Total synthesis of a diarylheptanoid, rhoiptelol B

Article abstract of DOI:10.1002/ejoc.200901041

A stereoselective total synthesis of rhoiptelol B has been accomplished for the first time. The four asymmetric centers were efficiently generated through Keck allylation, Jacobson epoxidation Aldol reaction and reductive etherification as the key steps.

Full text of DOI:10.1002/ejoc.200901041

FULL PAPER
DOI: 10.1002/ejoc.200901041
Total Synthesis of a Diarylheptanoid, Rhoiptelol B
Chada Raji Reddy,*[a] Nagavaram Narsimha Rao,[a] and Boinapally Srikanth[a]
Keywords: Rhoiptelol B / Total synthesis / Natural products / Reductive etherification / Aldol reactions
A stereoselective total synthesis of rhoiptelol B has been ac-
complished for the first time. The four asymmetric centers
were efficiently generated through Keck allylation, Jacobson
epoxidation Aldol reaction and reductive etherification as the
key steps.
Introduction
Diarylheptanoids constitute an important class of natu-
ral products due to their interesting biological and pharma-
cological properties (antiinflammatory, antioxidant, anti-
cancer, inhibition of nitric oxide production, DPPH-radical
scavenging activity, etc.).[1] The structure of diarylheptano-
ids is either cyclic or linear. Predominantly, diarylheptano-
ids containing a tetrahydropyran (THP) ring such as
centrolobines,[2] calyxins,[3] diospongins[4] and others[5] have
found substantial interest to medicinal as well as synthetic
organic chemists.
Rhoiptelol B (1, Figure 1), a diarylheptanoid containing
a tetrahydropyran ring, was first isolated in 1996 from the
fruits of Rhoiptelea chiliantha along with other two diaryl-
heptanoids.[6] Later, in 2007 it was also isolated from the
bark of Alnus hirsuta (which has been traditionally em-
ployed as a herbal medicine for the treatment of inflamma-
tory diseases in Asia) and investigated for their inhibitory
activity against LPS-induced NF-kB activation, NO and
TNF-α production and HIF-1 in AGS cells.[7,8] Till date
there is no report on synthesis of rhoiptelol B. The interest-
ing structural feature of this molecule is presence of a chiral
hydroxy group on adjacent carbon to tetrahydropyran ring,
which is not present in any other diarylheptanoids contain-
ing a THP-ring. The above observations combined with our
interest on diarylheptanoids[2u] have driven us for the syn-
thesis of rhoiptelol B (1).
Figure 1. Structure of rhoiptelol B.
Alder reaction,[2n,3b] palladium mediated cyclization,[2o,4d]
FeCl3-mediated cyclization,[2p] radical cyclization,[2q] Mait-
land–Japp reaction,[2r,2s] olefin metathesis,[2t] etc. However,
Keck allylation, Aldol reaction followed by reductive etheri-
fication sequence has not been utilized for the synthesis of
THP-ring diarylheptanoids. Herein, we presented the first
total synthesis of rhoiptelol B.
Results and Discussion
The strategy we have used for the rhoiptelol B (Scheme 1)
involves the tetrahydropyran ring formation using reductive
etherification of an oxidative derivative of aldol product 2,
which can be obtained via lithium-mediated aldol reaction
of aldehyde 3 and α-benzyloxy ketone 4. Access to these
two intermediate fragments 3 was envisioned starting from
vanillin (5) using Keck allylation and fragment 4 from ben-
zylchavicol (6) using Jacobson epoxidation and Wacker oxi-
dation as the key steps.
The synthesis of the aldehyde 3 was started through the
tosylation of vanillin (5) followed by Keck allylation under
(R)-BINOL-Ti(OiPr)4 conditions[9] to yield the homoallylic
alcohol 8 in 70% yield.[10] The free hydroxy group of 8 was
protected as tert-butyldimethyl silyl ether 9 (95%), which
was subjected to dihydroxylation (OsO4, NMO) followed by
sodium periodate oxidation to provide the aldehyde 3 in
83% yield over two steps (Scheme 2).
A variety of approaches have been devised for the synthe-
sis of THP-ring containing diarylheptanoids, which involves
the tetrahydropyran ring formation as the key step. This
was achieved using a different sequence of reactions such
as Prins cyclization,[2a–2f,3a,4e,4f,5] reductive etherifi-
cation,[2g–2m,4b,4g] oxa-Michael reaction,[2m,4a,4c,4h,4i] Diels–
[a] Organic Division-I (NPL), Indian Institute of Chemical Tech-
nology,
Hyderabad 500607, India
Fax: +91-040-27160512
E-mail: rajireddy@iict.res.in
Eur. J. Org. Chem. 2010, 345–351
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
345

C. R. Reddy, N. N. Rao, B. Srikanth
FULL PAPER
Scheme 1. Retrosynthetic analysis of rhoiptelol B (1).
Scheme 3. Synthesis of ketone fragment (4).
Having both aldehyde 3 and ketone 4 fragments in hand,
our next task was to do the lithium-mediated aldol reaction
followed by the conversion of aldol product to tetra-
Scheme 2. Synthesis of aldehyde fragment (3).
Next, the synthesis of benzyloxy ketone fragment 4
(Scheme 3) was begun with the known benzylchavicol (6),
which can be obtained in two steps using reported proto-
col.[11] Thus, epoxidation of benzylchavicol (6) using
mCPBA furnished the epoxide 10 in 81% yield. Resolution
of racemic epoxide 10 to chiral epoxide 10a has been ac-
complished using Jacobsen resolution method.[12] This reso-
lution reaction provided the chiral epoxide 10a along with
the diol 10b in 44% and 46% yields, respectively. However,
the diol 10b was also converted into the required epoxide
10a using a well-known sequence.[13] The enantiomeric ex-
cess of this epoxide 10a was confirmed at a later stage inter-
mediate (11) by chiral HPLC.[14] As anticipated, the treat-
ment of epoxide 10a with trimethylsulfonium iodide in pres-
ence of n-BuLi as a base in THF at –20 °C revealed the
allyl alcohol 11 in 88% yield.[15] The benzyl protection of
allylic alcohol 11 using benzyl bromide/NaH gave 12 (92%
yield), which was then subjected to modified Wacker oxi-
dation[16,17] to obtain the desired ketone fragment 4 in 63%
yield.[18]
Scheme 4. Synthesis of rhoiptelol B from 3 and 4.
