Total synthesis of Daphnodorin A

Article abstract of DOI:10.1016/j.tet.2014.10.010

A total synthesis of Daphnodorin A, a member of the Daphnodorins, was accomplished. Key features of the synthetic strategy include construction of 2-substituted-3-functionalized benzofuran via intramolecular Heck reaction and a mild Barton-McCombie deoxyg

Full text of DOI:10.1016/j.tet.2014.10.010

Tetrahedron 70 (2014) 9084e9092
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Total synthesis of Daphnodorin A
,
b
,
,
,
Hu Yuan a y, Kaijian Bi a y, Wanlin Chang a y, Rongcai Yue a, Bo Li a, Ji Ye a,
Qingyan Sun a , Huizi Jin , Lei Shan , Weidong Zhang
,
b
a,
a,
*
*
*
a Department of Phytochemistry, School of Pharmacy, Second Military Medical University, Shanghai 200433, China
b School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 14 July 2014
Received in revised form 22 September 2014
Accepted 4 October 2014
Available online 13 October 2014
A total synthesis of Daphnodorin A, a member of the Daphnodorins, was accomplished. Key features of
the synthetic strategy include construction of 2-substituted-3-functionalized benzofuran via intra-
molecular Heck reaction and a mild BartoneMcCombie deoxygenation process mediated by trie-
thylborane. The total synthesis provided Daphnodorin A in 19.7% or 5.6% overall yield over 7 or 15 steps.
Ó 2014 Elsevier Ltd. All rights reserved.
Keywords:
Daphnodorin A
Total synthesis
2,3-Functionalized benzofuran
Intramolecular Heck reaction
BartoneMcCombie deoxygenation
1. Introduction
The biflavonoid Daphnodorin A was originally isolated from the
root of Daphne odora Thunb1 and shown to exhibit notable
biological properties, including
a
-glucosidase inhibitory activity
(3
m
M),2 gastric Hþ, Kþ-ATPase inhibitory activity (4.5
m
M),3
anti-HIV-1 activity,4 antifungal and insecticidal activities,5
12-lipoxygenase and cyclooxygenase inhibitory activities,6 human
chymase-dependent angiotensin II inhibitory activity7 and anti-
tumour properties.8 The Daphnodorins, and the related biflavo-
noids known as the Genkwanols9 and Daphnogirins,10 constitute
the characteristic constituents from Thymelaeaceae, which contain
a 2,3-functionalized benzofuran11 moiety (Fig. 1). Very recently, We
reported an efficient synthetic approach to 2-substituted-3-
functionalized benzofurans that we have applied in the enantio-
selective total synthesis of Daphnodorin B,12 an analogue of
Daphnodorin A bearing a hydroxyl group at C-3 position. We rea-
soned that an enantioenriched flavan-3-ol could be used as
a starting point for a distinct approach toward the synthesis of
Daphnodorin A.
Fig. 1. Selected Daphnodorins and their analogues.
2. Results and discussion
2.1. Synthesis of Daphnodorin A from a known flavan-3-ol
(approach I)
We began our synthetic efforts with flavan-3-ol 2 (Scheme 1),
which was accessed in 47% total yield from 2,4,6-trihydroxy-
acetophenone.12 Deoxygenation of 2 was effected by means of the
Barton protocol,13 yielding the deoxygenated product 3 in the 80%
yield. 8-Iodo derivative 4 was readily prepared in 99% yield by
* Corresponding authors. Tel.: þ86 21 81871245; fax: þ86 21 81871244 (Q.S.);
tel./fax: þ86 21 81871246 (L.S.); tel./fax: þ86 21 81871244 (W.Z.); e-mail addresses:
sqy_2000@163.com, 373668567@qq.com (Q. Sun), shanleicn@126.com (L. Shan),
wdzhangy@hotmail.com (W. Zhang).
y
These authors contributed equally to this work.
http://dx.doi.org/10.1016/j.tet.2014.10.010
0040-4020/Ó 2014 Elsevier Ltd. All rights reserved.

H. Yuan et al. / Tetrahedron 70 (2014) 9084e9092
9085
Scheme 1. Synthesis of Daphnodorin A (approach I).
reacting 3 with 1 equiv of recrystallized NIS14 in DMF. Deprotection
of methoxymethyl (MOM) ether with 3 M HCl afforded o-iodophe-
nol 5, which underwent conjugate addition and subsequent intra-
molecular Heck reaction with ynones (7a and 7b) to generate the
fully protected Daphnodorin A (6a and 6b). Deprotection of 6b with
1 M BBr3 furnished Daphnodorin A whose spectral data were in
complete agreement with those reported in literature2,15 except
Scheme 2. Synthesis of iodophenol 18.
deprotection of MOM ether. Exposure of 20 to HOAc, TFA, NbCl5,19 or
ZnBr2 resulted in deprotection of PMB ether and benzyl ether
(Table 1, entry 1e4). The MOM ether was successfully cleaved by HCl,
along with iodide eliminated byproduct (Table 1, entry 5e7). After
varying other parameters, we were delighted to find that treatment
of 20 with 3 M HCl in MeOH and THF at 40 ꢁC under Ar (in dark)
furnished the desired o-iodophenol 21 in 85% yield (Table 1, entry 8).
20
20
20
optical rotation data ([
a
]
ꢀ6.6 (c 0.6, MeOH); lit.16 value [
a]
D
D
ꢀ59.2 (c 1.14, MeOH)), which indicated that a racemization occurred
under the reaction conditions. We speculate that flavan with a single
chiral centre may be prone to epimerization under harsh conditions.
20
Actually, 4, which exhibited an [
a
]
of ꢀ59.6 (c 0.37, CH3CN)
D
was heated to 75 ꢁC in MeOH for 4 h gave an [
a
]
20 of only ꢀ39.6 (c
D
Table 1
0.3, CH3CN). The ee value was 83% for compound 5, 9% for com-
pound 6a, and 6.5% for compound 6b, respectively. These finding
disqualified 3 as an intermediate in a controlled Daphnodorin A
synthesis and prompted us to turn to the route eliminating the 3-
OH in a late stage and employing benzyl as the protecting group
for phenolic hydroxyls.
Deprotection of intermediate 20
Entry
Deprotection conditions
Yield/%a
1
2
3
4
5
6
7
8
HOAc/THF/i-PrOH, 50 ꢁC
0
2.2. Synthesis of Daphnodorin A (approach II)
TFA/DCM, 0e20 ꢁC
0b
NbCl5/CH3CN, 20 ꢁC
0b
ZnBr2, EtSH/DCM, 0e20 ꢁC
1 M HCl/MeOH/THF¼1:1:1, 60 ꢁC
1 M HCl/i-PrOH/THF¼1:1:1, 50 ꢁC
3 M HCl/MeOH/THF¼1:1:1, 40 ꢁC
3 M HCl/MeOH/THF¼1:1:2, 40 ꢁC/Ar, dark
0c
As illustrated in Scheme 2, the route started by a benzylation
of 2,4-dimethoxymethyl 6-hydroxy phenylacetone 8, followed by
deprotection of the MOM group at the ortho position and con-
densation with 4-(benzyloxy) benzaldehyde to give the chalcone
10 in 95% yield. Decarbonylation of 10 using an improved
methodology of Minami’s method we reported17 provided the
excellent 1,2-reduction selectivity and yield of 11. The phenol
was protected as the TBDMS ether and then subjected to asym-
20(35d)
33(30d)
43(12d)
85
a
Isolated yield.
b
c
PMB was removed.
PMB and Bn were removed.
PMB and iodide were removed.
d
metric dihydroxylation with AD-mix-a, affording the TBS pro-
tected diol 13 in 60% yield (35% starting material was recovered)
and 90.8% ee. De-silylation of and subsequent cyclization under
the orthoformate/acidic conditions18 followed by base hydrolysis
of the formate ester gave the protected flavan-3-ol 15. 8-Iodo
derivative 16 was readily prepared by reacting 15 with NIS, and
its free hydroxyl group was protected as BartoneMcCombie
precursor xanthate by a NaH/CS2/MeI system. Deprotection of
Synthesis of the ynone fragment 25 commenced with prepara-
tion of 4-(benzyloxy) phenylacetylene 24,21 prepared in three steps
from the known iodophenol 22 (Scheme 3). 24 was transformed to
alkynyl-metal reagents and underwent nucleophilic addition to al-
dehyde, followed by quantitative oxidization to ynone 25 by MnO2.
Compound 21 underwent conjugate addition and subsequent
intramolecular Heck reaction with ynone 25 to generate a fully
protected Daphnodorin B 26, which was treated with DDQ to
remove the PMB group. Subsequent cleavage of the OH group via
MOM ether with
2 M HCl afforded o-iodophenol 18. Un-
fortunately, subsequent conjugate addition and intramolecular
Heck cyclization failed to yield 19, a complex mixture was ob-
tained, which might be attributed to the catalyst deactivation
from sulfur poisoning.
Thus, the free hydroxyl group of 16 was protected by p-methox-
ybenzyl (PMB) ether. Several conditions were examined for selective
Barton-McCombie process22 followed by debenzylation with BCl3
20
furnished Daphnodorin A with an [
a]
of ꢀ6.9 (c 0.5, MeOH). We
D
attributed that to the partial racemization of 28 under the Bar-
toneMcCombie reaction conditions since 27 was found to be op-
tically stable under heating (Scheme 4).

