Total synthesis of (+)-dodoneine and its 6-epimer

Article abstract of DOI:10.1055/s-0029-1216953

The total synthesis of dodoneine and its 6-epimer is described, using HKR of epoxide and reduction with SmI2 reactions as key steps, respectively.

Full text of DOI:10.1055/s-0029-1216953

PAPER
3285
Total Synthesis of (+)-Dodoneine and Its 6-Epimer
Total
S
ynthesis of
o
(+)-Dodonei
w
ne and
I
ts 6-Epim
e
r
r
avaram Sabitha,* Vangala Bhaskar, S. Siva Sankara Reddy, Jhillu S. Yadav
Organic Division I, Indian Institute of Chemical Technology, Hyderabad 500007, India
Fax +91(40)27160512; E-mail: gowravaramsr@yahoo.com
Received 20 March 2009; revised 4 June 2009
Horner–Wadsworth–Emmons reaction was utilized. Epi-
dodoneine (2) could be prepared by SmI2 reduction of
alkoxy keto compound 9, followed by construction of lac-
tone moiety through RCM leading to the target molecule
(Scheme 1).
Abstract: The total synthesis of dodoneine and its 6-epimer is
described, using HKR of epoxide and reduction with SmI2 reactions
as key steps, respectively.
Key words: dodoneine, epidodoneine, trimethylsulfonium iodide,
HKR, SmI2, RCM
The synthesis began with the known alcohol 7 prepared
from MOM protected p-iodophenol 10 and the chiral acet-
ylenic alcohol 11 by Cossford protocol followed by some
functional group manipulations as described in our earlier
communication.4d Oxidation of alcohol 7 using IBX yield-
ed the corresponding aldehyde and subsequently treat-
ment with trimethylsulfonium iodide5 in the presence of
NaH in DMSO–THF affords the corresponding racemic
epoxide in 60% yield (Scheme 2).
Dodoneine (1), a dihydropyranone was isolated from a
parasitic plant Tapinanthus dodoneifolius, which is wide-
ly spread in the Sahelian region (West Africa).1 T. dodo-
neifolius is used as a remedy to treat cholera, diarrhea,
stomachache, wounds, and nervous confusion. It is also
used for cardiovascular and respiratory diseases. Dodo-
neine (1) was found to exhibit a vasorelaxant effect on
preconstricted rat aortic rings (IC = 81.4 0.9 mM).2 Its
structure was assigned on the basis of spectroscopic and
X-ray diffraction analyses. In spite of its interesting bio-
logical activities, only three syntheses3 have been reported
so far for the natural compound 1. No synthesis has been
reported for its 6-epimer, epidodoneine (2). In continua-
tion of our interest on the synthesis of bioactive lactones,4
we herein report the synthesis of dodoneine (1) and its 6-
epimer 2 (Figure 1).
This epoxide was subjected to Jacobsen’s hydrolytic ki-
netic resolution (HKR)6 by using (S,S)-Salen-Co-OAc
catalyst to give chiral epoxide 4 (43%) in highly enan-
tioenriched form (95% ee). Next, the epoxide 4 was treat-
ed with vinylmagnesium bromide in the presence of CuI
in THF at –20 °C to give the homoallyl alcohol 12 in 85%
yield. The relative stereochemistry of 1,3-diol in 12 was
established by their conversion to the corresponding ace-
tonide 13 after removal of MOM group. The syn relative
configuration of the hydroxy groups was confirmed by the
analysis of 13C NMR spectrum, which showed signals at
d = 19.8 and 30.0 for the two methyl groups and at d =
98.8 for the quaternary carbon.7
O
OH
O
The homoallyl alcohol 12 was esterified with acryloyl
chloride in the presence of Et3N to afford the acryloyl es-
ter 3 in 80% yield. Subsequent ring-closing metathesis of
ester 3 with Grubbs’ 1st generation catalyst8 in refluxing
CH2Cl2 for 12 hours afforded the a,b-unsaturated lactone
14 in 68% yield. To complete the synthesis, it was neces-
sary to remove the MOM group in compound 14. This
was achieved under neutral conditions using CeCl3·7H2O
in MeCN–MeOH (1:1)4j to afford the target lactone 1 in
79% yield (99.45% ee) (Scheme 2). The spectral data of
synthetic compound 1 was comparable with the reported
data.
HO
dodoneine 1
O
OH
O
HO
epidodoneine 2
Figure 1 Dodoneine (1) and its 6-epimer 2
In route b, the alcohol 7 was oxidized using IBX in
DMSO–CH2Cl2 to an aldehyde and chain elongated by
treatment with the two carbon stable ylide, (ethoxycarbo-
nylmethylene)triphenylphosphorane, to provide the a,b-
unsaturated ester 15 in 81%. MOM ether removal fur-
nished the secondary alcohol 6. The benzylidene acetal
(protected syn-1,3-diol) 5 was prepared in 60% yield by
base-catalyzed intramolecular conjugate addition using
benzaldehyde in the presence of potassium tert-butoxide
The retrosynthesis reveals that dodoneine (1) could be
synthesized in two ways from a common intermediate 7.
In route a, the lactone moiety can be constructed through
ring-closing metathesis (RCM), whereas in route b,
SYNTHESIS 2009, No. 19, pp 3285–3292
x
x.
x
x
.
2
0
0
9
Advanced online publication: 21.08.2009
DOI: 10.1055/s-0029-1216953; Art ID: Z04609SS
© Georg Thieme Verlag Stuttgart · New York

3286
G. Sabitha et al.
PAPER
O
O
OMOM
OH
O
OR
O
route a
MOMO
O
4
3 R = MOM
1
MOMO
HO
route b
Ph
OMOM
OH
O
O
O
OH
CO2Et
OEt
MOMO
7
5
6
HO
HO
O
O
OR
O
OR
O
OH
O
RO
RO
HO
9 R = MOM
2
8 R = MOM
Scheme 1 Retrosynthetic analysis for the synthesis of dodoneine (1) and its 6-epimer 2
OR
OR
OH
I
O
ref
a, b, c
OH
+
OPMB
RO
MOMO
RO
4: R = MOM
11
7: R = MOM
10
O
O
OH
OR
OR
O
OR
O
g
f
e
d
1
RO
RO
RO
3: R = MOM
14: R = MOM
12: R = MOM
h
O
O
13
HO
Scheme 2 Reagents and conditions: (a) IBX/DMSO, CH2Cl2, 0 °C to r.t., 5 h; (b) trimethylsulfonium iodide, DMSO, NaH, THF, 0 °C to r.t.,
6 h, 60%; (c) (S,S)-Jacobsen catalyst, AcOH, H2O, 12 h, 43%; (d) vinylmagnesium bromide, CuI, THF, 0 °C, 30 min, 85%; (e) acryloyl chloride,
anhyd Et3N, CH2Cl2, 30 min, 80% (f) Grubbs’ catalyst I, CH2Cl2, reflux, 12 h, 68%; (g) CeCl3·7H2O (20 mol%), MeCN–MeOH (1:1), reflux,
24 h, 79%; (h) i. CeCl3·7H2O (20 mol%), MeCN–MeOH (1:1), reflux, 24 h, ii. 2,2-DMP, acetone, PPTS, r.t., 2 h, 82%.