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Total Synthesis of a Diarylheptanoid, Rhoiptelol B
tions were performed under an atmosphere of nitrogen in flame-
or oven-dried glassware with magnetic stirring.
hydropyran ring. Thus, the treatment of ketone 4 with lith-
ium bis(trimethylsilyl)amide at –78 °C followed by the ad-
dition of aldehyde 3 at the same temperature gave the cou-
pled product 2 in 65% yield as mixture of diastereomers.[19]
This inseparable mixture of diastereomers was oxidized
4-Formyl-2-methoxyphenyl-4-methylbenzenesulfonate (7): To
a
stirred solution of vanillin 5 (5 g, 32.8 mmol) in dichloromethane
(65 mL) at 0 °C was added triethylamine (3.31 g, 32.8 mmol) fol-
using Dess–Martin periodinane to the corresponding β-di- lowed by p-toluenesulfonyl chloride (6.26 g, 32.8 mmol). Then, the
reaction temperature was raised to 25 °C and stirred for 2 h. The
reaction was diluted with 1  HCl (30 mL) and the layers were
separated. The organic layer was further washed with 1  HCl
(2ϫ20 mL) followed by saturated aqueous NaHCO3 (20 mL) and
with brine (20 mL). The combined organic layers were dried with
Na2SO4, filtered, and concentrated under reduced pressure. The
crude residue was purified by flash chromatography (15% ethyl
acetate in hexanes) to give 7 (9.3 g, 93%) as a color less solid; m.p.
ketone 13 in 92% yield, which was entirely existed as the
enol ketone (confirmed by 1H NMR).[20] Then, the reaction
of 13 with pTsA in CH2Cl2 was promoted the silyl ether
cleavage followed by cyclization and dehydration reactions
to yield dihydropyranone 14 in 81% yield.[21] Subsequently,
the selective reduction of olefin and debenzylation of 14
was accomplished in one-pot under hydrogenation reaction
conditions to afford tetrahydropyranone 15 (74% yield) as
a single isomer.[22] LS-Selectride reduction of the tetra-
126–128 °C. IR (KBr): ν
= 2922, 2851, 1699, 1596, 1422, 1149,
˜
max
1
1115, 1029, 857, 713 cm–1. H NMR (300 MHz, CDCl3): δ = 9.91
hydropyranone 15 provided the desired alcohol 16 in 84% (s, 1 H, CHO), 7.75 (d, J = 8.3 Hz, 2 H, Ar-H), 7.46–7.28 (m, 5 H,
Ar-H), 3.63 (s, 3 H, OCH3), 2.4 (s, 3 H, Ar-CH3) ppm. 13C NMR
(75 MHz): δ = 190.7, 152.4, 145.4, 142.8, 135.6, 132.6, 129.4, 128.4,
124.3, 124.1, 110.9, 55.6, 21.5 ppm. HRMS (ESI): (m/z) calcd. for
C15H14O5NaS, 329.0459 [M + Na]+; found 329.0456.
yield with a 10:1 diastereoselectivity.[23] The compound 16
was extensively characterized by nOe studies.[24] Finally, de-
tosylation of 16 with K2CO3 in MeOH under refluxing con-
ditions afforded the rhoiptelol B (1), (Scheme 4). The spec-
troscopic data (1H NMR, 13C NMR and mass) of synthetic
(R)-4-(1-Hydroxybut-3-enyl)-2-methoxyphenyl-4-methylbenzenesul-
fonate (8): To the stirred solution of oven-dried 4-Å molecular
sieves (10 g) in CH2Cl2 (40 mL) under N2 atmosphere, was added
(S)-BINOL (0.93 g, 3.2 mmol) a 1.0  solution of Ti(OiPr)4 (0.4 g,
1.63 mmol) in CH2Cl2 and a freshly prepared 1.0  solution of
TFA (13 mg, 0.11 mmol) in CH2Cl2. The reaction mixture was
heated at reflux for a period of 3 h, and then allowed to cool to
room temperature. Aldehyde 7 (5 g, 16.3 mmol) in CH2Cl2 (20 mL),
was added to the reaction mixture. After the mixture stirred for
0.5 h at room temperature, cooled to –78 °C, allyltributyltin
(6.5 mL, 21.2 mmol) was slowly added. The reaction mixture as
stirred for an additional 10 min at –78 °C, then kept in a –20 °C
freezer. After 4 d, the reaction mixture was filtered through a pad
of celite in to a 500 mL flask that contained a stirring saturated
aqueous NaHCO3 solution (50 mL) and the resulting mixture was
stirred for 1 h, then the layers were separated. The aqueous layer
was extracted with CH2Cl2 (2ϫ20 mL). The combined organic lay-
ers were washed with brine (20 mL), dried with Na2SO4, filtered,
and concentrated under reduced pressure to give the crude product.
The crude residue was purified by column chromatography (12%
ethyl acetate in hexanes) to give 8 (4.0 g, 70%) as a colorless oil:
rhoiptelol was identical and the optical rotation {[α]D28
=
+77.2 (c = 0.2, MeOH)} was comparable with the reported
data for natural product.[6,7]
Conclusions
In conclusion, we have accomplished the first total syn-
thesis of rhoiptelol B in 15 steps in a convergent fashion.
The key steps used were Keck allylation, Jacobson resolu-
tion, lithium-mediated aldol reaction and reductive etherifi-
cation for the generation of required chiral centers. Further
elaboration of this sequence of reactions to construct the
other tetrahydropyran ring containing biologically active
compounds is underway in our laboratory.
Experimental Section
[α]2D5 = +17 (c = 1.0, CHCl ). IR (KBr): ν
= 3541, 2931, 1600,
˜
3
max
1
General: H NMR and 13C NMR spectra were recorded either in
1502, 1369, 1273, 1175, 1034, 847, 753, 661 cm–1 1H NMR
.