9086
H. Yuan et al. / Tetrahedron 70 (2014) 9084e9092
John L. Wood23 and Doo Ok Jang24 discovered that water and
MeOH could replace toxic metal hydrides as the source of hydrogen
in trialkylborane-mediated variants of the BartoneMcCombie
process. In the event, a triethylborane (Et3B)/air or O2/MeOH or
water system using toluene as the solvent was effective (Table 2,
entry 1e4), while a higher yield was obtained using THF as the
solvent (Table 2, entry 5e7). To our surprise, the transformation
proved fruitful when it was conducted under Ar (Table 2, entry
6e7), which suggests that the liberation of the alkyl radical may
also be resulted from a triethylborane-water complex.
Table 2
Scheme 3. Synthesis of ynone 25.
Reduction of xanthate intermediate
Entry
Deoxygenation conditions
Yield/(34/28, %)c
1
2
3
4
5
6
7
H2OeEt3Beair, toluene, 0 ꢁC, 12 h
H2OeEt3BeO2, toluene, rt, 12 h
45/34
53/47
43/45
46/41
59/55
71/63
88/85
MeOHeEt3BeO2, toluene, rt, 12 h
H2OeMeOHeEt3BeO2, toluene, 0 ꢁC, 12 h
H2OeMeOHeEt3BeO2, THF, 0 ꢁC, 12 h
MeOHeEt3B, THF, rt/Ar, 4 h
H2OeMeOHeEt3B, THF, 0 ꢁC/Ar, 2 h
aNaH, CS2, MeI, DMF, 0 ꢁC to rt.
bBBr3, DCM, ꢀ70 ꢁC to ꢀ5 ꢁC or BCl3, DCM, ꢀ10 ꢁC.
c
Isolated yield.
To prevent the partial racemization, freshly prepared 34 or 35
20
was immediately deprotected by BBr3 or BCl3 to produce 1a ([a]
D
ꢀ26.9 (c 0.13, MeOH)), whose enantioselectivity was improved
from er 1:1 to er 2:1. The result showed that the single chiral centre
of the fully protected Daphnodorin A may be prone to racemization
under the mild conditions. In the future, a higher enantioselectivity
may be obtained in a protecting-group-free synthesis manner.
In conclusion, we have achieved the total synthesis of Daph-
nodorin A in 15 linear steps and 5.6% overall yield (2:1 er) starting
from 2,4-dimethoxymethyl 6-hydroxy phenylacetone or seven
linear steps and 19.7% overall yield (2:1 er) starting from a known
flavan-3-ol 2. Key features of this synthesis include a construction
of 2-substituted-3-functionalized benzofuran via intramolecular
Heck reaction and a mild BartoneMcCombie deoxygenation pro-
cess mediated by triethylborane. Efforts are now focused on the
synthesis and extended biological evaluation of other Daphnodor-
ins. Results will be reported in due course.
Scheme 4. Synthesis of Daphnodorin A (approach II).
2.3. Deoxygenated of xanthates under mild conditions (opti-
mized approach II)
Then we tried to explore a mild and efficient deoxygenation
condition. The enantioenriched 29 was employed to construct
a protected Daphnodorin B 33 (Scheme 5), whose free hydroxyl
group at C-3 was transformed into xanthate. Reduction of the
xanthate by conventional n-Bu3SnH/AIBN system gave the de-
oxygenated product 28 or 34 in less than 30% yield.
3. Experimental section
3.1. General
All reactions were performed in dried tube and monitored by
TLC to ensure the completion of the reaction. Nuclear magnetic
resonance (NMR) spectra were recorded using TMS as the internal
standard in DMSO-d6, CD3OD or CDCl3 with a Bruker BioSpin GmbH
spectrometer at 500 or 600 MHz. When peak multiplicities are
reported, the following abbreviations are used: s¼singlet,
d¼doublet, t¼triplet, m¼multiplet, dd¼doublet of doublets; ESI-
MS was recorded on Agilent 1100 LC/MSD (70 eV) spectrometers.
HRMS was recorded on a Waters Q-Tof micro. Melting points (mp)
were determined by microscope melting point apparatus with ar-
omatic temperature control system (XT4A). Flash column chro-
matography was performed by using silica gel (200e300 mesh). All
Scheme 5. Preparation of 33.

H. Yuan et al. / Tetrahedron 70 (2014) 9084e9092
9087
commercially available reagents were used without purification
unless otherwise indicated and were purchased from standard
chemical suppliers.
eluent); IR (KBr) vmax 3004, 2959, 1714, 1599, 1556, 1423, 1363,
1222, 1114 cmꢀ1; 1H NMR (500 MHz, CDCl3)
6.91 (d, J¼8.5 Hz, 2H), 6.26 (s, 1H), 5.39 (s, 1H), 5.05 (dd, J¼2.5,
10.0 Hz, 1H), 3.80 (br s, 3H), 3.78 (br s, 3H), 2.72e2.58 (m, 2H),
2.24e2.19 (m, 1H), 1.96e1.88 (m, 1H); 13C NMR (125 MHz, CDCl3)
d
7.36 (d, J¼8.5 Hz, 2H),
3.2. Experimental procedures and data of synthetic
intermediates
d
159.4, 159.3, 154.6, 154.0, 133.5, 127.2 (2ꢂC), 114.0 (2ꢂC), 104.4,
90.9, 78.3, 67.1, 55.8, 55.5, 29.5, 19.4; HRMS (ESI): m/z calcd for
C
3.2.1. (S)-5-Methoxy-7-(methoxymethoxy)-2-(4-methoxyphenyl)
chroman (3). To 1.73 g (5.0 mmol) of 2 in 15 mL of DMF was added
all at once 0.25 g (6.4 mmol) of NaH (60% in oil). The mixture was
stirred with a powerful magnetic stirrer at rt (mild exotherm) for
10 min, and then it was immersed in a 10 ꢁC water bath, 0.31 mL
(5.0 mmol) of CS2 was added in 5 min, and stirring at 10 ꢁC was
continued for 10 min. To the resulting yellow to amber suspension
was added 0.32 mL (5.0 mmol) of MeI in 5 min. The reaction mix-
ture was left at rt for 20 min and then dissolved in 40 mL of H2O and
60 mL of EtOAc. The phases were separated, and the aqueous phase
was extracted with 20 mL of EtOAc. The combined organic phases
were washed with H2O (3ꢂ40 mL), dried (MgSO4) and concentrated
to give the crude product. A stirred solution of the crude product in
80 mL of anhydrous toluene was heated to 105 ꢁC under Ar, and
a solution of 1.4 mL (5.1 mmol) of n-Bu3SnH and 0.82 g (5.1 mmol)
of AIBN in 40 mL of anhydrous toluene was slowly added over
a period of 4 h. After stirring at 105 ꢁC for 10 h, the reaction mixture
was cooled and directly chromatographed on SiO2 (1:15 EtOAc/
17H18O4I[MþH]þ: 413.0244, found 413.0254.
3.2.4. General procedure for the cyclization reactions. To a solution
of o-iodophenol (0.25 mmol) and ynone (0.38 mmol) in CH3CN
(2.0 mL) was added K3PO4 (0.25 mmol), and then the reaction
mixture was heated until the reaction reached to completion. After
cooling, the reaction mixture was diluted with water (15 mL), and
extracted with EtOAc (2ꢂ15 mL). The combined organic extracts
were dried (MgSO4), and the solvent was removed in vacuo. The
crude product was purified by flash silica gel column chromatog-
raphy (5:1 PE/EtOAc). A mixture of the conjugate addition in-
termediate (0.25 mmol), Pd(OAc)2 (5.7 mg, 0.025 mmol), PPh3
(13 mg, 0.05 mmol), Ag2CO3 (55 mg, 0.25 mmol), and dry CH3CN
(8.0 mL) was stirred at 115 ꢁC for 15 h under Ar atmosphere. The
reaction mixture was cooled to rt, diluted with water (15 mL), and
extracted with EtOAc (2ꢂ15 mL). The combined organic extracts
were dried (MgSO4), and the solvent was removed under vacuo.
The crude product was chromatographed on silica gel (1:8 EtOAc/
PE) to give the title compound compound as characterization.
petroleum ether(PE)) to yield 1.32 g (80% over two steps) of 3.
20
Colourless glass, mp 101e103 ꢁC; [
a
]
þ5.9 (c 0.31, CH3CN); IR
D
(KBr) vmax 3349, 2996, 2953, 1599, 1556, 1441, 1020, 794 cmꢀ1
NMR (500 MHz, CDCl3)
;
1H
3.2.4.1. (S)-(5-Methoxy-2,8-bis(4-methoxyphenyl)-3,4-dihydro-
d
7.32 (d, J¼8.5 Hz, 2H), 6.89 (dd, J¼2.0,
2H-furo[2,3-h]chromen-9-yl)(2,4,6-trimethoxyphenyl)methanone
20
8.5 Hz, 2H), 6.27 (d, J¼2.0 Hz, 1H), 6.16 (d, J¼2.0 Hz, 1H), 5.11 (s, 2H),
4.90 (dd, J¼2.0, 10.5 Hz, 1H), 3.79 (br s, 3H), 3.78 (br s, 3H), 3.45 (br
s, 3H), 2.77e2.72 (m, 1H), 2.65e2.58 (m, 1H), 2.17e2.12 (m, 1H),
(6a). 55% yield, yellow viscous solid, [
a
]
ꢀ38.8 (c 0.25, CH3CN);
D
9% ee (determined by HPLC on a CHIRALPAKÒ IA column using n-
hexane/isopropanol¼75/25 as eluent); IR (KBr) vmax 3250, 1618,
2.02e1.94 (m, 1H); 13C NMR (125 MHz, CDCl3)
d
159.5, 158.7, 157.0,
1516, 1433, 1066 cmꢀ1 1H NMR (500 MHz, CDCl3)
; d 7.65 (d,
156.6, 134.0, 127.6 (2ꢂC), 114.1 (2ꢂC), 104.8, 96.9, 94.8, 92.7, 77.7,
J¼9.0 Hz, 2H), 7.21 (d, J¼8.5 Hz, 2H), 6.90 (d, J¼8.5 Hz, 2H), 6.82 (d,
J¼9.0 Hz, 2H), 6.73 (s, 1H), 5.97 (s, 2H), 4.99 (dd, J¼2.8, 8.8 Hz, 1H),
3.86 (br s, 3H), 3.80 (br s, 3H), 3.77 (br s, 3H), 3.73 (br s, 3H), 3.49 (br
s, 6H), 2.72e2.66 (m, 1H), 2.60e2.54 (m, 1H), 2.16e2.11 (m, 1H),
56.2, 55.7, 55.5, 29.5, 19.7; HRMS (ESI): m/z calcd for
C
19H23O5[MþH]þ: 331.1540, found 331.1559.