in THF at 0 °C for 2 hours and quenching the reaction to afford diastereomers in 1:1 ratio. Since the 6-epimer 2
with pH 7 buffer phosphate solution.9 Compound 5 was has a 1,3-anti relationship between two hydroxy centers
converted into the target molecule 1 (Scheme 3), which and in order to increase the diastereoselectivity in favor of
has been reported recently in the literature.3c
the requisite stereocenter (anti to the existing one), we
resorted to an oxidation-reduction protocol. Hence, the
alcohol was oxidized with Dess–Martin periodinane11 in
anhydrous CH2Cl2 at 0 °C to room temperature for 1 hour
to afford 9 in 90% yield (Scheme 4). Our next aim was the
selective reduction of ketone 9. Thus, the stereoselective
reduction of keto group was achieved with SmI2 in THF
and MeOH12 as proton source for 12 hours to afford the re-
After achieving the synthesis of the natural isomer, dodo-
neine (1), we attempted the synthesis of its 6-epimer 2 as
shown in Scheme 4. Thus, the primary alcohol 7 was oxi-
dized using IBX and the ensuing aldehyde was treated
with allylzinc bromide at 0 °C, which was preformed
from allyl bromide and zinc powder in anhydrous THF10
Synthesis 2009, No. 19, 3285–3292 © Thieme Stuttgart · New York

PAPER
Total Synthesis of (+)-Dodoneine and Its 6-Epimer
3287
OH
O
OMOM
O
c
d
OEt
OEt
a, b
MOMO
7
6
15
HO
Ph
O
O
CO2Et
ref. 3c
1
5
HO
Scheme 3 Reagents and conditions: (a) IBX/DMSO, CH2Cl2, 0 °C to r.t., 5 h; (b) Ph3P=CHCO2Et, benzene, 0 °C to r.t., 12 h, 81%; (c)
CeCl3·7H2O (20 mol%), MeCN–MeOH (1:1), reflux, 24 h, 77%; (d) PhCHO/t-BuOK, anhyd THF, –10 °C, 2 h, 62%.
O
OR
OR
OH
d
a, b, c
7
12
+
RO
16: R = MOM
9: R = MOM
RO
O
O
O
OR
O
OH
O
OR
O
g
e
f
16
HO
RO
RO
8: R = MOM
17: R = MOM
2
Scheme 4 Reagents and conditions: (a) IBX/DMSO, CH2Cl2, 0 °C to r.t., 5 h (b) allyl bromide, Zn, THF, 0 °C, 30 min, 89% (c) DMP,
NaHCO3, CH2Cl2, 0 °C to r.t., 1 h, 90% (d) SmI2, MeOH–THF, 73% (e) acryloyl chloride, anhyd Et3N, CH2Cl2, 30 min, 78% (f) Grubb’s cata-
lyst I, CH2Cl2, reflux, 79%, (g) CeCl3·7H2O (20 mol%), MeCN–MeOH (1:1), reflux, 24 h, 80%.
OR OH
i. CeCl3⋅7H2O, MeCN–MeOH (1:1)
O
O
reflux, 24 h
ii. 2, 2-DMP, acetone, PPTS
r.t., 84% (over two steps)
RO
16: R = MOM
HO
18
Scheme 5
25
quired anti-1,3-diastereomer as the major product. An- in 80% yield [99.28% ee, [a]D –26.7 (c 1.0, CHCl3)]
other isomer 12 was isolated in very small amount along (Scheme 4).
with 16. This compound 12 was identical in all respects as
that obtained from route a (optical rotation and 13C NMR
data).
Reactions were conducted under N2 in anhyd solvents such as
CH2Cl2, THF, and EtOAc. All reactions were monitored by TLC
(silica-coated plates and visualizing under UV light). Petroleum
ether (PE) used refers to the fraction boiling in the range 60–80 °C.
Yields refer to chromatographically and spectroscopically (1H and
13C NMR) homogeneous material. Air-sensitive reagents were
transferred by syringe or double-ended needle. Evaporation of sol-
vents was performed at reduced pressure on a Büchi rotary evapo-
The relative stereochemistry of 1,3-diol in 16 was estab-
lished by their conversion to the corresponding acetonide
18 after removal of MOM group (Scheme 5). The anti rel-
ative configuration of the hydroxy groups was confirmed
by the analysis of its 13C NMR spectrum, which showed
signals at 24.9 ppm for the two methyl groups and 100.5 rator. 1H and 13C NMR spectra of samples in CDCl3 were recorded
ppm for the quaternary carbon.7
on Varian FT-200 MHz (Gemini) and Bruker UXNMR FT-300
MHz (Avance) spectrometers. Chemical shifts d are reported rela-
The MOM protected homoallyl alcohol 16 was reacted
tive to TMS (d = 0.0) as an internal standard. Mass spectra were re-
with acryloyl chloride and diisopropylethylamine at 0 °C
in CH2Cl2 to afford ester 8 in 78% yield for ring-closing
metathesis. The ring-closing metathesis was achieved
with Grubbs’ 1st generation catalyst to afford lactone 17
in 79% yield, which was subjected to deprotection of
MOM with CeCl3·7H2O in MeCN–MeOH (1:1) at reflux
temperature for 24 hours to produce the epidodoneine (2)
corded under ESI conditions at 70 eV on LC-MSD (Agilent
technologies) spectrometers. All high-resolution spectra were re-
corded on QSTAR XL hybrid MS/MS system (Applied Biosys-
tems/MDS sciex, Foster City, CA, USA), equipped with an ESI
source (IICT, Hyderabad). Column chromatography was performed
on silica gel (60–120 mesh) supplied by Acme Chemical Co., India.
TLC was performed on Merck 60 F-254 silica gel plates. Optical ro-
Synthesis 2009, No. 19, 3285–3292 © Thieme Stuttgart · New York

3288
G. Sabitha et al.
PAPER
tations were measured with Jasco DIP-370 Polarimeter at 20 °C.
The % ee of the products was determined using Chiral HPLC,
Dionex (chromeleon, PDA).