CDCl3 or in [D4]MeOH solvent on 300 MHz, 500 MHz or 75 MHz
spectrometer at ambient temperature. Chemical shifts δ is given in
ppm, coupling constant J are in Hz. The chemical shifts are re-
ported in ppm on scale downfield from TMS as internal standard
and signal patterns are indicated as follows: s, singlet; d, doublet;
dd, doublet of doublet; td, triplet of doublet; t, triplet; m, mul-
tiplet;br. s, broad singlet. FTIR spectra were recorded as thin films
on KBr or neat. Optical rotations were measured on digital polari-
meter using a 1 mL cell with a 1 dm path length. For low (MS)
and High (HRMS) resolution, m/z ratios are reported as values in
atomic mass units. HPLC was done using Eurocel 01, chiral IA
columns and 2-propanol and hexane as eluents. All the reagents
and solvents were reagent grade and used without further purifica-
tion unless specified otherwise. Technical grade ethyl acetate and
petroleum ether used for column chromatography were distilled
prior to use. Tetrahydrofuran (THF) when used as solvent for the
reactions was freshly distilled from sodium benzophenone ketyl.
Column chromatography was carried out using silica gel (60–
120 mesh & 100–200 mesh) packed in glass columns. All the reac-
(300 MHz, CDCl3): δ = 7.72 (d, J = 8.3 Hz, 2 H, Ar-H), 7.27 (d,
J = 8.3 Hz, 2 H, Ar-H), 7.06 (d, J = 8.3 Hz, 1 H, Ar-H), 6.86 (d,
J = 1.5 Hz, 1 H, Ar-H), 6.80 (dd, J = 8.3, 2.2 Hz, 1 H, Ar-H),
5.84–5.68 (m, 1 H, CH=CH2), 5.18–5.09 (m, 2 H,CH2=CH), 4.68–
4.61 (m, 1 H, CHOH), 3.57 (s, 3 H, OCH3), 2.52–2.33 (m, 2 H,
CH2-CH=CH2), 2.45 (s, 3 H, Ar-CH3) ppm. 13C NMR (75 MHz):
δ = 151.6, 145.0, 144.3, 137.3, 134.1, 133.1, 129.3, 128.5, 123.6,
118.5, 117.8, 110.1, 72.6, 55.5, 43.8, 21.6 ppm. HRMS (ESI): (m/z)
calcd. for C18H24NO5S, 366.1375 [M + NH4]+; found 366.1377.
(R)-4-[1-(tert-Butylmethylsilyloxy)but-3-enyl]-2-methoxyphenyl-4-
methylbenzenesulfonate (9): To a stirred solution of alcohol 8 (4.0 g,
11.4 mmol), in CH2Cl2 (40 mL) was added imidazole (1.17 g,
17.2 mmol) and DMAP (140 mg, 1.14 mmol) fallowed by tert-
butyldimethylsilyl chloride (2.0 g, 13.2 mmol) at 0 °C. Then the reac-
tion temperature was raised to room temperature and stirred for
24 h. After the addition of saturated aqueous NaHCO3 (20 mL),
the mixture was extracted with CH2Cl2 (2ϫ20 mL). The combined
organic layers were washed with brine (20 mL), dried with Na2SO4,
Eur. J. Org. Chem. 2010, 345–351
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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347

C. R. Reddy, N. N. Rao, B. Srikanth
FULL PAPER
filtered, and concentrated under reduced pressure. The crude resi-
due was purified by column chromatography (5% ethyl acetate in
hexanes) to give 9 (5.0 g, 95%) as a colorless oil. [α]2D8 = +23.8 (c
69.9, 52.5, 46.7, 37.7 ppm. HRMS (ESI): (m/z) calcd. for
C16H16O2Na, 263.1047 [M + Na]+; found 263.1058.
(S)-2-[4-(Benzyloxy)benzyl]oxirane (10a): Glacial acetic acid
(0.0043 mL, 0.748 mmol with respect to catalyst) was added to a
reddish orange solution of (S,S)-(+)-N,NЈ-bis(3,5-di-tert-butylsali-
cylidene)-1,2-cyclohexanediamino-cobalt(II) (226 mg, 0.375 mmol)
in toluene (5 mL) at room temperature and the resulting solution
was stirred for 1 h at room temperature in a flask open to the air.
The reaction solution was then evaporated in vacuo, affording a
brown solid. Racemic epoxide 10 (6.0 g, 25.0 mmol) in dry THF
(6 mL) was added to this solid, and the resulting brown-black solu-
tion was stirred for 10 min at 0 °C before distilled water (0.247 mL,
13.75 mmol) was added. The resulting solution was vigorously
stirred at 0 °C for an additional 5 min before it was warmed to
room temperature and stirred for a further 18 h. solvent was re-
moved under vacuum. Purified by column chromatography (5%
ethyl acetate in hexanes) gives enantio-enriched epoxide 10a
(2.64 g, 44%) along with diol 10b (2.9 g, 46%). See spectroscopic
data for 10a epoxide above. [α]3D0 = +0.9 (c = 1.0, CHCl3). Diol
= 1.0, CHCl ). IR (KBr): ν
= 2931, 2856, 1600, 1502, 1373,
˜
3
max
1
1176, 1089, 840, 778, 660 cm–1. H NMR (300 MHz, CDCl3): δ =
7.69 (d, J = 8.3 Hz, 2 H, Ar-H), 7.24 (d, J = 8.3 Hz, 2 H, Ar-H),
7.08 (d, J = 8.3 Hz, 1 H, Ar-H), 6.79 (d, J = 1.5 Hz, 1 H, Ar-H),
6.73 (dd, J = 8.3, 2.2 Hz, 1 H, Ar-H), 5.78–5.62 (m, 1 H,
CH=CH2), 5.03–4.93 (m, 2 H, CH2=CH), 4.62–4.56 (m, 1 H,
CHOSi), 3.52 (s, 3 H, OCH3), 2.44 (s, 3 H, Ar-CH3), 2.42–2.24 (m,
2 H, CH2-CH=CH2), 0.86 [s, 9 H, (CH3)3Si], 0.02 (s, 3 H, CH3Si),
–0.15 (s, 3 H, CH3Si) ppm. 13C NMR (75 MHz): δ = 151.6, 145.6,
145.0, 137.2, 134.9, 133.2, 129.3, 128.9, 123.6, 118.0, 117.4, 110.2,
74.6, 55.5, 45.5, 25.9, 21.8, 18.3, –4.5, –4.7 ppm. HRMS (ESI):
(m/z) calcd. for C24H38NO5SSi, 480.2234 [M + NH4]+; found
480.2241.