3.2.2. (S)-8-Iodo-5-methoxy-7-(methoxymethoxy)-2-(4-
methoxyphenyl)chroman (4). To a solution of 3 (0.66 g, 2 mmol) in
10 mL of anhydrous DMF was added 0.45 g (2 mmol) of recrystal-
lized NIS at 0 ꢁC. The mixture was stirred overnight, and a solution
of 3 M Na2S2O3 (20 mL) was added. The mixture was extracted with
EtOAc (3ꢂ20 mL). The combined organic layer was washed with
brine (25 mL) and H2O (25 mL). The organic layer was then dried
(MgSO4) and concentrated under reduced pressure. This material
was readily recrystallized from DCM/PE to afford the desired
2.00e1.95 (m, 1H); 13C NMR (125 MHz, CDCl3)
d 188.8, 164.2, 161.6,
161.0, 159.9, 157.4, 154.6, 153.5, 149.8, 134.8, 129.9, 127.8, 124.3,
121.4, 115.0, 114.5, 114.4, 111.8, 106.7, 91.9, 87.0, 77.3, 56.3, 56.2, 55.8,
55.7, 55.9, 30.7, 19.5; HRMS (ESI): m/z calcd for C36H35O9[MþH]þ:
611.2276, found 611.2270.
3.2.4.2. (S)-(5-Methoxy-2,8-bis(4-methoxyphenyl)-3,4-dihydro-
2H-furo[2,3-h]chromen-9-yl)(2,4,6-tris(benzyloxy)phenyl)meth-
20
anone (6b). 51% yield, yellow viscous solid, [
a
]
ꢀ45.3 (c 0.36,
D
product (0.91 g, 99%).
CH3CN); 6.5% ee (determined by HPLC on a CHIRALPAKÒ IA col-
20
White solid, mp 143e145 ꢁC; [
a]
ꢀ59.6 (c 0.37, CH3CN); IR
umn using n-hexane/isopropanol¼75/25 as eluent); IR (KBr) vmax
D
(KBr) vmax 3056, 2936, 1598, 1556, 1436, 1050 cmꢀ1
(500 MHz, CDCl3)
;
1H NMR
3268, 1615, 1528, 1399, 1078, 989 cmꢀ1 1H NMR (500 MHz,
;
d
7.38 (d, J¼8.5 Hz, 2H), 6.90 (d, J¼9.0 Hz, 2H),
CDCl3)
d
7.60 (d, J¼9.0 Hz, 2H), 7.39e7.31 (m, 5H), 7.22e7.16 (m,
6.35 (s, 1H), 5.21 (s, 2H), 5.07 (dd, J¼2.0, 10.0 Hz, 1H), 3.79 (br s, 6H),
5H), 7.06e7.05 (m, 5H), 7.00 (d, J¼8.5 Hz, 2H), 6.73 (d, J¼8.5 Hz,
2H), 6.64 (d, J¼9.0 Hz, 2H), 6.55 (s, 1H), 5.92 (s, 2H), 4.87 (d,
J¼3.0 Hz, 2H), 4.65 (br s, 5H, overlapped), 3.85 (br s, 3H), 3.76 (br
s, 3H), 3.61 (br s, 3H), 2.62e2.58 (m, 2H), 1.98e1.93 (m, 1H),
3.52 (br s, 3H), 2.72e2.59 (m, 2H), 2.25e2.19 (m, 1H), 1.96e1.88 (m,
1H); 13C NMR (125 MHz, CDCl3)
d 159.2, 158.9, 156.0, 154.8, 133.5,
127.1 (2ꢂC), 121.6, 114.0 (2ꢂC), 106.2, 95.6, 91.9, 78.0, 68.7, 56.6,
55.8, 55.4, 29.4, 19.5; HRMS (ESI): m/z calcd for C19H22IO5[MþH]þ:
457.0506, found 457.0515.
1.88e1.81 (m, 1H); 13C NMR (125 MHz, CDCl3)
d 189.1, 161.9, 160.0,
159.8, 158.8, 156.4, 154.2, 153.8, 149.1, 136.8, 136.6, 134.3, 129.7,
128.8, 128.4, 127.7, 127.6, 127.1, 127.0, 123.5, 120.7, 115.1, 113.7,
113.5, 110.9, 105.9, 93.1, 86.4, 76.7, 70.4, 70.1, 55.9, 55.5, 55.4, 29.5,
18.9; HRMS (ESI): m/z calcd for C54H47O9[MþH]þ: 839.3215,
found 839.3219.
3.2.3. (S)-8-Iodo-5-methoxy-2-(4-methoxyphenyl)chroman-7-ol
(5). A solution of 4 (456 mg, 1 mmol) in 20 mL MeOH was added
3 M HCl (3 mL) and stirred at 55 ꢁC for 3 h. The reaction was
quenched by the addition of water and extracted with EtOAc
(3ꢂ120 mL). The organic layer was washed with brine, dried over
Na2SO4, and concentrated. The residue was purified on a silica gel
column chromatography (5:1 PE/EtOAc) to afford 5 (371 mg, 90%).
Colourless solid, mp 123e124 ꢁC; 83% ee (determined by HPLC
on a CHIRALPAKÒ IA column using n-hexane/isopropanol¼85/15 as
3.2.5. 1-(2-(Benzyloxy)-6-hydroxy-4-(methoxymethoxy)phenyl)
ethan-1-one (9).25 To a mixture of 2,4-bis(methoxymethoxy)-6-
hydroxy phenylacetone (5.12 g, 20 mmol) and anhydrous potas-
sium carbonate (2.8 g, 21 mmol) in dry acetone (100 mL) was added
BnBr (3.4 g, 20 mmol) at rt. After stirring at rt for 10 min, TBAB

9088
H. Yuan et al. / Tetrahedron 70 (2014) 9084e9092
(2.3 g, 7 mmol) was added, and the resulting mixture was stirred at
rt for 20 h. The resulting mixture was quenched by addition of
water (200 mL) at 0 ꢁC and the aqueous layer was extracted with
EtOAc (3ꢂ250 mL). The combined organic layers were dried over
Na2SO4 and concentrated to furnish a white residue, which was
added to a solution of MeOH (100 mL) and 1 M HCl (5.0 mL) at rt.
After stirring at 30 ꢁC for 12 h, the resulting mixture was cooled to
room temperature, filtered and washed with MeOH (100 mL) to
afford 9 (5.4 g, 90%) as a white solid.
3.2.8. (E)-(3-(Benzyloxy)-2-(3-(4-(benzyloxy)phenyl)allyl)-5-(me-
thoxymethoxy)phenoxy)(tert-butyl)dimethylsilane (12). The pro-
pene 11 (2.41 g, 5.0 mmol) was dissolved in dry DMF (20 mL), and to
this solution were added imidazole (0.38 g, 6.0 mmol) and TBSCl
(0.9 g, 6 mmol) successively at 0 ꢁC. The resulting mixture was
stirred at rt overnight, and then saturated Na2CO3 solution was
added to quench the reaction. The mixture was extracted with
EtOAc. The organic layers were combined, washed with brine, dried
over MgSO4, and evaporated. The residue was purified by flash
chromatograph on silica gel (10/1 PE/EtOAc) to afford 12 (2.95 g,
99%) as an oil.
1H NMR (500 MHz, CDCl3)
1H), 6.13 (d, J¼2.0 Hz, 1H), 5.17 (s, 2H), 5.08 (s, 2H), 3.47 (br s, 3H),
2.55 (br s, 3H); 13C NMR (125 MHz, CDCl3)
204.4, 168.1, 164.5,
d
7.43e7.36 (m, 5H), 6.23 (d, J¼2.0 Hz,
d
IR (KBr) vmax 3000, 2900, 2840, 1633, 1515, 1456, 1397 cmꢀ1; 1H
163.1, 136.6, 129.7, 129.5, 129.0, 107.8, 97.6, 95.0, 93.4, 72.1, 57.4,
NMR (500 MHz, CDCl3)
d
7.43e7.30 (m, 12H), 7.24 (d, J¼9.0 Hz, 2H),
34.4; ESI-MS: m/z 325.1 [MþNa]þ.
6.89 (d, J¼8.5 Hz, 2H), 6.36 (d, J¼2.0 Hz, 1H), 6.29 (d, J¼16.0 Hz, 1H),
6.28 (d, J¼2.0 Hz, 1H), 6.21e6.15 (m, 1H), 5.12 (s, 2H), 5.05 (s, 4H),
3.51 (d, J¼6.0 Hz, 2H), 3.48 (br s, 3H), 1.04 (br s, 9H), 0.28 (br s, 6H);
3.2.6. (E)-1-(2-(Benzyloxy)-6-hydroxy-4-(methoxymethoxy)phenyl)-
3-(4-(benzyloxy)phenyl)prop-2-en-1-one (10). To a suspension of
NaH (1.05 g, 25 mmol, 60% dispersion in oil) in dry DMF (30 mL)
was slowly added 9 (3.02 g, 10 mmol). The resulting mixture was
stirred at this temperature for 15 min. A solution of 4-(benzyloxy)
benzaldehyde (2.12 g, 10 mmol) in DMF (20 mL) was added over
a period of 10 min to the reaction mixture via an addition funnel.