HRMS (ESI): m/z calcd for C16H24O5 + Na (M+ + Na): 319.1521;
found: 319.1531.
The epoxide ring opened diol was eluted next and obtained as a light
25
yellow oil; yield: 611 mg (48%); Rf = 0.2 (PE–EtOAc, 1:1); [a]D
–48.3 (c 0.5, CHCl3).
(2S)-2-{(2S)-2-(Methoxymethoxy)-4-[4-(methoxymethoxy)phe-
nyl]butyl}oxirane (4)
To an ice-cooled solution of 2-iodoxybenzoic acid (4.33 g, 15.46
mmol) in DMSO (12 mL) was added a solution of 7 (2.2 g, 7.74
mmol) in anhyd CH2Cl2 (20 mL). The mixture was stirred at r.t. for
5 h, then filtered through a Celite pad (1 g), and washed with CH2Cl2
(4 × 20 mL). The combined organic filtrates were washed with H2O
(2 × 20 mL) and brine (2 × 20 mL), dried (Na2SO4), and concentrat-
ed in vacuo to afford the crude aldehyde. This was used in the next
step without further purification. A solution of NaH (0.46 g, 19.16
mmol) in DMSO (25 mL) was stirred at 70–75 °C for 30 min and
cooled to r.t. THF (30 mL) followed by the addition of a suspension
of trimethylsulfonium iodide (6.16 g, 30.18 mmol) in DMSO (5
mL) at –5 °C and the reaction mixture was stirred for 5 min. Then,
a solution of the above aldehyde in THF (5 mL) was added and the
mixture stirred for 4 h at –5 °C, The mixture was quenched with
H2O (20 mL) and extracted with CH2Cl2 (3 × 50 mL). The com-
bined organic layers were washed with H2O (2 × 20 mL) and brine
(2 × 20 mL), and dried (Na2SO4). The solvent was evaporated and
the residue purified by column chromatography (eluent: PE–
EtOAc, 7:3) to afford 2-{(2S)-2-(methoxymethoxy)-4-[4-(meth-
oxymethoxy)phenyl]butyl}oxirane (racemic) as a gummy liquid;
yield: 1.37 g (60%); Rf = 0.3 (PE–EtOAc, 7:3); [a]D25 +21.4 (c 1.4,
CHCl3).
Diol
IR (neat): 3421, 2939, 1610, 1510, 1232, 1151, 1078, 1011, 918,
830, 770 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.50–1.95 (m, 4 H), 2.59 (t, J = 8.3
Hz, 2 H), 3.15–3.27 (br s, 1 H), 3.36–3.50 (m, 1 H), 3.40 (s, 3 H),
3.45 (s, 3 H), 3.52–3.67 (br s, 1 H), 3.77–3.89 (m, 2 H), 4.64 (d,
J = 6.8 Hz, 1 H), 4.70 (d, J = 6.8 Hz, 1 H), 5.11 (s, 2 H), 6.90 (d,
J = 8.3 Hz, 2 H), 7.04 (d, J = 9.0 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 30.2, 36.3, 37.6, 55.7, 55.8, 66.4,
70.4, 76.3, 84.4, 95.3, 116.2, 129.0, 135.1, 155.2.
HRMS (ESI): m/z calcd for C16H26O6 + Na (M+ + Na): 337.1627;
found: 337.1627.
(4R,6S)-6-(Methoxymethoxy)-8-[4-(methoxymethoxy)phe-
nyl]oct-1-en-4-ol (12)
To a stirred solution of epoxide 4 (0.4 g, 13.5 mmol) in CH2Cl2 (60
mL) was added freshly prepared vinylmagnesium bromide (1.35
mL, 2 M) at –10 °C and the reaction mixture was stirred at the same
temperature for about 30 min. The reaction was quenched with aq
sat. NH4Cl (10 mL) and the mixture extracted with EtOAc (3 × 50
mL). The combined organic layers were washed with brine (2 × 50
mL), dried (Na2SO4), and concentrated under reduced pressure. Pu-
rification by column chromatography on silica gel (eluent: PE–
EtOAc, 7:3) afforded 12 as a thick syrup; yield: 371 mg (85%);
Rf = 0.25 (PE–EtOAc, 7:3); [a]D25 +39.5 (c 1, CHCl3).
2-{(2S)-2-(Methoxymethoxy)-4-[4-(methoxymethoxy)phe-
nyl]butyl}oxirane
IR (neat): 2926, 1611, 1510, 1232, 1151, 1079, 1034, 919, 832 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.68–1.92 (m, 4 H), 2.38–2.46 (m,
1 H), 2.51–2.77 (m, 3 H), 2.93–3.02 (m, 1 H), 3.39 (2 s, 6 H), 3.45
(s, 3 H), 3.67–3.82 (m, 1 H), 4.63 (d, J = 6.8 Hz, 1 H), 4.66 (d,
J = 6.8 Hz, 1 H), 5.10 (s, 2 H), 6.90 (d, J = 8.3 Hz, 2 H), 7.06 (d,
J = 8.3 Hz, 2 H).
13C NMR MHz, (75 MHz, CDCl3): d = 30.7 (2 C), 36.7 (2 C), 37.7
(2 C), 47.1 (2 C), 49.4 (2 C), 55.7, 55.9, 75.2 (2 C), 94.5, 95.7 (2 C),
116.3, 129.2, 135.3, 155.4.
IR (neat): 3454, 2932, 1611, 1510, 1443, 1232, 1151, 1079, 1010,
917, 824 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.64–1.70 (m, 2 H), 1.79–1.87 (m,
2 H), 2.21 (t, J = 6.2 Hz, 2 H), 2.55–2.62 (m, 2 H), 2.79 (br d, J = 2.0
Hz, 1 H, OH), 3.40 (s, 3 H), 3.45 (s, 3 H), 3.73–3.85 (m, 2 H), 4.63
(d, J = 6.8 Hz, 1 H), 4.70 (d, J = 6.8 Hz, 1 H), 5.11 (s, 2 H), 5.05–
5.14 (m, 2 H), 5.72–5.88 (m, 1 H), 6.90 (d, J = 8.7 Hz, 2 H), 7.05
(d, J = 8.7 Hz, 2 H).
HRMS (ESI): m/z calcd for C16H24O5 + Na (M+ + Na): 319.1521;
found: 319.1509.
13C NMR MHz, (100 MHz, CDCl3): d = 30.2, 36.3, 40.7, 42.1, 55.9
(2 C), 69.9, 77.0, 94.5, 95.2, 116.2, 117.7, 128.1, 129.1 (2 C), 134.7.