(R)-4-[1-(tert-Butylmethylsilyloxy)-3-oxopropyl]-2-methoxyphenyl-
4-methylbenzenesulfonate (3): To a solution of silyl ether 9 (3.5 g,
7.5 mmol) in 40 mL mixture of acetone/water (3:1) was added OsO4
(0.48 mL, 4% aqueous solution, 0.075 mmol) and NMO (1.06 g,
9.0 mmol) at 25 °C and stirred at for 5 h. The solvent was evapo-
rated and the residue was extracted with ethyl acetate (30 mL). The
organic layers were washed with brine (20 mL), dried with Na2SO4
and concentrated in vacuo. To a solution of above crude diol in
50 mL mixture of THF/H2O (4:1) was added NaIO4 (3.2 g,
15.0 mmol) and the reaction mixture was stirred at 25 °C for 1 h.
The solid was removed by filtration and the filtrate was extracted
with ethyl acetate (30 mL). The organic layers were washed with
brine (20 mL), dried with Na2SO4 and concentrated in vacuo. The
crude aldehyde was purified by flash chromatography (15% ethyl
acetate in hexanes) to give aldehyde 3 (2.9 g, 83%) as a colorless
(10b): m.p. 70–72 °C. [α]2D6 = +9.3 (c = 1.0, CHCl ). IR (KBr): ν
˜
3
max
= 3454, 2905, 1639, 1512, 1247, 1014, 810, 771, 696 cm–1. 1H NMR
(300 MHz, CDCl3): δ = 7.48–7.28 (m, 5 H, Ar-H), 7.13 (d, J =
8.5 Hz, 2 H, Ar-H), 6.93 (d, J = 8.5 Hz, 2 H, Ar-H), 5.05 (s, 2 H,
Ar-CH2-O), 3.95–3.84 (m, 1 H, CH-OH), 3.73–3.63 (m, 1 H, CH2-
OH), 3.56–3.45 (m, 1 H, CH2-OH), 2.79–2.62 (m, 2 H, Ar-CH2),
2.15 (br. s, 1 H, OH), 2.07 (br. s, 1 H, OH) ppm. 13C NMR
(75 MHz): δ = 157.3, 136.9, 130.2, 130.0, 128.4, 127.8, 127.3, 114.8,
73.1, 69.9, 65.7, 38.6 ppm. HRMS (ESI): (m/z) calcd. for
C16H18O3Na, 281.1153 [M + Na]+; found 281.1141.
(S)-1-[4-(Benzyloxy)phenyl]but-3-en-2-ol (11): A solution of tri-
methylsulfonium iodide (6.8 g, 33.3 mmol) in THF (65 mL) was
cooled to –20 °C, nBuLi (2.5  solution in hexane, 12.6 mL,
31.2 mmol) was added drop wise and the resulting solution was
stirred for 1 h at –20 °C. A solution of the epoxide 10a (2.0 g,
8.3 mmol) in THF (10 mL) was added and a cloudy suspension
was formed. The stirring was continued for another 1 h at –20 °C.
The reaction mixture was cooled to 0 °C and quenched with water
(20 mL). The layers were separated and the aqueous layer was ex-
tracted with diethyl ether (2ϫ50 mL). The combined organic layers
were dried with Na2SO4 and concentrated under reduced pressure.
Purification of crude compound by flash chromatography (8%
ethyl acetate in hexanes) gave alcohol 11 (1.86 g, 88%) as a pale
oil. [α]3D0 = +27.3 (c = 1.0, CHCl ). IR (KBr): νmax= 2931, 2856,
˜
3
1726, 1600, 1502, 1371, 1176, 1093, 843, 779, 661 cm–1. H NMR
1
(300 MHz, CDCl3): δ = 9.76 (t, J = 2.2 Hz, 1 H, CHO) 7.72 (d, J
= 8.3 Hz, 2 H, Ar-H), 7.28 (d, J = 8.3 Hz, 2 H, Ar-H), 7.12 (d, J
= 8.3 Hz, 1 H, Ar-H), 6.86 (d, J = 1.5 Hz, 1 H, Ar-H), 6.82 (dd, J
= 8.3, 2.2 Hz, 1 H, Ar-H), 5.17 (dd, J = 8.1, 3.9 Hz, 1 H, CHOSi),
3.53 (s, 3 H, OCH3), 2.87–2.76 (m, 1 H, CH2-CHO), 2.65–2.56 (m,
1 H, CH2-CHO), 2.44 (s, 3 H, Ar-CH3), 0.86 [s, 9 H, (CH3)3Si], 0.04
(s, 3 H, CH3Si), –0.14 (s, 3 H, CH3Si) ppm. 13C NMR (75 MHz): δ
= 200.6, 151.7, 144.9, 144.1, 137.4, 133.0, 129.2, 128.6, 123.9, 117.5,
109.7, 70.0, 55.4, 53.8, 25.6, 21.6, 18.0 –4.7, –5.1 ppm. HRMS
(ESI): (m/z) calcd. for C23H36NO6SSi, 482.2027 [M + NH4]+; found
482.2036.
yellow oil. [α]2D6 = +3.3 (c = 1.0, CHCl ). IR (KBr): ν
= 3413,
˜
3
max
2922, 1610, 1510, 1239, 1018, 738, 696 cm–1. H NMR (300 MHz,
CDCl3): δ = 7.45–7.27 (m, 5 H, Ar-H), 7.14 (d, J = 8.5 Hz, 2 H,
Ar-H), 6.92 (d, J = 8.5 Hz, 2 H, Ar-H), 5.98–5.85 (m, 1 H,
CH=CH2), 5.23 (td, J = 17.0, 1.3 Hz, 1 H, CH2=CH), 5.12 (td, J
= 10.3, 1.3 Hz, 1 H, CH2=CH), 5.00 (s, 2 H, Ar-CH2-O), 4.29 (q,
J = 6.6 Hz, 1 H, CH-OH), 2.87–2.66 (m, 2 H, Ar-CH2) ppm. 13C
NMR (75 MHz): δ = 157.5, 140.1, 137.0, 130.4, 130.3, 130.2, 129.8,
129.5, 127.8, 127.4, 115.0, 114.8, 73.6, 69.9, 42.8 ppm. HRMS
(ESI): (m/z) calcd. for C17H22NO2, 272.1645 [M + NH4]+; found
272.1647.