The resulting red-brown solution was stirred at this temperature
for an additional 30 min before stirring at rt for 10 h. The reaction
mixture was quenched with H2O (50 mL) and diluted with EtOAc
(500 mL). The organic layer was separated, washed with H2O
(50 mL), satd NaHCO3 (2ꢂ50 mL), brine (100 mL), dried over
Na2SO4, filtered and concentrated in vacuo to afford a yellow solid.
The solid was triturated with heptane (80 mL) at rt for 1 h and
filtered to produce 10 (4.71 g, 95%) as a yellow solid.
13C NMR (125 MHz, CDCl3)
d 158.3, 157.7, 156.6, 154.7, 137.3, 137.1,
131.3, 128.9, 128.5, 128.5, 127.9, 127.7, 127.5, 127.4, 127.3, 127.0, 114.8,
113.3,100.1, 94.8, 94.7, 70.1, 70.0, 55.9, 26.9, 25.9,18.3, ꢀ4.1; ESI-MS:
m/z 619.1 [MþNa]þ; HRMS (ESI): m/z calcd for C37H45O5Si[MþH]þ:
597.3031, found 597.3035.
3.2.9. (1S,2S)-3-(2-(Benzyloxy)-6-((tert-butyldimethylsilyl)oxy)-4-
(methoxymethoxy)phenyl)-1-(4-(benzyloxy)phenyl)propane-1,2-diol
(13). To a solution containing the TBS ether 12 (1.2 g, 2.0 mmol) in
t-BuOH/H2O (1:1, 40 mL) was added AD-mix-a (2.0 g) in portions.
The heterogeneous mixture was cooled to 0 ꢁC in an ice bath and
methanesulfonamide (0.19 g, 2 mmol) was also added in portions.
The reaction was stirred at 0 ꢁC for 3 days, quenched by addition of
Na2SO3 (1 M, 10 mL) and diluted with EtOAc (60 mL) and H2O
(60 mL). The organic layer was separated and washed with KOH
(2 M, 2ꢂ40 mL), followed by H2O (60 mL). The organic layer was
dried over MgSO4, concentrated under reduced pressure and the
residue was purified by flash chromatography on a silica gel col-
umn (1/3 EtOAc/PE) to afford TBS-protected diol 13 (1.14 g, 90%) as
an oil.
1H NMR (500 MHz, CDCl3)
7.50e7.33 (m, 10H), 7.00 (d, J¼8.0 Hz, 2H), 6.77 (d, J¼8.0 Hz, 1H),
6.29 (s, 1H), 6.20 (s, 1H), 5.21 (s, 2H), 5.08 (s, 4H), 3.50 (br s, 3H); 13
NMR (125 MHz, CDCl3) 193.8, 169.3, 164.5, 162.8, 161.3, 143.8,
d
7.74 (dd, J¼16.5, 41.5 Hz, 2H),
C
d
137.6, 136.5, 131.2, 129.9, 129.8, 129.7, 129.6, 129.3, 129.2, 128.47,
126.3, 116.0, 107.869, 98.0, 95.1, 93.465, 72.4, 71.1, 57.5; ESI-MS: m/z
519.1 [MþNa]þ.
[
a
]
D
20 þ7.5 (c 0.8, CH3CN); IR (KBr) vmax 3508, 2926, 2850, 1586,
1028, 827, 776 cmꢀ1
;
1H NMR (500 MHz, CDCl3)
d
7.44e7.31 (m,
3.2.7. (E)-3-(Benzyloxy)-2-(3-(4-(benzyloxy)phenyl)allyl)-5-(me-
thoxymethoxy)phenol (11). Ethyl chloroformate (1.2 g, 11.0 mmol)
in THF (10 mL) was slowly added at 0 ꢁC to a solution of TEA (1.1 g,
11.0 mmol) and the chalcone 10 (4.96 g, 10 mmol) in THF (20 mL)
over 3 min. The resulting mixture was then stirred at the same
temperature for 30 min. The insoluble amine salt was filtered, the
filter cake washed with an additional volume of THF (20 mL). The
filtrate was added to a vigorously stirred solution of CeCl3$7H2O
(4.1 g, 11.0 mmol) in EtOH (50 mL) and stirred at rt for 30 min.
NaBH4 (910 mg, 24.0 mmol) in EtOH (30 mL) was slowly added to
the mixture (30 min) at ꢀ10 ꢁC. The mixture was allowed to react
for another 45 min, diluted with H2O, cooled, acidified/neutralized
(to pH 3.0e4.0) with dilute HCl, and extracted with DCM (3 por-
tions). The combined DCM extracts were washed in turn with H2O
and brine, dried over MgSO4, filtered, and concentrated
under vacuum, which was further purified by column chromatog-
raphy (1:6 EtOAc/PE) to give the product 11 as a white solid (4.2 g,
88%).
10H), 7.25 (d, J¼8.5 Hz, 2H, overlapped with the peak of CDCl3), 6.89
(d, J¼9.0 Hz, 2H), 6.36 (d, J¼2.0 Hz, 1H), 6.29 (d, J¼2.0 Hz, 1H), 5.10
(s, 2H), 5.04 (s, 2H), 4.99 (s, 2H), 4.42 (d, J¼5.5 Hz, 1H), 3.88e3.85
(m, 1H), 3.46 (br s, 3H), 2.85e2.76 (m, 2H), 0.97 (br s, 9H), 0.22 (br s,
6H); 13C NMR (125 MHz, CDCl3)
d 158.3, 157.0, 155.2, 137.1, 136.5,
133.5, 128.7, 128.6, 128.1, 128.0, 127.9, 127.4, 114.7, 110.7, 100.5, 94.9,
94.7, 76.9, 75.6, 70.5, 70.0, 55.9, 27.6, 25.8, 18.3, ꢀ4.0, ꢀ4.2; ESI-MS:
m/z 653.3 [MþNa]þ; HRMS (ESI): m/z calcd for C37H47O7Si[MþH]þ:
631.3086, found 631.3079.
3.2.10. (1S,2S)-3-(2-(Benzyloxy)-6-hydroxy-4-(methoxymethoxy)
phenyl)-1-(4-(benzyloxy)phenyl)propane-1,2-diol (14). To a solution
of TBS-protected diol 13 (0.63 g, 1 mmol) in anhydrous THF (20 mL)
was added TBAF (0.32 g, 1.0 mmol). The reaction mixture was
stirred at rt for 1.5 h. After complete conversion (monitored by TLC),
the reaction mixture was quenched by addition of satd aq NaHCO3
(20 mL). The reaction mixture was diluted with H2O (50 mL) and
extracted with EtOAc (3ꢂ30 mL). The combined organic layer was
washed with brine (25 mL) and H2O (25 mL). The organic layer was
then dried over MgSO4 and concentrated under reduced pressure
to obtain a brown residue, which was purified by flash chroma-
tography on a silica gel column (1/2 EtOAc/PE) to obtain the triol 14
Mp 81e83 ꢁC; IR (KBr) vmax 3310, 3000, 2961, 2883, 2831, 1628,
1508, 1466, 1401 cmꢀ1 1H NMR (500 MHz, CDCl3)
; d 7.43e7.30 (m,
12H), 7.24 (d, J¼9.0 Hz, 2H), 6.88 (d, J¼9.0 Hz, 2H), 6.42 (d,
J¼16.0 Hz, 1H), 6.32 (d, J¼2.0 Hz, 1H), 6.26 (d, J¼2.0 Hz, 1H),
6.20e6.14 (m, 1H), 5.12 (s, 2H), 5.05 (s, 4H), 3.56 (dd, J¼1.5, 6.5 Hz,
(0.51 g, 99%) as a colourless oil.
2H), 3.47 (br s, 3H); 13C NMR (125 MHz, CDCl3)
d
158.0, 157.8, 157.1,
[
a
]
D
þ7.2 (c 0.4, CH3CN); IR (KBr) vmax 3497, 3266, 2933, 2841,
20
155.7, 137.1, 137.0, 130.4, 130.0, 128.7, 128.6, 128.5, 127.9, 127.8, 127.4,
127.3, 127.3, 126.2, 115.0, 114.9, 108.2, 96.9, 94.6, 94.5, 70.4, 70.0,
56.0, 26.4; ESI-MS: m/z 505.2 [MþNa]þ; HRMS (ESI): m/z calcd for
1576, 1443, 1108, 835, 756 cmꢀ1 1H NMR (500 MHz, CDCl3)
;
d
7.42e7.25 (m, 8H), 7.19 (d, J¼9.0 Hz, 2H), 7.13 (d, J¼9.0 Hz, 2H),
6.83 (d, J¼8.5 Hz, 2H), 6.33 (d, J¼2.0 Hz, 1H), 6.24 (d, J¼2.5 Hz, 1H),
5.11 (s, 2H), 4.95 (s, 2H), 4.86 (dd, J¼12.0, 23.0 Hz, 2H), 4.45 (d,
C
31H31O5[MþH]þ: 483.2166, found 483.2157.