A mixture of (S,S)-(+)-N,N¢-bis(3,5-di-tert-butylsalicylidene)-1,2-
cyclohexanediaminocobalt(II) (12 mg, 0.02 mmol) in toluene (0.04
mL, 0.40 mmol) and AcOH (0.005 mL, 0.08 mmol) was stirred
while open to the air for 1 h at r.t. The reaction mixture was concen-
trated under reduced pressure and the brown residue was dried un-
der vacuum. To the residue was added the above obtained racemic
epoxide (1.2 g, 4.05 mmol) in one portion at 0 °C and then H2O
(0.036 mL, 2.0 mmol) was added. The mixture was allowed to
warm to r.t. and stirred for 12 h. The residue was purified by column
chromatography (eluent: PE–EtOAc, 7:3). (S)-Oxirane 4 was eluted
first and obtained as a colorless liquid; yield: 510 mg (43%);
Rf = 0.3 (PE–EtOAc, 7:3); [a]D25 –20.8 (c 1.75, CHCl3).
HRMS (ESI): m/z calcd for C18H28O5 + Na (M+ + Na): 347.1834;
found: 347.1818.
4-{2-[(4S,6R)-6-Allyl-2,2-dimethyl-1,3-dioxan-4-yl]ethyl}phe-
nol (13)
To a stirred solution of compound 12 (0.08 g, 0.25 mmol) in a mix-
ture of MeOH (3 mL) and MeCN (3 mL) was added a catalytic
amount of CeCl3·7H2O (18 mg, 0.05 mmol) under N2. After stirring
for 12 h at reflux temperature, the reaction mixture was quenched
with solid NaHCO3 (0.05 g) and filtered, the solvent was removed
under reduced pressure and the residue was purified by silica gel
column chromatography (eluent: PE–EtOAc, 4:6) to afford the pure
precursor 1,3-diol; yield: 47 mg (82%); Rf = 0.3 (PE–EtOAc, 4:6);
[a]D25 –16.0 (c 0.35, CHCl3).
4
IR (neat): 2941, 1611, 1511, 1233, 1151, 1080, 1035, 920, 832 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.61–1.73 (m, 2 H), 1.79–1.94 (m,
2 H), 2.5 (dd, J = 4.9, 2.6 Hz, 1 H), 2.54–2.75 (m, 2 H), 2.80 (t,
J = 4.5 Hz, 1 H), 3.01–3.08 (m, 1 H), 3.42 (s, 3 H), 3.47 (s, 3 H),
3.82 (m, 1 H), 4.71 (d, J = 7.0 Hz, 1 H), 4.73 (d, J = 6.7 Hz, 1 H),
5.15 (s, 2 H), 6.96 (d, J = 8.7 Hz, 2 H), 7.11 (d, J = 8.5 Hz, 2 H).
Precursor 1,3-Diol
1H NMR (300 MHz, CDCl3): d = 1.46–1.81 (m, 4 H), 2.17–2.28 (m,
2 H), 2.50–2.71 (m, 2 H), 3.55 (br s, 1 H), 3.82–3.95 (m, 2 H), 5.05–
5.15 (m, 2 H), 5.68–5.84 (m, 1 H), 6.73 (d, J = 8.5 Hz, 2 H), 6.97
(d, J = 8.3 Hz, 2 H), 7.12 (br s, 1 H).
13C NMR (75 MHz, CDCl3): d = 30.6, 36.9, 37.9, 47.4, 49.5, 55.6,
55.8, 75.2, 94.5, 95.8, 116.2, 129.2, 135.3, 155.4.
13C NMR (75 MHz, CDCl3): d = 30.6, 39.5, 41.9, 42.3, 71.9, 72.2,
115.4, 118.3, 129.3, 133.3, 134.0, 154.1.
Synthesis 2009, No. 19, 3285–3292 © Thieme Stuttgart · New York

PAPER
Total Synthesis of (+)-Dodoneine and Its 6-Epimer
3289
LCMS: m/z = 259 (M+ + Na).
1H NMR (300 MHz, CDCl3): d = 1.80–1.92 (m, 2 H), 2.11–2.32 (m,
2 H), 2.30–2.48 (m, 2 H), 2.56–2.74 (m, 2 H), 3.38 (s, 3 H), 3.48 (s,
3 H), 3.75–3.85 (m, 1 H), 4.55–4.73 (m, 1 H), 4.66 (s, 2 H), 5.15 (s,
2 H), 6.03 (dt, J = 9.8 Hz, 1 H), 6.84–6.92 (m, 1 H), 6.96 (d, J = 8.5
Hz, 2 H), 7.11 (d, J = 8.5 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 29.5, 30.6, 36.3, 39.5, 55.8, 55.9,
73.9, 75.1, 94.6, 96.4, 116.3, 121.5, 129.2, 135.2, 145.0, 155.4,
164.2.
To a solution of above obtained 1,3-diol (0.03 g, 0.12 mmol) in an-
hyd acetone (3 mL) was added 2,2-dimethoxypropane (2,2-DMP,
0.03 mL, 0.25 mmol) and PPTS (10 mol%) were added. The mix-
ture was stirred at r.t. for 2 h, then aq NaHCO3 was added to neu-
tralize PPTS and filtered. Removal of solvent and purification by
silica gel column chromatography (eluent: PE–EtOAc, 7:3) afford-
ed the acetonide 13 as a clear liquid; yield: 28 mg (82%); Rf = 0.5
(PE–EtOAc, 7:3); [a]D25 –11.0 (c 0.55, CHCl3).
HRMS (ESI): m/z calcd for C19H26O6 + Na (M+ + Na): 373.1627;
found: 373.1619.
13
IR (neat): 3371, 2993, 2940, 2865, 1612, 1443, 1381, 1203, 1169,
(+)-Dodoneine (1)
996, 919, 832, 758 cm–1.
To a stirred solution of compound 14 (0.06 g, 0.17 mmol) in a mix-
ture of MeOH (10 mL) and MeCN (10 mL) was added a catalytic
amount of CeCl3·7H2O (13 mg, 0.034 mol) under N2. After stirring
for 12 h at reflux temperature, the reaction mixture was quenched
with solid NaHCO3 (0.1 g) and filtered, the solvent was removed
under reduced pressure, and the residue was purified by silica gel
column chromatography (PE–EtOAc, 4:6) to afford compound 1 as
a solid; yield: 34 mg (79%); Rf = 0.2 (PE–EtOAc, 4:6); [a]D25 +40.3
(c 0.4, CHCl3).