1
2-[4-(Benzyloxy)benzyl]oxirane (10): To a solution of benzyl chav-
icol 6 (10.0 g, 44.6 mmol) in CH2Cl2 (50 mL) was added m-chloro-
perbenzoic acid (14.0 g, 80.0 mmol) at 0 °C in small portions. The
reaction mixture was stirred for an additional 5 min at 0 °C, then
warmed up to room temperature and stirring was continued for
another 3 h at this temperature. Saturated aqueous NaHSO3
(100 mL) was added to the reaction mixture at 0 °C. The aqueous
layer was extracted with CH2Cl2 (2ϫ30 mL) and the organic phase
was dried with Na2SO4. Concentration of the organic phase under
vacuum gave crude epoxide, which was purified by flash
chromatography (5% ethyl acetate in hexanes) to obtain epoxide
(S)-1-(Benzyloxy)-4-[2-(benzyloxy)but-3-enyl]benzene (12): NaH
(139.8 mg, 5.82 mmol) was washed with hexane (3ϫ2 mL), sus-
pended in THF (15 mL) and cooled to 0 °C. Alcohol 11 (740 mg,
10 (8.6 g, 81%) as a white solid; m.p. 50–52 °C. IR (KBr): ν
=
˜
max
2920, 2853, 1616, 1510, 1239, 1019, 835, 739 cm–1. 1H NMR 2.91 mmol) in THF (10 mL) was added drop wise into the reaction
(300 MHz, CDCl3): δ = 7.45–7.27 (m, 5 H, Ar-H), 7.16 (d, J =
8.5 Hz, 2 H, Ar-H), 6.92 (d, J = 8.5 Hz, 2 H, Ar-H), 5.00 (s, 2 H,
Ar-CH2-O), 3.15–3.07 (m, 1 H, CH-O), 2.90–2.70 (m, 3 H, Ar-CH,
and the solution stirred for 10 min at 0 °C. Benzyl bromide
(0.52 mL, 4.36 mmol) was added slowly, followed by TBAI
(107.5 mg, 0.29 mmol). The reaction was warmed to room tem-
CH2-O), 2.51 (dd, J = 4.9, 2.6 Hz, 1 H, Ar-CH) ppm. 13C NMR perature and stirred for 12 h. Saturated NH4Cl was added to
(75 MHz): δ = 157.5, 136.9, 129.9, 129.3, 128.4, 127.8, 127.3, 114.7,
quench the reaction at 0 °C and the reaction mixture was warmed
348
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Total Synthesis of a Diarylheptanoid, Rhoiptelol B
to room temperature. The layers were separated and the aqueous vacuo. The residue was purified by column chromatography (15%
layer was further extracted with ethyl acetate (15 mL). The com- ethyl acetate in hexanes) to give β-diketone 13 (412 mg, 92%) as a
bined organic layers were dried with Na2SO4 and concentrated un- viscous liquid. [α]2D5 = –5.5 (c = 1.0, CHCl ). IR (KBr): ν
=
˜
3
max
der reduced pressure. Purification by flash chromatography (5% 2929, 2856, 1727, 1603, 1507, 1373, 1247, 1175, 1091, 835, 748, 698
1
ethyl acetate in hexanes) gave benzyl ether 12 (922 mg, 92%) as a cm–1. H NMR (300 MHz, CDCl3): δ = 7.71 (d, J = 8.3 Hz, 2 H,
pale yellow oil. –[α]3D0 = –20.5 (c = 1.0, CHCl ). IR (KBr): ν
=
Ar-H), 7.47–7.05 (m, 15 H, Ar-H), 6.93–6.80 (m, 4 H, Ar-H), 5.86
˜
3
max
2921, 2854, 1610, 1509, 1238, 1068, 736, 696 cm–1. 1H NMR (s, 1 H, CH=COH), 5.13–5.01 (m, 1 H, CH2OSi), 5.06 (s, 2 H, Ar-
(300 MHz, CDCl3): δ = 7.49–7.16 (m, 10 H, Ar-H), 7.12 (d, J = CH2-O), 4.60–4.46 (m, 1 H, Ar-CH-O), 4.32–4.21 (m, 1 H, Ar-CH-
8.5 Hz, 2 H, Ar-H), 6.89 (d, J = 8.5 Hz, 2 H, Ar-H), 5.85–5.69 (m, O), 3.98–3.90 (m, 1 H, CH-OBn), 3.52 (s, 3 H, OCH3), 3.01–2.78
1 H, CH=CH2), 5.25–5.09 (m, 2 H, CH2=CH), 5.00 (s, 2 H, Ar- (m, 2 H, CH2-CO), 2.66–2.47 (m, 2 H, Ar-CH2), 2.43 (s, 3 H, Ar-
CH2-O), 4.58 (d, J = 12.0 Hz, 1 H, Ar-CH-O), 4.32 (d, J = 12.0 Hz, CH3), 0.82 [s, 9 H, (CH3)3Si], –0.02 (s, 3 H, CH3Si), –0.17 (s, 3 H,
1 H, Ar-CH-O) 3.91 (q, J = 6.6 Hz, 1 H, CH-OBn), 2.91 (dd, J = CH3Si) ppm. 13C NMR (75 MHz): δ = 195.3, 190.6, 157.5, 151.6,
13.7, 7.3 Hz, 1 H, Ar-CH), 2.75 (dd, J = 13.7, 5.8 Hz, 1 H, Ar- 144.8, 144.6, 137.3, 137.0, 133.0, 130.4, 129.7, 129.6, 129.1, 128.6,
CH) ppm. 13C NMR (75 MHz): δ = 157.3, 138.5, 138.2, 137.1, 128.5, 128.2, 127.8, 127.6, 127.5, 127.4, 117.5, 114.6, 109.7, 98.5,
130.7, 130.5, 128.5, 128.3, 128.1, 127.8, 127.7, 127.5, 127.4, 127.2, 82.4, 72.2, 71.8, 69.9, 55.4, 49.9, 39.3, 25.6, 21.6, 18.0, –4.8, –5.3
117.3, 114.4, 81.5, 70.1, 69.9, 41.3 ppm. HRMS (ESI): (m/z) calcd. ppm. HRMS (ESI): (m/z) calcd. for C47H54NaO9SSi, 845.3150 [M
for C24H28NO2, 362.2115 [M + NH4]+; found 362.2122.
+ Na]+; found 845.3162.
