addition of MeOH and saturated sodium potassium tartrate
(Rochelle’s salt), and the mixture was extracted with AcOEt. The
extract was washed with water and brine, dried, and concentrated
to dryness. Chromatography of the residue with hexane–AcOEt
(10 : 1) afforded (+)-16 (87 mg, 85%) as a colorless oil; [α]D26
+7.9 (c 0.52, CHCl3); IR 3605, 3450, 1958 cm−1 1H NMR
;
δ 4.90–4.87 (m, 2H), 4.80 (brs, 1H), 4.74 (brs, 1H), 4.04 (t, 2H,
4750 | Org. Biomol. Chem., 2012, 10, 4747–4751
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Acknowledgements
This work was supported in part by a Grant-in Aid for Scientific
Research from the Ministry of Education, Culture, Sports,
Science and Technology, Japan, for which we are thankful.
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Notes and references
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12 A full characterization of this mixture was not done.
13 A full characterization of 17 could not be done due to its instability.
14 The spectral data of the synthetic (+)-1 were identical to those of the
natural one reported in ref. 1 except for two vinylic protons in their 1H
NMR data. In fact, the 1H NMR of the synthetic (+)-1 in CDCl3 showed
two vinylic protons at δ 4.74 as a singlet, while those of the natural product
appeared at δ 4.71 and 4.63 as both singlet in CDCl3 (ref. 1). Professor
Kitanaka kindly provided the 1H NMR spectrum of the natural (+)-1 in
acetone-d6, which was completely superimposed over that of the synthetic
one in acetone-d6. The 1H NMR data in ref. 1 must be the one measured in
acetone-d6 (a personal communication from Professor Kitanaka). Thus, we
concluded that the structure of the natural (+)-indicanoneis unambiguously
proved to be the one described in Scheme 1 by this synthesis.
15 We are indebted to Professor S. Kitanaka, College of Pharmacy, Nihon
University, for generously supplying the 1H NMR spectrum of the natural
(+)-indicanone in acetone-d6.
4 No description regarding the absolute stereochemistry of (+)-1 could be
available from ref. 1.
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6 For the related [RhCl(CO)2]2-catalyzed PKTR of enzymes leading to the
bicyclo[5.3.0] frameworks, see: (a) K. M. Brummond, H. Chen,
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