1H NMR (300 MHz, CDCl3): d = 1.35–1.46 (m, 2 H), 1.37 (s, 6 H),
1.52–1.66 (m, 1 H), 1.68–1.81 (m, 1 H), 2.05–2.17 (m, 1 H), 2.20–
2.31 (m, 1 H), 2.48–2.70 (m, 2 H), 3.64–3.83 (m, 2 H), 4.49–4.64
(br s, 1 H, OH), 4.97–5.07 (m, 2 H), 5.67–5.82 (m, 1H), 6.67 (d,
J = 8.5 Hz, 2 H), 6.98 (d, J = 8.3 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 19.8, 30.0 (2 C), 36.3, 38.0, 40.6,
67.8, 68.7, 98.8, 115.1, 117.2, 129.4 (2 C), 133.6, 133.9, 153.8.
LCMS: m/z = 299 (M+ + Na).
IR (KBr): 3418, 2923, 2854, 1715, 1513, 1221, 1049, 915, 838, 762
cm–1.
1H NMR (300 MHz, CDCl3): d = 1.69–2.05 (m, 5 H), 1.89–2.01,
2.33–2.43 (m, 3 H), 2.60–2.77 (m, 2 H), 3.83–3.93 (m, 1 H), 4.60–
4.69 (m, 1 H), 6.04 (dt, J = 9.8, 1.7 Hz, 1 H), 6.78 (d, J = 8.5 Hz, 2
H), 6.89–6.93 (m, 1 H), 7.05 (d, J = 8.3 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 29.6, 30.9, 39.5, 42.2, 68.8, 77.4,
115.5, 121.3, 129.6, 133.6, 145.6, 154.2, 164.5.
HRMS (ESI): m/z calcd for C15H18O4 + Na (M+ + Na): 285.1102;
found: 285.1115.
(1R)-1-{(2S)-2-(Methoxymethoxy)-4-[4-(methoxymethoxy)phe-
nyl]butyl}but-3-enyl Acrylate (3)
Acryloyl chloride (0.1 mL, 1.10 mmol) was added dropwise under
N2 to a solution of compound 12 (0.25 g, 0.77 mmol), Et3N (0.22
mL, 1.48 mmol), and DMAP (0.05 mmol) in anhyd CH2Cl2 (10
mL). The mixture was stirred at r.t. for 30 min. After completion of
reaction, the mixture was poured into brine (15 mL) and extracted
with CH2Cl2 (2 × 15 mL). The combined organic phases were
washed with aq 1 M HCl (6 mL) and brine (2 × 5 mL), dried
(Na2SO4), and evaporated under reducer pressure. The crude prod-
uct was purified by column chromatography on silica gel (PE–
EtOAc, 8:2) to give 3 as a liquid; yield: 232 mg (80%); Rf = 0.5
(PE–EtOAc, 8:2); [a]D25 +8.0 (c 0.75, CHCl3).
Ethyl (E,5S)-5-(Methoxymethoxy)-7-[4-(methoxymethoxy)phe-
nyl]hept-2-enoate (15)
To an ice-cooled solution of 2-iodoxybenzoic acid (4.33 g, 15.46
mmol) in DMSO (12 mL) was added a solution of 7 (2.2 g 7.74
mmol) in anhyd CH2Cl2 (20 mL). The mixture was stirred at r.t. for
5 h, then filtered through a Celite pad (1 g) and washed with CH2Cl2
(4 × 20 mL). The combined organic filtrates were washed with H2O
(2 × 20 mL) and brine (2 × 20 mL), dried (Na2SO4), and concentrat-
ed in vacuo to afford the crude aldehyde. This was used in the next
step without further purification. To a solution of the above ob-
tained aldehyde (2.0 g, 4.830 mmol) in CH2Cl2 (30 mL) was added
(methoxycarbonylmethylene)triphenylphosphorane (2.0 g, 5.797
mmol) and the reaction mixture was stirred for 2 h at r.t. The com-
pletion of the reaction was monitored by TLC. CH2Cl2 was removed
under reduced pressure, the residue was dissolved in Et2O (25 mL)
and PE (20 mL) was added. The crystallized Ph3PO was filtered off
and the filtrate was concentrated to dryness. The crude product was
chromatographed on silica gel (PE–EtOAc, 7:3) to afford the pure
ester 15 as a colorless liquid; yield: 2.2 g (81%); Rf = 0.6 (PE–
EtOAc, 7:3); [a]D25 –21.8 (c 0.5, CHCl3).
IR (neat): 2929, 2825, 1722, 1614, 1510, 1406, 1196, 1035, 919,
811 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.66–1.99 (m, 4 H), 2.36 (t, J = 6.8
Hz, 2 H), 2.59 (t, J = 7.5 Hz, 2 H), 3.38 (s, 3 H), 3.45 (s, 3 H), 3.53–
3.63 (m, 1 H), 4.59 (d, J = 5.2 Hz, 1 H), 4.62 (d, J = 7.5 Hz, 1 H),
5.02–5.18 (m, 3 H), 5.10 (s, 3 H), 5.65–5.85 (m, 1 H), 5.80 (dt,
J = 10.6, 1.5 Hz, 1 H), 6.08 (dd, J = 10.6, 3.8 Hz, 1 H), 6.36 (dt,
J = 17.4, 2.3 Hz, 1 H), 6.89 (d, J = 9.0 Hz, 2 H), 7.04 (d, J = 8.3 Hz,
2 H).
13C NMR (75 MHz, CDCl3): d = 30.5, 36.2, 38.2, 38.8, 55.7, 55.8,
70.7, 74.3, 94.5, 95.6, 116.2, 118.1, 128.6, 129.2, 130.6, 133.2,
135.3, 155.3, 165.6.
HRMS (ESI): m/z calcd for C21H30O6 + Na (M+ + Na): 401.1940;
found: 401.1928.
(6R)-6-{(2S)-2-(Methoxymethoxy)-4-[4-(methoxymethoxy)phe-
nyl]butyl}5,6-dihydro-2H-2-pyranone (14)
IR (neat): 2931, 1719, 1654, 1511, 1447, 1233, 1151, 1080, 1035,
920, 828 cm–1.
Grubbs’s catalyst (30 mg, 0.03 mmol, 10 mol%) was dissolved in
CH2Cl2 (10 mL) and added dropwise to a refluxing solution of the
acrylic ester 3 (140 mg, 0.37 mmol) in CH2Cl2 (100 mL). Refluxing
was continued for 12 h by which time all of the starting material was
consumed (TLC). The solvent was removed under aspirator vacu-
um, and the crude product was purified by silica gel column chro-
matography (PE–EtOAc, 7:3) to obtain of 14 as a colorless liquid;
yield: 87 mg (68%); Rf = 0.2 (PE–EtOAc, 7:3); [a]D25 +70.4 (c 0.6,
CHCl3).