4-((R)-6-{(S)-1-(Benzyloxy)-2-[4-(benzyloxy)phenyl]ethyl}-4-oxo-
3,4-dihydro-2H-pyran-2-yl)-2-methoxyphenyl 4-Methylbenzenesul-
fonate (14): To a stirred solution of β-diketone 13 (400 mg,
0.48 mmol) in CH2Cl2 (2 mL) was added pTsOH (9.2 mg,
0.048 mmol) at room temperature. The reaction was stirred for 24 h
and then quenched by the addition of saturated NaHCO3 (2 mL).
The layers were separated and the aqueous phase was extracted
with CH2Cl2 (5 mL). The combined organic layers were washed
with brine (3 mL), dried with Na2SO4 and concentrated in vacuo.
The crude compound was purified by flash chromatography (30%
ethyl acetate in hexanes) to give cyclized compound 14 (271 mg,
81%) as a pale yellow viscous liquid. [α]2D9 = –39.9 (c = 1.0, CHCl3).
(S)-3-(Benzyloxy)-4-[4-(benzyloxy)phenyl]butan-2-one (4): To
a
solution of alkene 12 (850 mg, 2.47 mmol) in MeOH (17 mL)
added mercuric acetate (944.9 mg, 2.96 mmol) was stirred at room
temperature for overnight. Then the reaction mixture was transfer-
red to a solution of LiCl (205 mg, 4.94 mmol), PdCl2 (438 mg,
2.47 mmol) and CuCl2 (996.6 mg, 7.41 mmol) in MeOH (8 mL)
and was further stirred at 55 °C for 3 h. Saturated NaHCO3
(20 mL) was added, and the product was extracted with diethyl
ether (3ϫ25 mL). The organic extracts were dried with Na2SO4
and concentrated. The crude product was purified by flash
chromatography (8% ethyl acetate in hexanes) to furnish methyl
ketone 4 (560 mg, 63%) as a colorless oil. [α]3D1 = –34.9 (c = 0.66,
IR (KBr): ν = 2924, 2865, 1669, 1606, 1508, 1372, 1176, 1091,
˜
max
CHCl ). IR (KBr): νmax = 2922, 2854, 1714, 1612, 1509, 1237, 1104,
˜
3
848, 748, 661 cm–1. H NMR (500 MHz, CDCl3): δ = 7.78 (d, J =
1
1021, 742, 696 cm–1. H NMR (300 MHz, CDCl3): δ = 7.42–7.21
1
8.3 Hz, 2 H, Ar-H), 7.42 (t, J = 7.2 Hz, 2 H, Ar-H), 7.38 (t, J =
7.2 Hz, 2 H, Ar-H), 7.34–7.24 (m, 6 H, Ar-H), 7.21–7.16 (m, 1 H,
Ar-H) 7.14 (d, J = 8.3 Hz, 2 H, Ar-H), 7.09 (d, J = 8.3 Hz, 2 H,
Ar-H), 6.87 (d, J = 8.3 Hz, 2 H, Ar-H), 6.85–6.77 (m, 2 H, Ar-H),
5.63 (s, 1 H, CH-CO), 5.31 (dd, J = 13.5, 4.1 Hz, 1 H, Ar-CH-O),
5.04 (s, 2 H, Ar-CH2-O), 4.61–4.53 (m, 1 H, Ar-CH-O), 4.42–4.35
(m, 1 H, Ar-CH-O), 4.05 (t, J = 6.2 Hz, 1 H, CH-OBn), 3.58 (s, 3
H, OCH3), 3.03–2.92 (m, 2 H, CH2-CO), 2.78–2.54 (m, 2 H, Ar-
CH2), 2.44 (s, 3 H, Ar-CH3) ppm. 13C NMR (75 MHz): δ = 191.7,
174.6, 157.6, 152.0, 145.1, 138.4, 137.9, 137.1, 136.8, 133.1, 130.4,
129.4, 128.9, 128.5, 128.4, 128.3, 127.9, 127.7, 127.6, 127.4, 124.2,
118.1, 114.6, 110.4, 104.3, 80.2, 79.8, 72.0, 69.9, 55.6, 42.7, 39.3,
21.6 ppm. HRMS (ESI): (m/z) calcd. for C41H39O8S, 691.2360 [M
+ Na]+; found 691.2348.
(m, 8 H, Ar-H), 7.17–7.12 (m, 2 H, Ar-H), 7.09 (d, J = 8.5 Hz, 2
H, Ar-H), 6.84 (d, J = 8.5 Hz, 2 H, Ar-H), 5.03 (s, 2 H, Ar-CH2-
O), 4.48 (d, J = 11.7 Hz, 1 H, Ar-CH-O), 4.36 (d, J = 11.7 Hz, 1
H, Ar-CH-O), 3.87 (dd, J = 7.5, 4.7 Hz, 1 H, CH-OBn), 2.95–2.78
(m, 2 H, Ar-CH2), 2.07 (s, 3 H, CH3-CO) ppm. 13C NMR
(75 MHz): δ = 210.8, 157.6, 137.3, 137.0, 130.4, 129.2, 128.5, 128.3,
127.8, 127.7, 127.6, 127.4, 114.7, 85.9, 72.5, 69.9, 37.5, 26.0 ppm.
HRMS (ESI): (m/z) calcd. for C24H28NO3, 378.2064 [M + NH4]+;
found 378.2076.
4-{(1R,6S)-6-(Benzyloxy)-7-[4-(benzyloxy)phenyl]-1-(tert-butyldi-
methylsilyloxy)-3,5-dioxoheptyl}-2-methoxyphenyl 4-Methylbenz-
enesulfonate (13): To a stirred solution of ketone 4 (360 mg,
1.0 mmol) in THF (3 mL) at –78 °C was added drop wise a solution
of lithium bis(trimethylsilyl)amide (1  in THF, 1.5 mL, 1.5 mmol).
After stirring at –78 °C for 45 min, aldehyde 3 (696 mg, 1.5 mmol)
in THF (3 mL) was added. The resulting solution was stirred at
–78 °C for another 45 min and was then quenched with saturated
NH4Cl (3 mL), two layers were separated. The aqueous layer was
extracted with ethyl acetate (10 mL) and the combined organic ex-
tracts were washed with brine (3 mL), dried with Na2SO4 and con-
centrated in vacuo. The residue was purified by column chromatog-
raphy (15% ethyl acetate in hexanes) to give aldol adduct 2 as a
mixture of diastereomers.