H. Yuan et al. / Tetrahedron 70 (2014) 9084e9092
9089
J¼7.0 Hz, 1H), 4.00e3.96 (m, 1H), 3.46 (br s, 3H), 2.89 (dd, J¼3.5,
14.5 Hz, 1H), 2.70 (dd, J¼3.8, 16.0 Hz, 1H); 13C NMR (125 MHz,
(d, J¼9.0 Hz, 2H), 6.38 (s, 1H), 6.20 (dd, J¼5.0, 8.7 Hz, 1H), 5.57 (d,
J¼4.5 Hz, 1H), 5.45 (s, 1H), 5.04 (s, 2H), 5.00 (s, 2H), 2.95 (dd, J¼4.5,
16.5 Hz, 1H), 2.85 (dd, J¼5.0, 16.5 Hz, 1H), 2.47 (s, 3H); 13C NMR
CDCl3)
d 158.7, 157.8, 157.4, 157.4, 136.9, 136.8, 132.7, 130.9, 128.8,
128.6,128.4, 128.2, 128.0, 127.6, 127.5, 127.08, 114.8, 107.3, 98.0, 94.5,
94.0, 70.1, 69.9, 56.0, 26.5; ESI-MS: m/z 539.1 [MþNa]þ; HRMS
(ESI): m/z calcd for C31H33O7[MþH]þ: 517.2221, found 517.2212.
(125 MHz, CDCl3) d 216.2, 159.7, 159.3, 155.9, 153.3, 137.8, 137.4,
130.6, 129.6, 129.6, 129.0, 129.0, 128.5, 128.2, 128.0, 116.0, 102.2,
93.5, 78.8, 78.4, 67.5, 71.2, 71.0, 23.2, 19.9; ESI-MS: m/z 693.1
[MþNa]þ; HRMS (ESI): m/z calcd for C31H28O5IS2[MþH]þ: 671.0417,
found 671.0427.
3.2.11. (2R,3S)-5-(Benzyloxy)-2-(4-(benzyloxy)phenyl)-7-(methox-
ymethoxy)chroman-3-ol (15). To
a suspension of 14 (0.52 g,
1 mmol) in 1,2-dichloroethane (20 mL) was added triethyl ortho-
formate (1 mL), followed by PPTS (176 mg, 0.7 mmol). The mixture
was stirred at rt for 20 min and then heated to 50 ꢁC for 5 h until
TLC showed the reaction had been completed. After evaporation of
the solvent, the residue was redissolved in 1,2-dichloroethane
(10 mL) and MeOH (10 mL), K2CO3 (200 mg) was added, and the
mixture was stirred at rt overnight. The K2CO3 was filtered and the
filtrate was concentrated under reduced pressure. The residue was
then recrystallized from DCM/PE to afford the desired product 15 as
a white solid (0.41 g, 85% for two steps).
3.2.14. (2R,3S)-5-(Benzyloxy)-2-(4-(benzyloxy)phenyl)-8-iodo-3-
((4-methoxybenzyl)oxy)-7-(methoxymethoxy)chromane (20). 90 mg
of NaH (2.1 mmol, 60% in oil) was added in one portion to a stirred
solution of 16 (0.62 g, 1 mmol) in dry DMF (10 mL) at 0 ꢁC. After gas
evolution had subsided, PMBCl (0.16 g, 1.1 mmol) was added, and
the cooling bath was removed and stirring was continued for 5 h.
The mixture was recooled to 0 ꢁC, whereupon saturated NH4Cl
(10 mL) and H2O (10 mL) were added. The layers were separated,
and the aqueous layer was extracted with EtOAc (3ꢂ10 mL). The
combined organics were washed with H2O and brine, dried
(MgSO4), filtered, and concentrated under reduced pressure. The
residue was purified by flash column chromatography, eluting with
hexanes/EtOAc (6:1) to afford 0.67 g (90%) of the target compound
as a viscous solid.
Mp 144e145 ꢁC; [
a
]
20 þ6.7 (c 0.35, CH3CN); IR (KBr) vmax 3318,
D
2977, 1699, 1578, 1131, 1059 cmꢀ1
;
1H NMR (500 MHz, CDCl3)
d
7.44e7.31 (m, 12H), 7.01 (d, J¼8.5 Hz, 2H), 6.31 (dd, J¼2.5, 9.0 Hz,
2H), 5.11 (s, 2H), 5.08 (s, 2H), 5.04 (dd, J¼11.5, 15.0 Hz, 2H), 4.69 (d,
J¼8.0 Hz, 1H), 4.09e4.05 (m, 1H), 3.46 (br s, 3H), 3.14 (dd, J¼5.5,
11.2 Hz, 1H), 2.68 (dd, J¼4.0, 16.5 Hz, 1H); 13C NMR (125 MHz,
[a
]
20 ꢀ14.3 (c 0.28, CH3CN); IR (KBr) vmax 3010, 2945, 1719, 1601,
D
1543, 1421, 1178, 1033 cmꢀ1; 1H NMR (500 MHz, CDCl3)
d
7.46e7.31
CDCl3)
d
159.1, 157.7, 157.2, 155.4, 136.9, 136.8, 130.1, 128.6, 128.6,
(m, 12H), 7.07 (d, J¼8.5 Hz, 2H), 6.99 (d, J¼8.5 Hz, 2H), 6.80 (d,
J¼8.5 Hz, 2H), 6.47 (s, 1H), 5.21 (s, 2H), 5.09 (s, 2H), 5.05e5.02 (m,
3H, overlapped), 4.29 (dd, J¼11.5, 44.5 Hz, 2H), 3.81e3.75 (m, 1H,
overlapped), 3.78 (br s, 3H), 3.52 (br s, 3H), 2.92 (dd, J¼5.0, 16.5 Hz,
128.5, 128.0, 127.9, 127.4, 127.2, 115.2, 103.3, 96.7, 94.6, 94.3, 81.5,
70.1, 70.0, 68.2, 56.0, 27.8; ESI-MS: m/z 521.1 [MþNa]þ; HRMS (ESI):
m/z calcd for C31H31O6[MþH]þ: 499.2115, found 499.2119.
1H), 2.72 (dd, J¼7.8,16.8 Hz,1H); 13C NMR (125 MHz, CDCl3)
d 159.2,
3.2.12. (2R,3S)-5-(Benzyloxy)-2-(4-(benzyloxy)phenyl)-8-iodo-7-
158.6,157.9,156.1,153.9,137.0,136.7,131.2,130.0,129.4,128.6,128.6,
128.0, 128.0, 127.5, 127.4, 114.7, 113.7, 104.4, 95.4, 93.5, 80.1, 74.1,
71.2, 70.2, 70.0, 68.1, 56.4, 55.3, 25.5. ESI-MS: m/z 767.2 [MþNa]þ;
HRMS (ESI): m/z calcd for C39H38O7I [MþH]þ: 745.1657, found
745.1666.
(methoxymethoxy)chroman-3-ol (16). Compound 16 was prepared
by the same procedure as 4. 91% yield, white solid, mp 171e172 ꢁC;
20
[
a]
þ11.7 (c 0.22, CH3CN); IR (KBr) vmax 3323, 2991, 1718, 1587,
D
1547, 1122, 1066, 988 cmꢀ1; 1H NMR (500 MHz, CDCl3)
d 7.44e7.32
(m,12H), 7.01 (d, J¼9.0 Hz, 2H), 6.49 (s,1H), 5.21 (s, 2H), 5.08 (s, 2H),
5.05 (d, J¼12.0, 16.5 Hz, 2H), 4.87 (d, J¼7.5 Hz, 1H), 4.07e4.03 (m,
1H), 3.52 (br s, 3H), 3.04 (dd, J¼5.5, 16.5 Hz, 1H), 2.72 (dd, J¼8.0,
3.2.15. (2R,3S)-5-(Benzyloxy)-2-(4-(benzyloxy)phenyl)-8-iodo-3-
((4-methoxybenzyl)oxy)chroman-7-ol (21). A solution of 20 (74 mg,
0.1 mmol) in 5 mL MeOH and 10 mL THF was added 3 M HCl (5 mL)
and stirred at 40 ꢁC for 10 h under Ar (in dark). The reaction was
cooled to rt, quenched by the addition of water and extracted with
EtOAc (3ꢂ20 mL). The organic layer was washed with brine, dried
over Na2SO4, and concentrated. The residue was purified on a silica
gel column chromatography (5/1 PE/EtOAc) to afford 21 (60 mg,
85%) as a viscous solid.
16.5 Hz, 1H); 13C NMR (125 MHz, CDCl3)
d 158.9, 158.0, 156.2, 153.8,
136.89, 136.6, 129.9, 128.6, 128.5, 128.1, 128.0, 127.5, 127.3, 115.1,
104.2, 95.4, 93.5, 81.9, 70.2, 70.1, 68.2, 60.4, 56.4, 27.4; ESI-MS: m/z
647.1 [MþNa]þ; HRMS (ESI): m/z calcd for C31H30O6I [MþH]þ:
625.1082, found 625.1080.