1H NMR (300 MHz, CDCl3): d = 1.28 (t, J = 7.2 Hz, 3 H), 1.67–1.91
(m, 2 H), 2.47 (t, J = 7.3 Hz, 2 H), 2.52–2.76 (m, 2 H), 3.39 (s, 3 H),
3.47 (s, 3 H), 3.67–3.77 (m, 1 H), 4.18 (q, J = 7.2 Hz, 2 H), 4.89 (d,
J = 5.8 Hz, 1 H), 4.91 (d, J = 5.8 Hz, 1 H), 5.15 (s, 2 H), 5.87 (dt,
J = 15.7 Hz, 1 H), 6.94 (dd, J = 15.5, 7.5 Hz, 1 H), 6.96 (d, J = 8.5
Hz, 2 H), 7.10 (d, J = 8.7 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 14.2, 29.6, 30.8, 36.5, 55.7, 55.9,
60.2, 75.8, 95.7, 116.3, 123.7, 129.2, 135.1, 144.8, 155.4, 178.0.
IR (neat): 2942, 1722, 1611, 1510, 1388, 1240, 1151, 1080, 1031,
920, 820 cm–1.
Synthesis 2009, No. 19, 3285–3292 © Thieme Stuttgart · New York

3290
G. Sabitha et al.
PAPER
HRMS (ESI): m/z calcd for C19H28O6 + Na (M+ + Na): 375.1783;
found: 375.1771.
was allowed to warm to r.t. After 30 min, the mixture was cooled to
0 °C and quenched with aq sat. NH4Cl (2 × 10 mL). The mixture
was filtered through a pad of Celite and washed with EtOAc (2 × 15
mL). Concentration of the filtrate gave a residue, which was puri-
fied by silica gel chromatography (PE–EtOAc, 7:3) to give (6S)-6-
(methoxymethoxy)-8-[4-(methoxymethoxy)phenyl]oct-1-en-4-ol as
a pale yellow liquid; yield: 2.22 g (89%); Rf = 0.25 (PE–EtOAc,
7:3).
Ethyl (E,5S)-5-Hydroxy-7-(4-hydroxyphenyl)hept-2-enoate (6)
To a stirred solution of compound 15 (0.3 g, 0.59 mmol) in a mix-
ture of MeOH (5 mL) and MeCN (5 mL) was added a catalytic
amount of CeCl3·7H2O under N2. After stirring for 12 h at reflux
temperature, the reaction mixture was quenched with solid NaHCO3
(0.5 g) and filtered, the solvent was removed under reduced pres-
sure, and the residue was purified by silica gel column chromatog-
raphy (PE–EtOAc, 4:6) to afford compound 6; yield: 1.15 g (77%);
Rf = 0.2 (PE–EtOAc, 4:6); [a]D25 –10.1 (c 0.55, CHCl3).
(6S)-6-(Methoxymethoxy)-8-[4-(methoxymethoxy)phenyl]oct-
1-en-4-ol
1H NMR (400 MHz, CDCl3): d = 1.57–1.94 (m, 3 × CH2), 2.21 (t,
J = 6.6 Hz, 2 H), 2.52–2.63 (m, 2 H), 3.40 (2 s, 2 × CH3), 3.45 (s, 3
H), 3.74–3.92 (m, 2 H), 5.05–5.12 (m, 2 H), 5.10 (s, 2 H), 5.74–5.87
(m, 1 H), 6.90 (d, J = 8.8 Hz, 2 H), 7.04 (d, J = 8.8 Hz, 2 H).
IR (neat): 3387, 2923, 2852, 1696, 1652, 1515, 1450, 1369, 1223,
1042, 980, 828 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.30 (t, J = 7.5 Hz, 3 H), 1.74 (q,
J = 7.5 Hz, 2 H), 2.29–2.42 (m, 2 H), 2.25–2.76 (m, 2 H), 3.67–3.76
(m, 1 H), 4.17 (q, J = 6.7 Hz, 2 H), 4.75 (br s, 1 H, OH), 5.85 (d,
J = 15.10 Hz, 1 H), 6.69 (d, J = 8.3 Hz, 2 H), 6.90 (dd, J = 15.10,
7.5 Hz, 1 H), 7.0 (d, J = 9.0 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 14.2, 31.0, 38.8, 40.3, 60.5, 69.8,
115.3, 124.0, 129.4, 133.4, 145.0, 154.0.
13C NMR (75 MHz, CDCl3): d = 30.2, 30.8, 36.3, 36.8, 40.7, 40.8,
42.0, 42.1, 55.8, 67.1, 69.8, 75.6, 76.9, 94.5 (2 C), 95.2, 96.4, 116.2,
117.5, 117.7, 129.1, 134.6, 134.8, 135.2, 155.3.
To a stirred solution of above obtained racemic compound (2 g, 6.17
mmol) in anhyd CH2Cl2 (50 mL), Dess–Martin periodinane (3.14 g,
7.4 mmol) was added at 0 °C and stirred for 1 h at r.t. The reaction
mixture was quenched with 1:1 ratio of aq sat. NaHCO3 and aq
Na2S2O3 (5 mL) and allowed to stir for 30 min and extracted with
CH2Cl2 (2 × 50 mL). The combined organic layers were washed
with H2O (2 × 20 mL), dried (Na2SO4), and concentrated. The crude
residue was purified by column chromatography on silica gel (PE–
EtOAc, 7:3) to give 9 as a yellow liquid; yield: 1.78 g (90%);
Rf = 0.35 (PE–EtOAc, 7:3); [a]D25 +5 (c 0.45, CHCl3).
HRMS (ESI): m/z calcd for C15H20O4 + Na (M+ + Na): 287.1259;
found: 287.1249.
Ethyl 2-[(4S,6S)-6-(4-Hydroxyphenethyl)-2-phenyl-1,3-dioxan-
4-yl]acetate (5)
To a solution of alcohol 6 (700 mg, 2.65 mmol) in anhyd THF (50
mL) at 0 °C was added distilled benzaldehyde (0.29 mL, 2.91
mmol), followed by t-BuOK (30 mg, 0.26 mmol). The yellow solu-
tion was stirred for 15 min at 0 °C. The addition of benzaldehyde/
t-BuOK was repeated twice and the mixture was allowed to warm
to r.t. after which the reaction was quenched with pH 7 phosphate
buffer (25 mL). The layers were separated, and the aqueous layer
was extracted with Et2O (4 × 30 mL). The combined organic layers
were washed with brine (2 × 15 mL), dried (Na2SO4), filtered, and
concentrated in vacuo and purified by column chromatography
(PE–EtOAc, 7:3) to obtain 5 as a colorless oil; yield: 600 mg (62%);
Rf = 0.5 (PE–EtOAc, 7:3); [a]D25 –247 (c 0.3, CHCl3).