4-{(2R,6S)-6-[(S)-1-Hydroxy-2-(4-hydroxyphenyl)ethyl]-4-oxotetra-
hydro-2H-pyran-2-yl}-2-methoxyphenyl 4-Methylbenzenesulfonate
(15): Palladium on carbon (100 mg, 10% wet weight) was added to
a solution of compound 14 (200 mg) in EtOAc (2 mL). The reac-
tion mixture was stirred overnight under hydrogen atmosphere. Af-
ter the completion of reaction, the mixture was filtered through
celite and the resulting filtrate was concentrated in vacuo. Column
chromatography of the residue on silica gel (50% ethyl acetate in
hexanes) gave compound 15 (109 mg, 74%) as an amorphous col-
orless solid. m.p. 58–60 °C. [α]2D8 = +36.5 (c = 0.5, CHCl3). IR
To a stirred solution of diastereomeric mixture of aldol adduct 2 (KBr): νmax = 3379, 2924, 2854, 1750, 1602, 1511, 1369, 1174, 1030,
˜
(450 mg, 0.54 mmol) in dry CH2Cl2 (5.4 mL) was added NaHCO3 846, 816, 715, 661 cm–1. 1H NMR (300 MHz, CDCl3): δ = 7.79 (d,
(91.7 mg, 1.09 mmol) and Dess–Martin periodinane (347 mg, J = 8.3 Hz, 2 H, Ar-H), 7.33 (d, J = 8.3 Hz, 2 H, Ar-H), 7.12 (d,
0.81 mmol) in one portion. The mixture was stirred for 1 h at room J = 8.3 Hz, 1 H, Ar-H), 7.06 (d, J = 8.3 Hz, 2 H, Ar-H), 6.88 (d,
temperature and quenched with saturated aqueous Na2S2O3 J = 8.3 Hz, 2 H, Ar-H), 6.74 (d, J = 8.3 Hz, 2 H, Ar-H), 5.44 (s, 1
(5 mL). The layers were separated and the aqueous phase was ex- H, Ar-OH), 4.58 (dd, J = 11.3, 3.0 Hz, 1 H, Ar-CH-O), 3.84–3.65
tracted with CH2Cl2 (2 x 5 mL). The combined organic layers were (m, 2 H, CH-OH, CH-O-CH), 3.62 (s, 3 H, CH3O), 2.94–2.33 (m,
washed with brine (3 mL), dried with Na2SO4 and concentrated in 6 H, CH2-CO, CH2-CO, Ar-CH2), 2.40 (s, 3 H, Ar-CH3) ppm. 13
C
Eur. J. Org. Chem. 2010, 345–351
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
349

C. R. Reddy, N. N. Rao, B. Srikanth
FULL PAPER
NMR (75 MHz): δ = 206.1, 154.5, 152.0, 145.1, 140.3, 138.0, 133.2,
130.4, 129.4, 129.1, 128.5, 124.0, 117.6, 115.4, 110.0, 78.1, 78.0,
74.3, 55.6, 49.1, 43.7, 38.6, 29.6, 21.6 ppm. HRMS (ESI): (m/z)
calcd. for C27H32NO8S, 530.1843 [M + NH4]+; found 530.1848.
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4-{(2R,4S,6S)-4-Hydroxy-6-[(S)-1-hydroxy-2-(4-hydroxyphenyl)eth-
yl]tetrahydro-2H-pyran-2-yl}-2-methoxyphenyl 4-Methylbenzenesul-
fonate (16): To
a stirred solution of pyranone 15 (50 mg,
0.097 mmol) in THF (1 mL) at –78 °C was added LS-selectride (1 
in THF, 0.11 mL, 0.11 mmol). After 1 h at –78 °C, the reaction was
quenched with saturated aqueous NH4Cl (1 mL) and warmed to
room temperature. The organic phase was separated and the aque-
ous phase was extracted with ethyl acetate (2ϫ5 mL). The com-
bined organic layers were washed with brine (1 mL), dried with
Na2SO4 and concentrated in vacuo. The crude product was purified
by flash chromatography (70% ethyl acetate in hexanes) to obtain
compound 16 (42 mg. 84%) as a thick liquid. [α]2D7 = +16.3 (c =
1.0, CHCl ). IR (KBr): ν
= 3452, 2923, 2852, 1638, 1512, 1461,
˜
3
max
[2]
1369, 1151, 1090, 865, 771, 719 cm–1. 1H NMR (300 MHz, CDCl3):
δ = 7.76 (d, J = 8.3 Hz, 2 H, Ar-H), 7.30 (d, J = 8.1 Hz, 2 H, Ar-
H), 7.09–7.01 (m, 3 H, Ar-H), 6.83 (d, J = 8.1 Hz, 2 H, Ar-H),
6.69 (d, J = 8.3 Hz, 2 H, Ar-H), 4.80 (d, J = 11 Hz, 1 H, Ar-CH-
O), 4.36 (t, J = 3.0 Hz, 1 H, CH-OH), 3.96–3.81 (m, 1 H, CH-O-
CH), 3.70 (dd, J = 12.0, 5.0 Hz, 1 H, CH-OH), 3.56 (s, 3 H, OCH3),
2.84 (dd, J = 14.0, 5.0 Hz, 1 H, Ar-CH2), 2.72 (dd, J = 14.0, 7.5 Hz,
1 H, Ar-CH2), 2.44 (s, 3 H, Ar-CH3), 1.95–1.60 (m, 4 H, CH2-CH-
OH, CH2-CH-OH) ppm. 13C NMR (75 MHz): δ = 154.4, 151.6,
145.0, 142.8, 137.2, 133.1, 130.3, 129.6, 129.3, 128.4, 123.6, 117.7,
115.3, 110.2, 75.0, 73.6, 73.1, 64.4, 55.5, 40.2, 38.4, 29.6, 21.6 ppm.
HRMS (ESI): (m/z) calcd. for C27H30O8NaS, 537.1559 [M +
Na]+; found 537.1577.