3.2.13. O-((2R,3S)-5-(Benzyloxy)-2-(4-(benzyloxy)phenyl)-7-
hydroxy-8-iodochroman-3-yl) S-methyl carbonodithioate (18). To
62 mg (0.1 mmol) of 16 in 3 mL of dry DMF was added 4.5 mg
(0.11 mmol) of NaH (60% in oil). The mixture was stirred with
a powerful magnetic stirrer at rt for 10 min, and then it was im-
[a
]
20 ꢀ21.2 (c 0.58, CH3CN); IR (KBr) vmax 3354, 2921, 1708, 1578,
D
1509, 1255, 1119 cmꢀ1
;
1H NMR (500 MHz, CDCl3)
d
7.48e7.28 (m,
13H), 7.05 (d, J¼8.5 Hz, 2H), 6.98 (d, J¼8.5 Hz, 2H), 6.79 (d, J¼8.5 Hz,
2H), 6.35 (s, 1H), 5.40 (s, 1H), 5.09 (s, 2H), 5.04e5.00 (m, 3H, over-
lapped), 4.29 (dd, J¼11.5, 49.0 Hz, 2H), 3.78 (br s, 3H), 3.78e3.74 (m,
1H, overlapped), 3.77 (br s, 3H), 2.92 (dd, J¼5.0, 16.3 Hz, 1H), 2.74
mersed in a 10 ꢁC water bath, 13
added in 5 min, and stirring at 10 ꢁC was continued for 30 min. To
the resulting yellow to amber suspension was added 13
mL (0.2 mmol) of CS2 was slowly
mL
(dd, J¼8.0, 16.5 Hz, 1H); 13C NMR (125 MHz, CDCl3)
d 159.2, 158.6,
(0.2 mmol) of MeI. The reaction mixture was left at rt for 20 min
and then dissolved in 5 mL of H2O and 6 mL of EtOAc. The phases
were separated, and the aqueous phase was extracted with 10 mL of
EtOAc. The combined organic phases were washed with H2O
(3ꢂ10 mL), dried (MgSO4) and concentrated to give the crude
product. A solution of the crude product in 5 mL MeOH and 5 mL
THF was added 3 M HCl (2 mL) and stirred at 55 ꢁC for 3 h. The
reaction was quenched by the addition of water and extracted with
EtOAc (3ꢂ120 mL). The organic layer was washed with brine, dried
over Na2SO4, and concentrated. The residue was purified on a silica
gel column chromatography (5:1 PE/EtOAc) to afford 18 (54 mg,
80% for two steps) a viscous solid.
158.4,154.6,153.1,136.9,136.7,131.1,130.0,129.4,128.6,128.6,128.0,
128.0,127.5,127.2,114.8,114.7,113.7,102.5, 92.2, 74.1, 71.2, 70.1, 70.0,
66.6, 55.3, 25.3; ESI-MS: m/z 723.2 [MþNa]þ; HRMS (ESI): m/z calcd
for C37H34O6I[MþH]þ: 701.1395, found 701.1399.
3.2.16. ((4-(Benzyloxy)phenyl)ethynyl)trimethylsilane (23). A solu-
tion of 4-iodophenol (6 g, 27.3 mmol), K2CO3(11.3 g, 81.9 mmol) and
BnBr (4.7 g, 27.5 mmol) in acetone (30 mL) was stirred under reflux
for 24 h. Then the reaction mixture was diluted with EtOAc and
washed with 3 M NaOH, dried over Na2SO4, evaporated in low
pressure to give a white solid (8.4 g, 99%). To a solution of this white
solid (7 g, 22.6 mmol), CuI (43 mg, 0.23 mmol), PdCl2(PPh3)2
(159 mg, 0.23 mmol) and trimethylsilylacetylene (4.44 g, 45.2mmol)
in dry THF (50 mL) was added diisoproplamine (6 g, 60 mmol) and
IR (KBr) vmax 2922, 1708, 1566, 1421, 1267, 1098 cmꢀ1
;
1H NMR
(500 MHz, CDCl3)
d
7.42e7.30 (m, 10H), 7.24 (d, J¼9.0 Hz, 2H), 6.94

9090
H. Yuan et al. / Tetrahedron 70 (2014) 9084e9092
the reaction mixture was stirred at rt for 12 h. Then the solution was
filtered off and concentrated under reduced pressure. The crude
product was purified by flash master chromatography (100/1 PE/
EtOAc). A yellow solid product was obtained (6 g, 99%).
3.2.20. ((2R,3S)-5-(Benzyloxy)-2,8-bis(4-(benzyloxy)phenyl)-3-
hydroxy-3,4-dihydro-2H-furo[2,3-h]chromen-9-yl)(2,4,6-
tris(benzyloxy)phenyl)methanone (27). A solution of 26 (12 mg,
0.01 mmol) in 3 mL DCM and 0.3 mL H2O was added DDQ (3 mg,
0.012 mmol) and stirred at rt for 1.5 h. The reaction was quenched
by the addition of saturated aqueous NaHCO3 and extracted with
DCM (2ꢂ10 mL). The organic layer was washed with brine, dried
over Na2SO4, and concentrated. The residue was purified by pre-
Mp 76e77 ꢁC; 1H NMR (500 MHz, CDCl3)
d 7.53e7.35 (m, 7H),
6.85 (d, J¼8.5 Hz, 2H), 5.02 (s, 2H), 0.3 (s, 9H); 13C NMR (125 MHz,
CDCl3)
d
158.5, 138.2 (2ꢂC), 133.4, 128.6 (2ꢂC), 128.0, 127.9(2ꢂC),
117.2 (2ꢂC), 114.6, 105.1, 83.0, 70.0, 0.0.
parative TLC (3/1 PE/EtOAc) to afford 27 (10 mg, 92%).
20
3.2.17. 1-(Benzyloxy)-4-ethynylbenzene (24). A solution of 23 (5.9 g,
21 mmol) and K2CO3 (10.2 g, 73.4 mmol) in dry methanol (30 mL)
and THF (30 mL) was stirred at rt for 12 h. The reaction mixture was
filtered off and the filtrate was evaporated under reduced pressure.
The crude product was dissolved in ethyl acetate and washed with
water. The organic layer was dried over Na2SO4 and evaporated in
vacuum to get a white crystal (4.43 g, 99%).
Yellow amorphous solid, [
a
]
ꢀ19.8 (c 0.45, CH3CN); IR (KBr)
vmax 3318, 2952, 1627, 1605 cmꢀD1; 1H NMR (500 MHz, CDCl3)
d 7.63
(d, J¼8.5 Hz, 2H), 7.48 (d, J¼7.0 Hz, 2H), 7.43e7.31 (m, 18H),
7.21e7.15 (m, 6H), 7.05e7.01 (m, 4H), 6.99 (d, J¼8.5 Hz, 2H), 6.84 (d,
J¼9.0 Hz, 2H), 6.74 (d, J¼8.5 Hz, 2H), 6.69 (s,1H), 5.91 (s, 2H), 5.12 (s,
2H), 5.04 (s, 2H), 4.92 (s, 2H), 4.88 (s, 2H), 4.63 (br s, 4H), 4.45 (d,
J¼6.0 Hz, 1H), 3.93 (dd, J¼1.8, 12.3 Hz, 1H), 2.96 (dd, J¼5.0, 16.5 Hz,
Mp 65e66 ꢁC21; 1H NMR (500 MHz, CDCl3)
d
7.63e7.42 (m, 7H),
1H), 2.74 (dd, J¼7.0, 16.5 Hz,1H); 13C NMR (125 MHz, CDCl3)
d 188.8,
6.95 (d, J¼8.5 Hz, 2H), 5.10 (s, 2H), 3.05 (s, 1H); 13C NMR (125 MHz,
161.9, 159.6, 159.2, 158.4, 155.3, 154.5, 153.7, 147.7, 136.9, 136.9,
136.8, 136.4, 136.3, 130.5, 129.6, 128.7, 128.6, 128.6, 128.3, 128.0,
127.9, 127.8, 127.6, 127.5, 127.59, 127.4, 127.2, 126.9, 123.2, 120.3,
114.7, 114.6, 114.3, 110.5, 104.0, 92.8, 88.3, 80.8, 70.2, 69.9, 69.8, 67.8,
26.8; ESI-MS: m/z 1105.4 [MþNa]þ. HRMS (ESI): m/z calcd for
CDCl3)
d
159.1, 138.7 (2ꢂC), 134.1, 129.1 (2ꢂC), 128.6, 127.9 (2ꢂC),
117.7 (2ꢂC), 115.3, 83.5, 76.3.
3.2.18. 3-(4-(Benzyloxy)phenyl)-1-(2,4,6-tris(benzyloxy)phenyl)
prop-2-yn-1-one (25). To a solution of 24 (1.27 g, 6 mmol) in dry
THF was added vinylmagnesium bromide (3 mL, 2 M in THF solu-
tion) dropwisely at 0 ꢁC under Ar. After being stirred at 40 ꢁC for 1 h,
a solution of 2,4,6-tris(benzyloxy)benzaldehyde (1.31 g, 3 mmol) in
dry THF (1 mL/mmol) was added at 0 ꢁC and stirred continuously at
the same temperature for 1 h. The reaction mixture was quenched
with saturated aqueous NH4Cl at 0 ꢁC and extracted with EtOAc.
The combined organic layers were washed with saturated aqueous
NaHCO3, brine, dried over MgSO4 and filtered. The residue was
purified by flash column chromatography, eluting with PE/EtOAc/
acetone (8:1:1) to afford a crude alcohol. To a solution of the crude
alcohol in dry DCM (1 mL/mmol) was added MnO2 (5.00 equiv) at rt
under Ar. After being stirred at the same temperature for 12 h, the
reaction mixture was filtered thorough a pad of Celite* and the
filtrate was concentrated in vacuo. The target compound was
recrystallized from DCM/PE to afford the desired product 25 as
a yellow solid (0.92 g, 99% for two steps).
C
72H59O10 [MþH]þ: 1083.4103, found 1083.4111.
3.2.21. (S)-(5-(Benzyloxy)-2,8-bis(4-(benzyloxy)phenyl)-3,4-
dihydro-2H-furo[2,3-h]chromen-9-yl)(2,4,6-tris(benzyloxy)phenyl)
methanone (28). Phenyl chlorothionocarbonate (4 mg, 0.012 mmol)
was added to a solution of 27 (22 mg, 0.02 mmol) and pyridine (5 mL)
in DCM (5 mL). After stirring for 6 h at 30 ꢁC, the reaction was
quenched by water and extracted with EtOAc (3ꢂ5 mL). The organic
layers were washed with 1 M HCl, water and saturated Na2CO3 so-
lution, dried over MgSO4, and concentrated to get the crude product,
which was dissolved in 3 mL of anhydrous toluene and heated to
100 ꢁCunderAr. Asolutionofn-Bu3SnH(7.8mg, 0.03mmol)and AIBN
(1.6 mg, 0.01 mmol) in 1 mL of anhydrous toluene was added over
a periodof30min. Afterstirringat100 ꢁC for 1.5h, thecooled reaction
mixture was directly purified by preparative TLC (1/1/8 DCM/EtOAc/
PE) to afford 28 (6 mg, 28%) as a yellow amorphous solid.