9
IR (neat): 2926, 2854, 1669, 1629, 1510, 1444, 1233, 1150, 1080,
1014, 919, 830, 771 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.80 (q, J = 8.3 Hz, 2 H), 1.91
(d, J = 6.8 Hz, 2 H), 2.52–2.72 (m, 3 H), 2.88 (dd, J = 15.9, 6.7 Hz,
1 H), 3.34 (s, 3 H), 3.45 (s, 3 H), 4.02–4.11 (m, 1 H), 4.58 (d, J = 7.5
Hz, 1 H), 4.65 (d, J = 6.8 Hz, 1 H), 5.10 (s, 2 H), 6.10 (dd, J = 15.9,
1.5 Hz, 1 H), 6.74–6.86 (m, 2 H), 6.89 (d, J = 9.0 Hz, 2 H), 7.05 (d,
J = 8.3 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 18.4, 30.8, 37.2, 45.5, 55.6, 55.8,
74.3, 94.5, 96.3, 116.3, 129.2, 132.6, 135.2, 142.6, 155.6, 197.6.
HRMS (ESI): m/z calcd for C18H26O5 + Na (M+ + Na): 345.1677;
found: 345.1672.
IR (neat): 3419, 2922, 2855, 1714, 1613, 1514, 1218, 1021, 767,
699 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.26 (t, J = 7.2 Hz, 3 H), 1.41–1.55
(m, 2 H), 1.69 (dt, J = 12.8, 2.45 Hz, 2 H), 1.72–1.83 (m, 2 H), 1.89–
2.03 (m, 2 H), 2.50 (dd, J = 15.5, 6.0 Hz, 2 H), 2.62–2.82 (m, 2 H),
3.75–3.87 (m, 1 H), 4.17 (q, J = 7.2 Hz, 2 H), 4.22–4.34 (m, 1 H),
5.54 (s, 1 H), 6.74 (d, J = 8.5 Hz, 2 H), 7.04 (d, J = 8.5 Hz, 2 H),
7.31–7.40 (m, 2 H), 7.44–7.53 (m, 2 H).
13C NMR (75 MHz, CDCl3): d = 14.17, 30.2, 36.5, 37.5, 41.0, 60.7,
73.2, 75.5, 100.5, 115.2, 126.0, 128.1, 128.6, 129.5, 130.1, 132.7,
138.5, 152.8, 171.0.
(4S,6S)-8-(4-Hydroxyphenyl)-6-(methoxymethoxy)oct-1-en-4-
ol (16)
To a stirred suspension of 9 (1.5 g, 4.65 mmol) in THF (15 mL) at
r.t. was added MeOH (5.6 mL, 139.68 mmol) followed by dropwise
addition of SmI2 (6.6 g, 16.33 mmol) in anhyd THF (5 mL). The re-
sulting mixture was stirred for 12 h before the septum was removed
and stirring was continued until the color of the solution was
changed. The solution was then quenched with aq sat. Na2S2O3 (15
mL) and diluted with EtOAc (50 mL). The layers were separated
and the organic layer was washed with aq sat. Na2S2O3 (2 × 30 mL).
The organic layer was then washed with H2O (2 × 50 mL), dried
(Na2SO4), and concentrated. Purification of this material was ac-
complished by chromatography on silica gel (eluent: PE–EtOAc,
7:3) to give 16 as a pale yellow liquid; yield: 1.09 g (73%); Rf = 0.25
(PE–EtOAc, 7:3); [a]D25 +16.4 (c 0.5, CHCl3).
HRMS (ESI): m/z calcd for C22H26O5 + Na (M+ + Na): 393.1677;
found: 393.1662.
(6S)-8-(4-Hydroxyphenyl)-6-(methoxymethoxy)oct-1-en-4-one
(9)
To an ice-cooled solution of 2-iodoxybenzoic acid (4.33 g, 15.46
mmol) in DMSO (12 mL) was added a solution of 7 (2.2 g 7.74
mmol) in anhyd CH2Cl2 (20 mL). The mixture was stirred at r.t. for
5 h, then filtered through a Celite pad (1 g), and washed with CH2Cl2
(4 × 20 mL). The combined organic filtrates were washed with H2O
(2 × 20 mL) and brine (2 × 20 mL), dried (Na2SO4), and concentrat-
ed in vacuo to afford the crude aldehyde. This was used in the next
step without further purification. To the above obtained aldehyde
and Zn (1.25 g, 19.23 mmol) in anhyd THF (25 mL) was added allyl
bromide (1.0 mL, 11.57 mmol) dropwise at 0 °C and the mixture
IR (neat): 3451, 2934, 1612, 1510, 1232, 1151, 1079, 1010, 917,
825 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.62–1.68 (m, 2 H), 1.72–1.98 (m,
2 H), 2.25 (t, J = 6.6 Hz, 2 H), 2.51–2.70 (m, 2 H), 2.89 (br s, 1 H,
OH), 3.42 (s, 3 H), 3.47 (s, 3 H), 3.81–4.0 (m, 2 H), 4.69 (s, 2 H),
5.07–5.18 (m, 2 H), 5.15 (s, 2 H), 5.77–5.92 (m, 1 H), 6.96 (d,
J = 8.7 Hz, 2 H), 7.10 (d, J = 8.7 Hz, 2 H).
Synthesis 2009, No. 19, 3285–3292 © Thieme Stuttgart · New York

PAPER
Total Synthesis of (+)-Dodoneine and Its 6-Epimer
3291
13C NMR (75 MHz, CDCl3): d = 30.8, 36.9, 40.9, 42.0, 55.9 (2 C),
67.1, 75.7, 94.5, 96.4, 116.3, 117.5, 129.1, 134.9, 135.2, 155.4.
4-{2-[(4S,6S)-6-Allyl-2,2-dimethyl-1,3-dioxan-4-yl]ethyl}phe-
nol (18)
Compound 18 was prepared from 16 (0.07 mg, 0.22 mmol) follow-
ing the procedure described for compound 13 as a colorless liquid;
yield: 49 mg (84%); [a]D25 +16.0 (c 0.35, CHCl3).
HRMS (ESI): m/z calcd for C18H28O5 + Na (M+ + Na): 347.1834;
found: 347.1836.