Rhoiptelol (1): To a solution of compound 16 (30 mg, 0.058 mmol)
in MeOH (2 mL) was added K2CO3 (40 mg, 0.29 mmol) and the
mixture was heated at reflux for 2 h. The reaction mixture was co-
oled to 0 °C and acidified with 1  HCl until pH of the solution
reached to 2. The combined aqueous/MeOH solution was extracted
with ethyl acetate (2ϫ5 mL). The organic extracts were washed
with brine (1 mL), dried with Na2SO4, filtered, and concentrated in
vacuo. Purification of crude compound by column chromatography
(70% ethyl acetate in hexanes) provided rhoiptelol 1 (16 mg, 78%)
as a white amorphous powder; m.p. 68–70 °C. [α]2D8 = +77.2 (c =
0.2, MeOH) [ref.[6] [α]1D2 = +97.0 (c = 0.3, MeOH), ref.[7] [α]2D3
=
+97.0 (c = 0.3, MeOH)]. IR (KBr): νmax = 3450, 2922, 1638,
˜
[3]
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a) X. Tian, J. J. Jaber, S. D. Rychnovsky, J. Org. Chem. 2006,
71, 3176–3183; b) W. Takuya, N. Hisanori, A. Masahiro, H.
Shunichi, Tetrahedron: Asymmetry 2007, 18, 2606–2612.
1515 cm–1. 1H NMR (300 MHz, CD3OD): δ = 7.04 (br. s, 1 H, Ar-
H), 7.03 (d, J = 8.1 Hz, 2 H, Ar-H), 6.83 (dd, J = 8.1, 1.9 Hz, 1
H, Ar-H), 6.76 (d, J = 8.1 Hz, 1 H, Ar-H), 6.68 (d, J = 8.1 Hz, 2
H, Ar-H), 4.69 (dd, J = 11.1, 3.0 Hz, 1 H, Ar-CH-O), 4.27 (t, J =
3.0 Hz, 1 H, CH-OH), 3.87 (s, 3 H, OCH3), 3.81 (dt, J = 12.5,
2.8 Hz, 1 H, CH-O-CH), 3.59 (dt, J = 7.0, 3.2 Hz, 1 H, CH-OH),
2.89 (dd, J = 13.4, 6.8 Hz, 1 H, Ar-CH2), 2.69 (dd, J = 13.4, 7.3 Hz,
1 H, Ar-CH2), 1.92 (dd, J = 13.5, 3.0 Hz, 1 H, CH2-CH-OH), 1.83
(dd, J = 14.5, 2.6 Hz, 1 H, CH2-CH-OH), 1.74 (ddd, J = 13.9, 11.3,
3.0 Hz, 1 H, CH2-CH-OH), 1.55 (dd, J = 13.4, 2.0 Hz, 1 H, CH2-
CH-OH) ppm. 13C NMR (75 MHz): δ = 156.7, 148.8, 146.8, 136.2,
131.5, 131.4, 131.2, 119.8, 116.0, 115.9, 115.8, 111.1, 76.4, 75.2,
74.3, 65.7, 56.4, 41.3, 39.7, 35.0 ppm. HRMS (ESI): (m/z) calcd.
for C20H24O6Na, 383.1470 [M + Na]+; found 383.1461.
a) G. Sabitha, P. Padmaja, J. S. Yadav, Helv. Chim. Acta 2008,
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[5]
[6]
[7]
[8]
Acknowledgments
N. N. R. and B. S. thank the Council of Scientific and Industrial
Research (CSIR), New Delhi for research fellowships.
W. Y. Jin, X. F. Cai, M. Na, J. J. Lee, K. Bae, Biol. Pharm. Bull.
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350
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 345–351

Total Synthesis of a Diarylheptanoid, Rhoiptelol B
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[10] Enantiomeric excess (ee) of homoallylic alcohol 8 was deter-
mined by chiral HPLC [Eurocel01, 250ϫ4.6 mm, 5 micron, iPr-
OH/hexanes (15:85), flow rate 1.0 mL/min, retention time 9.51
(7.52%), 10.87 (92.47%)].
[11] D. G. Vassao, D. R. Gang, T. Koeduka, B. Jackson, E. Picher-
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[18] Enantiomeric excess (ee) of compound 4 was determined by
chiral HPLC [chiral IA, 250ϫ4.6 mm, 5 µ, 5% iPrOH in hex-
anes, flow rate 1.0 mL/min, retention time 8.53 (4.07%), 9.17
(95.93%)].
[19] Compound 13 completely existed in enol form and the enoli-
zation may occur from either of the ketone.
[20] a) J. S. Crossman, M. V. Perkins, J. Org. Chem. 2006, 71, 117–
124; b) W. R. Roush, T. D. Bannister, M. D. Wendt, J. A. Jab-
lonowski, K. A. Scheidt, J. Org. Chem. 2002, 67, 4275–4283.
[21] H. Wang, B. J. Shuhler, M. Xian, J. Org. Chem. 2007, 72, 4280–
4283.
[22] There is no over reduction (ring opening at benzylic position)
observed during the conversion of 14 to 15, this may be due to
the presence of tosyl group.
[23] a) W. Peter, T. R. Jonathan, Chem. Commun. 2002, 2066–2067;
b) S. D. Rychnovsky, J. K. David, J. Am. Chem. Soc. 2001, 123,
8420–8421.
[24] The nOe effect between H-1 and H-5 confirmed the cis relation
and absence of effect between H-1/H-5 and H-3 confirmed the
trans relation in structure 16.
[13] L. A. Paquette, J. Chang, Z. Liu, J. Org. Chem. 2004, 69, 6441–
6448.
[14] Enantiomeric excess (ee) of allylic alcohol 11 was, determined
by chiral HPLC [chiral IA, 250x4.6 mm, 5 µ, 5% iPrOH in
hexanes (0.1% diethylamine), flow rate 1.0 mL/min, retention
time 12.70 (5.01%), 13.62 (94.99%)].
[15] L. Alcaraz, J. J. Harnett, C. Mioskowski, J. P. Martel, T.
Le Gall, D.-S. Shin, J. R. Falck, Tetrahedron Lett. 1994, 35,
5449–5452.
[16] The standard wacker oxidation reaction conditions (PdCl2,
CuCl2, O2, and DMF) gave the inseparable mixture of ketone
and aldehyde as shown below. Therefore the modified pro-
cedure was adopted (ref.[17]).
[17] a) G. T. Rodeheaver, D. F. Hunt, J. Chem. Soc., Chem. Com-
mun. 1971, 818–819; b) K. C. Nicolaou, J. Y. Xu, S. Kim, J.
Received: September 10, 2009
Published Online: November 27, 2009
Eur. J. Org. Chem. 2010, 345–351
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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