IR (KBr) vmax 2959, 1621, 1592 cmꢀ1
CDCl3)
(m, 18H), 7.19e7.14 (m, 6H), 7.06e7.04 (m, 4H), 7.00 (d, J¼8.5 Hz,
2H), 6.81 (d, J¼9.0 Hz, 2H), 6.74 (d, J¼9.0 Hz, 2H), 6.63 (s, 1H),
5.91 (s, 2H), 5.11 (s, 2H), 5.03 (s, 2H), 4.92 (s, 2H), 4.88 (s, 2H),
4.67 (dd, J¼2.0, 8.0 Hz, 1H), 4.62 (dd, J¼12.3, 14.7 Hz, 4H),
2.72e2.69 (m, 2H), 2.01e1.96 (m, 1H), 1.89e1.85 (m, 1H); 13C NMR
;
1H NMR (500 MHz,
7.58 (d, J¼8.5 Hz, 2H), 7.48 (d, J¼7.5 Hz, 2H), 7.42e7.31
Mp101e102 ꢁC;IR(KBr)vmax 1632,1601cmꢀ1;1HNMR (500 MHz,
d
CDCl3)
d
7.44e7.23 (m, 22H), 6.89(d, J¼9.0 Hz, 2H), 6.26(s, 2H), 5.11 (s,
4H), 5.07 (s, 2H), 5.02(s, 2H);13C NMR (125MHz, CDCl3)
d
176.9,162.3,
160.3, 158.9, 136.4, 136.3, 136.2, 134.8, 128.7, 128.7, 128.5, 128.3, 128.2,
127.8, 127.6, 127.5, 127.0, 115.0,113.7, 113.0, 93.5, 90.8, 90.7, 70.6, 70.3,
70.1; ESI-MS: m/z 631.2 [MþH]þ, 653.2 [MþNa]þ; HRMS (ESI): m/z
calcd for C43H35O5[MþH]þ: 631.2479, found 631.2476.
(125 MHz, CDCl3)
d 188.8, 161.7, 159.6, 159.0, 157.8, 155.1, 154.1,
153.4, 149.0, 137.2, 137.1, 136.9, 136.5, 136.4, 134.3, 129.5, 128.7,
128.6, 128.5, 128.2, 128.0, 127.9, 127.8, 127.5, 127.4, 127.3, 127.1,
127.0, 126.9, 123.5, 120.0, 114.4, 114.2, 110.9, 106.1, 92.9, 87.5, 77.2,
76.6, 70.2, 69.9, 69.8, 29.3, 19.0; ESI-MS: m/z 1089.5 [MþNa]þ;
HRMS (ESI): m/z calcd for C72H59O9[MþH]þ: 1067.4154, found
1067.4157.
3.2.19. ((2R,3S)-5-(Benzyloxy)-2,8-bis(4-(benzyloxy)phenyl)-3-((4-
methoxybenzyl)oxy)-3,4-dihydro-2H-furo[2,3-h]chromen-9-
yl)(2,4,6-tris(benzyloxy)phenyl)methanone (26). Compound 26 was
prepared by the same procedure as 6a and 6b.
Yellow viscous solid, [
a
]
20 ꢀ13.5 (c 0.3, CH3CN); IR (KBr) vmax 2931,
D
1621,1596,1423 cmꢀ1; 1H NMR (500 MHz, CDCl3)
d
7.63 (d, J¼8.5 Hz,
2H), 7.46 (d, J¼7.0 Hz, 2H), 7.43e7.29 (m, 18H), 7.19e7.12 (m, 6H),
7.03e7.01 (m, 4H), 6.98 (d, J¼8.5 Hz, 2H), 6.95 (d, J¼9.0 Hz, 2H), 6.84
(d, J¼9.0 Hz, 2H), 6.75 (d, J¼8.5 Hz, 2H), 6.72 (d, J¼8.5 Hz, 2H), 6.64 (s,
1H), 5.91 (s, 2H), 5.11 (s, 2H), 5.04 (s, 2H), 4.92 (s, 2H), 4.84 (dd, J¼11.5,
17.0 Hz, 2H), 4.66e4.59 (m, 5H, overlapped), 4.16 (dd, J¼11.5, 33.5 Hz,
2H), 3.75 (br s, 3H), 3.65 (dd, J¼6.5, 12.0 Hz, 1H), 2.85 (dd, J¼5.0,
16.5 Hz, 1H), 2.78 (dd, J¼6.5,16.5 Hz, 1H); 13C NMR (125 MHz, CDCl3)
3.2.22. (2R,3S)-8-Iodo-5-methoxy-3-((4-methoxybenzyl)oxy)-7-
(methoxymethoxy)-2-(4-methoxyphenyl)chromane (30). Compound
30 was prepared by the same procedure as 20.
20
93% yield, white viscous solid; [
a
]
ꢀ35.1 (c 0.25, CH3CN); IR
D
(KBr) vmax 2941, 1700, 1589, 1549, 1431, 1232, 1092 cmꢀ1; 1H NMR
(500 MHz, CDCl3)
d
7.33 (d, J¼8.5 Hz, 2H), 7.06 (d, J¼9.0 Hz, 2H),
6.91 (d, J¼8.5 Hz, 2H), 6.81 (d, J¼9.0 Hz, 2H), 6.37 (s, 1H), 5.23 (s,
2H), 5.01 (d, J¼7.0 Hz, 1H), 4.30 (dd, J¼11.5, 41.0 Hz, 2H), 3.83 (br s,
3H), 3.81 (br s, 3H), 3.79 (br s, 3H), 3.77e3.73 (m, 1H), 3.54 (br s,
d
188.8, 161.8, 159.7, 159.1, 158.1, 155.1, 154.4, 153.5, 147.9, 137.1, 137.0,
136.9, 136.5, 136.4, 131.8, 130.2, 129.6, 129.2, 128.6, 128.6, 128.2, 127.9,
127.889,127.7,127.6,127.5,127.4,127.2,126.9,123.4,120.4,115.0,114.4,
114.3, 113.6, 110.5, 104.2, 92.8, 88.0, 78.4, 73.8, 70.6, 70.2, 69.9, 69.9,
69.8, 55.2, 24.9; ESI-MS: m/z 1225.4 [MþNa]þ; HRMS (ESI): m/z calcd
for C80H67O11[MþH]þ: 1203.4678, found 1203.4671.
3H), 2.88 (dd, J¼5.0, 16.5 Hz, 1H), 2.69 (dd, J¼7.5, 16.5 Hz, 1H); 13
C
NMR (125 MHz, CDCl3)
d 159.3, 159.2, 158.8, 156.1, 153.8, 130.9,
130.0, 129.3, 128.0, 113.7, 113.7, 103.9, 95.4, 92.0, 80.1, 74.0, 71.0,
67.7, 56.4, 55.6, 55.3, 55.2, 25.3; ESI-MS: m/z 615.1 [MþNa]þ;

H. Yuan et al. / Tetrahedron 70 (2014) 9084e9092
9091
HRMS (ESI): m/z calcd for C27H30O7I[MþH]þ: 593.1031, found
allowed to stir for 5 min. Ar was then bubbled through the solution
for a period of 1 h, at which time, a solution of Et3B (1 mL, 1 M in
THF) in THF was added via a syringe pump over 90 min. After
complete conversion (monitored by TLC), the reaction mixture was
dried over Na2SO4, filtered, and evaporated under reduced pres-
sure. The residue was purified by preparative TLC (7/1/0.03 PE/
593.1018.
3.2.23. (2R,3S)-8-Iodo-5-methoxy-3-((4-methoxybenzyl)oxy)-2-(4-
methoxyphenyl)chroman-7-ol (31). Compound 31 was prepared by
the same procedure as 21.
20
83% yield, white viscous solid; [
a]
ꢀ51.6 (c 0.29, CH3CN); IR
DCM/MeOH) to afford 34 (80 mg, 88%).
D
20
(KBr) vmax 3347, 2941, 1721, 1602, 1522, 1255, 1141, 1033 cmꢀ1
;
1H
7.32 (d, J¼8.5 Hz, 2H), 7.06 (d, J¼8.5 Hz,
Yellow amorphous solid, [
a
]
D
ꢀ54.1 (c 0.50, CH3CN); IR (KBr)
NMR (500 MHz, CDCl3)
d
vmax 2922, 1626, 1427 cmꢀ1 1H NMR (500 MHz, CDCl3)
; d 7.60 (d,
2H), 6.92 (d, J¼8.5 Hz, 2H), 6.81 (d, J¼8.5 Hz, 2H), 6.27 (s, 1H), 4.99
(d, J¼7.5 Hz, 1H), 4.30 (dd, J¼11.5, 44.5 Hz, 2H), 3.83 (br s, 3H), 3.78
(br s, 3H), 3.77 (br s, 3H), 3.80e3.73 (m, 1H, overlapped), 2.89 (dd,
J¼5.5, 16.5 Hz, 1H), 2.69 (dd, J¼8.0, 16.5 Hz, 1H); 13C NMR (125 MHz,
J¼8.5 Hz, 2H), 7.41e7.31 (m, 10H), 7.19e7.16 (m, 6H), 7.06e7.04 (m,
4H), 7.01 (d, J¼8.5 Hz, 2H), 6.81 (d, J¼9.0 Hz, 2H), 6.65 (d, J¼9.0 Hz,
2H), 6.56 (s, 1H), 5.92 (s, 2H), 5.03 (s, 2H), 4.88 (dd, J¼11.5, 13.5 Hz,
2H), 4.67 (d, J¼2.5 Hz, 1H), 4.65 (br s, 4H), 3.86 (br s, 3H), 3.68 (br s,
3H), 2.63e2.59 (m, 2H), 2.01e1.99 (m, 1H), 1.88e1.86 (m, 1H); 13C
CDCl3)
d 159.4, 159.2, 159.1, 154.7, 153.0, 130.8, 130.0, 129.3, 128.0,
113.7, 102.0, 91.1, 80.3, 74.0, 71.0, 66.1, 55.6, 55.3, 55.2, 25.2; ESI-MS:
m/z 571.0 [MþNa]þ; HRMS (ESI): m/z calcd for C25H26O6I[MþH]þ:
549.0769, found 549.0766.