(1S)-1-[(2S)-4-(4-Hydroxyphenyl)-2-(methoxymethoxy)bu-
tyl]but-3-enyl Acrylate (8)
Compound 8 was prepared from 16 (900 mg, 2.77 mmol) following
1H NMR (300 MHz, CDCl3): d = 1.30 (s, 3 H), 1.33 (s, 3 H), 1.50–
1.83 (m, 4 H), 2.08–2.31 (m, 2 H), 2.45–2.73 (m, 2 H), 3.63–3.89
(m, 2 H), 4.96–5.11 (m, 2 H), 5.64–5.84 (m, 1 H), 6.67 (d, J = 8.5
Hz, 2 H), 6.99 (d, J = 8.5 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 24.8 (2 C), 30.7, 37.6, 38.0, 40.0,
65.9, 66.3, 100.5, 115.2, 116.9, 129.4, 133.8, 134.3, 153.7.
the procedure described for compound 3 as a colorless liquid; yield:
25
0.81 g (78%); Rf = 0.5 (PE–EtOAc, 8:2); [a]D +28.0 (c 0.75,
CHCl3).
IR (neat): 2927, 1722, 1613, 1510, 1270, 1195, 1152, 1079, 1012,
919, 812, 771 cm–1.
LCMS: m/z = 299 ((M+ + Na).
1H NMR (300 MHz, CDCl3): d = 1.71–1.88 (m, 4 H), 2.36 (t, J = 6.7
Hz, 2 H), 2.58 (t, J = 8.3 Hz, 2 H), 3.33 (s, 3 H), 3.45 (s, 3 H), 3.57
(q, J = 11.3, 5.2 Hz, 1 H), 4.53 (d, J = 6.7 Hz, 1 H), 4.61 (d, J = 6.7
Hz, 1H), 5.10 (s, 2 H), 5.02–5.17 (m, 3 H), 5.80 (dd, J = 10.5, 1.5
Hz, 1 H), 5.67–5.83 (m, 1 H), 6.07 (dd, J = 17.4, 10.5 Hz, 1 H), 6.36
(dd, J = 17.4, 2.2 Hz, 1 H), 6.89 (d, J = 9.0 Hz, 2 H), 7.04 (d, J = 9.0
Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 30.3, 36.9, 38.7, 39.2, 55.7, 55.9,
70.6, 74.2, 94.6, 96.2, 116.2, 118.0, 128.7, 129.1, 130.5, 133.2,
135.4, 155.4, 165.6.
Acknowledgment
V.B.R thanks UGC and S.S.S.R thanks CSIR, New Delhi for the
award of fellowships.
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(5) Lescure, P.; Huet, F. Synthesis 1987, 404.
HRMS (ESI): m/z calcd for C21H30O6 + Na (M+ + Na): 401.1940;
found: 401.1916.
(6S)-6-{(2S)-2-(Methoxymethoxy)-4-[4-(methoxymethoxy)phe-
nyl]butyl}5,6-dihydro-2H-2-pyranone (17)
Compound 17 was prepared from 8 (650 mg, 1.71 mmol) following
the procedure described for compound 14 as a colorless liquid;
yield: 0.470 g (79%); [a]D25 –16.5 (c 1, CHCl3).
IR (neat): 2932, 2825, 1721, 1611, 1510, 1387, 1238, 1150, 1079,
1031, 919, 819 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.74–2.07 (m, 4 H), 2.32–2.38 (m,
2 H), 2.62 (t, J = 8.3 Hz, 2 H), 3.39 (s, 3 H), 3.48 (s, 3 H), 3.92–4.01
(m, 1 H), 4.62–4.73 (m, 1 H), 4.71 (s, 2 H), 5.15 (s, 2 H), 6.04 (dt,
J = 9.6, 1.7 Hz, 1 H), 6.86–6.93 (m, 1 H), 6.96 (d, J = 8.5 Hz, 2 H),
7.11 (d, J = 8.7 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 29.8, 30.1, 37.0, 40.4, 55.6, 55.8,
73.7, 74.6, 94.4, 96.3, 116.2, 121.3, 129.0, 130.2, 145.0, 155.3,
164.1.
HRMS (ESI): m/z calcd for C19H26O6 + Na (M+ + Na): 373.1627;
found: 373.1619.
(–)-Epidodoneine (2)
Compound 2 was prepared from 17 (120 mg, 0.034 mmol) follow-
ing the procedure described for compound 1 as a solid; yield: 71 mg
(80%); Rf = 0.2 (PE–EtOAc, 4:6); [a]D25 –26.7 (c 1.0, CHCl3).
(6) (a) Schaus, S. E.; Brandes, B. D.; Larrow, J. F.; Tokunaga,
M.; Hansen, K. B.; Gould, A. E.; Furrow, M. E.; Jacobsen,
E. N. J. Am. Chem. Soc. 2002, 124, 1307. (b) Louis, J. T.;
Nelson, W. L. J. Org. Chem. 1987, 52, 1309.
IR (neat): 3406, 2921, 2855, 1710, 1511, 1395, 1266, 1114, 1058,
831, 704 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.54–1.70 (m, 2 H), 1.77–1.87 (m,
2 H), 2.25–2.45 (m, 1 H), 2.49–2.59 (m, 1 H), 2.60–2.71 (m, 2 H),
3.72–3.84 (m, 1 H), 4.54 (br s, 1 H, OH), 4.65–4.75 (m, 1 H), 5.98
(dt, J = 10.3, 2.5 Hz, 1 H), 6.88–7.0 (m, 1 H), 6.65 (d, J = 6.9 Hz, 2
H), 6.95 (d, J = 7.8 Hz, 2 H).
13C NMR MHz, (75 MHz, CDCl3): d = 29.0, 29.9, 39.5, 41.8, 64.2,
74.0, 114.3, 120.1, 128.1, 131.5, 144.6, 154.3, 163.0.
(7) Rychnovsky, S. D.; Rogers, B. N.; Richardson, R. I. Acc.
Chem. Res. 1998, 31, 9.
(8) (a) Fürstner, A. Angew. Chem. Int. Ed. 2000, 39, 3012.
(b) Tanaka, T. M.; Grubbs, R. H. Acc. Chem. Res. 2001, 34,
18. (c) Grubbs, R. H. Tetrahedron 2004, 44, 2449.
(d) Grubbs, R. H. Tetrahedron 2004, 60, 7117. (e) Love, J.
A. In Handbook of Metathesis, Vol. 2; Grubbs, R. H., Ed.;
Wiley-VCH: Weinheim, 2003, 296–322.
HRMS (ESI): m/z calcd for C15H18O4 + Na (M+ + Na): 285.1102;
(9) Evans, D. A.; Gauchet-Prunet, J. A. J. Org. Chem. 1993, 58,
2446.
found: 285.1090.
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PAPER
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Synthesis 2009, No. 19, 3285–3292 © Thieme Stuttgart · New York