NMR (125 MHz, CDCl3) d 188.8, 161.7, 159.6, 159.0, 158.6, 156.2,
153.6, 148.9, 136.9, 136.5, 136.4, 134.1, 129.5, 128.6, 128.6, 128.2,
128.2,127.9,127.5,127.4,127.4,126.9,126.8,123.5,114.9,114.2,113.4,
110.7, 105.7, 92.9, 86.1, 76.5, 70.2, 69.9, 55.67, 55.1, 29.2, 18.7; ESI-
MS: m/z 937.4 [MþNa]þ; HRMS (ESI): m/z calcd for
3.2.24. ((2R,3S)-8-(4-(Benzyloxy)phenyl)-5-methoxy-3-((4-
methoxybenzyl)oxy)-2-(4-methoxyphenyl)-3,4-dihydro-2H-furo
[2,3-h]chromen-9-yl)(2,4,6-tris(benzyloxy)phenyl)methanone
(32). Compound 32 was prepared by the same procedure as 6a
C
60H51O9[MþH]þ: 915.3528, found 915.3518.
3.2.27. Daphnodorin A (1a). Freshly prepared 34 or 28 (0.05 mmol,
1.0 equiv) was dissolved in dry CH2Cl2 (2 mL), and BBr3 or BCl3
(0.9 mL, 0.9 mmol, 1.0 M in CH2Cl2) was added at ꢀ78 ꢁC. The re-
sultant red-brown solution was warmed to ꢀ10 ꢁC and stirred for
10 h under Ar. Upon completion, the reaction contents were
quenched by the addition of water (2 mL), stirred vigorously for
3 min at 0 ꢁC, and extracted with EtOAc (3ꢂ5 mL). The combined
organic extracts were then washed with water (5 mL) and brine
(5 mL), dried (MgSO4), filtered, and concentrated. The resultant
crude material was purified by preparative TLC (100:10:1 CH2Cl2/
MeOH/AcOH) to give Daphnodorin A as a yellow amorphous
powder (13.4 mg, 51% from 28; 15.8 mg, 60% from 34).
and 6b.
20
58% yield, yellow amorphous solid; [
a
]
ꢀ29.6 (c 0.34,
D
CH3CN); IR (KBr) vmax 2940, 1625, 1596, 1450, 1409 cmꢀ1; 1H NMR
(500 MHz, CDCl3)
7.66 (d, J¼9.0 Hz, 2H), 7.43e7.32 (m, 10H),
d
7.19e7.16 (m, 6H), 7.04e7.02 (m, 4H), 6.98 (d, J¼8.5 Hz, 2H), 6.94
(d, J¼9.0 Hz, 2H), 6.85 (d, J¼9.0 Hz, 2H), 6.75 (d, J¼8.5 Hz, 2H),
6.63 (d, J¼8.5 Hz, 2H), 6.57 (s, 1H), 5.92 (s, 2H), 5.05 (s, 2H), 4.85
(dd, J¼11.5, 20.5 Hz, 2H), 4.62 (br s, 4H), 4.58 (dd, J¼5.5, 11.5 Hz,
1H, overlapped), 4.17 (dd, J¼11.5, 32.0 Hz, 2H), 3.86 (br s, 3H),
3.75 (br s, 3H), 3.68 (br s, 3H), 3.63e3.60 (m, 1H), 2.78 (dd, J¼5.0,
16.5 Hz, 1H), 2.70 (dd, J¼7.0, 16.5 Hz, 1H); 13C NMR (125 MHz,
CDCl3)
d
188.9, 161.7, 159.6, 159.0, 158.8, 156.1, 154.2, 153.6, 147.8,
2:1 er (determined by HPLC on a CHIRALPAKÒ IE column using
n-Hexane/EtOH/MeOH/TFA¼84/12/4/0.1 as eluent); IR (KBr) vmax
136.8, 136.5, 136.4, 131.5, 130.2, 129.5, 129.1, 128.6, 128.5, 128.2,
127.9, 127.6, 127.5, 127.4, 127.3, 126.8, 123.4, 120.4, 115.0, 114.3,
113.6, 113.3, 110.2, 103.6, 92.8, 86.5, 78.3, 73.7, 70.4, 70.2, 69.9,
69.9, 55.7, 55.2, 55.1, 30.9, 24.6; ESI-MS: m/z 1073.5 [MþNa]þ;
HRMS (ESI): m/z calcd for C68H59O11[MþH]þ: 1051.4052, found
1051.4044.
3245, 1623, 1516, 1047 cmꢀ1; 1H NMR (500 MHz, CD3OD)
d 7.45 (d,
J¼9.0 Hz, 2H), 6.88 (d, J¼8.5 Hz, 2H), 6.73 (d, J¼8.5 Hz, 2H), 6.62 (d,
J¼8.5 Hz, 2H), 6.50 (s, 1H), 5.71 (s, 2H), 4.78 (d, J¼10.0 Hz, 1H),
2.79e2.64 (m, 2H), 2.20e2.16 (m, 1H), 1.83e1.75 (m, 1H); 13C NMR
(125 MHz, CD3OD)
d 197.3, 167.8, 158.8, 157.5, 155.1, 154.7, 150.4,
149.5, 134.1, 128.4, 127.7, 123.8, 118.9, 116.6, 116.0, 112.2, 108.1, 106.1,
3.2.25. ((2R,3S)-8-(4-(Benzyloxy)phenyl)-3-hydroxy-5-methoxy-2-
(4-methoxyphenyl)-3,4-dihydro-2H-furo[2,3-h]chromen-9-yl) (2,4,6-
tris(benzyloxy)phenyl)methanone (33). Compound 33 was pre-
pared by the same procedure as 27.
96.0, 90.5, 78.6, 31.3, 21.4; HRMS (ESI): m/z calcd for
C
30H23O9[MþH]þ: 527.1337, found 527.1345.
Acknowledgements
99% yield, yellow amorphous solid, [
a]
20 ꢀ34.5 (c 0.24, CH3CN);
D
IR (KBr) vmax 3333, 2928, 1621, 1425 cmꢀ1
;
1H NMR (500 MHz,
The work was supported by the program NCET Foundation,
NSFC (81230090), Shanghai Leading Academic Discipline Project
(B906), Key Laboratory of Drug Research for Special Environments,
PLA, Shanghai Engineering Research Center for the Preparation of
Bioactive Natural Products (10DZ2251300), the Scientific Founda-
tion of Shanghai China (12401900801, 13401900101), National
Major Project of China (2011ZX09307-002-03), and the National
Key Technology R&D Program of China (2012BAI29B06).
CDCl3)
d
7.66 (d, J¼9.0 Hz, 2H), 7.43e7.32 (m, 10H), 7.22e7.16 (m,
6H), 7.06e7.03 (m, 4H), 6.98 (d, J¼8.5 Hz, 2H), 6.85 (d, J¼9.0 Hz, 2H),
6.65 (d, J¼9.0 Hz, 2H), 6.61 (s, 1H), 5.93 (s, 2H), 5.05 (s, 2H), 4.88 (dd,
J¼11.5, 15.0 Hz, 2H), 4.65 (br s, 4H), 4.45 (d, J¼6.5 Hz,1H), 3.94e3.90
(m, 1H), 3.86 (br s, 3H), 3.68 (br s, 3H), 2.82 (dd, J¼5.5, 16.5 Hz, 1H),
2.70 (dd, J¼6.7, 16.7 Hz, 1H); 13C NMR (125 MHz, CDCl3)
d 188.7,
161.8, 159.5, 159.1, 156.4, 154.3, 153.8, 147.5, 136.8, 136.4, 136.4,
130.3, 129.5, 128.6, 128.6, 128.5, 128.2, 128.1, 128.0, 127.6, 127.5,
126.9, 123.3, 120.3, 114.8, 114.3, 113.7, 110.3, 103.5, 92.8, 86.9, 80.7,
70.2, 69.9, 67.7, 55.7, 55.1, 30.9, 26.3; ESI-MS: m/z 953.4 [MþNa]þ;
HRMS (ESI): m/z calcd for C60H51O10[MþH]þ: 931.3477, found
931.3482.
Supplementary data
1H and 13C NMR spectra of all the new compounds is available
free of charge. Supplementary data related to this article can be
found at http://dx.doi.org/10.1016/j.tet.2014.10.010.
3.2.26. (S)-(8-(4-(Benzyloxy)phenyl)-5-methoxy-2-(4-
methoxyphenyl)-3,4-dihydro-2H-furo[2,3-h]chromen-9-yl)(2,4,6-
tris(benzyloxy)phenyl)methanone (34). The xanthate was prepared
by the same procedure described in Section 3.2.1. To a solution of
the xanthate (102 mg, 0.1 mmol, 1.0 equiv) dissolved in dry THF
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