From the gold-catalysed benzylation of arenes to the regio- and stereoselective synthesis of procyanidins dimers

Article abstract of DOI:10.1016/j.tet.2014.11.011

This work reports on a new intermolecular C-C coupling reaction between electron rich arenes and benzylic alcohols or ethers, catalysed by gold(III) salts, or other catalysts such as gold(I) and iron (III), and its application to the regio- and stereoselective synthesis of procyanidins dimers B1 and B3.

Full text of DOI:10.1016/j.tet.2014.11.011

Tetrahedron 71 (2015) 3045e3051
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
From the gold-catalysed benzylation of arenes to the regio- and
stereoselective synthesis of procyanidins dimers
*
Sandy Fabre, Marie Gueroux, Emeline Nunes, Magali Szlosek-Pinaud, Isabelle Pianet ,
*
Eric Fouquet
ꢀ
ꢀ
ꢀ
Institut des Sciences Moleculaires, Universite de Bordeaux, CNRS, 351, Cours de la Liberation, 33405 Talence cedex, France
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 6 May 2014
Received in revised form 26 September 2014
Accepted 6 November 2014
Available online 15 November 2014
This work reports on a new intermolecular CeC coupling reaction between electron rich arenes and
benzylic alcohols or ethers, catalysed by gold(III) salts, or other catalysts such as gold(I) and iron (III), and
its application to the regio- and stereoselective synthesis of procyanidins dimers B1 and B3.
Ó 2014 Elsevier Ltd. All rights reserved.
Keywords:
Procyanidins
Gold salts
Catalysis
Arenes functionalization
Ether activation
1. Introduction
hydrogenation of alkenes catalysed by gold.4 Consequently, the use
of gold as catalyst has increased in an exponential manner over the
Among the large family of tannins, procyanidins or condensed
tannins are the most abundant species in grapes and wine, in which
they are transferred during wine-making operations. They are
oligomers of flavan-3-ols and are attracting attention for their key
role in wine taste1 as well as for their putative healing properties.2
Their molecular diversity comes from the different monomeric
constituents, the degree of oligomerization as well as the connec-
tivity between the flavan units thus leading to an infinite library of
these compounds. In order to reach the wine composition in olig-
omeric procyanidins, and their role in wine taste, a variety of pure
and structurally determined synthetic standards is required. In
addition to continuous efforts reported in the field,3 new routes
have to be developed to synthesize these compounds, in order to
increase the degree of complexity of the standards available. No-
tably, the yield of the coupling reaction between the two flavan
units has to be optimized by keeping the control of its regio and
stereoselectivity, thus ensuring a stereoselective synthesis of pro-
cyanidins of higher degree of polymerization.
past twenty years for various uses such as hydrogenations, oxida-
tions, reactions with carbon monoxide, nucleophilic additions to
CeC multiple bonds, as well as activation of alcohols and carbonyl
groups.5 Primarily this flourishing chemistry was mainly related to
heterogeneous catalysis, especially due to the exceptional reactivity
of gold nanoparticles.6 Nevertheless, in the last decade the use of
gold salts also increased, mainly due to the robustness of the cat-
alysts and their high reactivity even at low temperature, so that the
homogeneous gold catalysis cannot be ignored anymore both in
organic chemistry7 or in total synthesis developments.8
The functionalization of arenes via direct CeH replacement is
one of the numerous reactions, in which gold catalysis recently
showed its efficiency and represents an attractive way of forming
CeC bonds under mild conditions. Although the first report of an
aryl CeH activation with gold(III) salts goes back to the 30’s,9 this
reaction received far less attention than those involving alkenes or
alkynes. In this context the seminal work of Beller in 2006
reporting the first gold catalysed benzylation of arenes with benzyl
alcohols and carboxylates10 contrasted with the large amount of
inter- or intramolecular FriedeleCrafts type reactions using gold(-
Gold was known for decades for its rich organometallic and
coordination chemistry, but was considered as a poor catalyst until
the early seventies and the pioneering work of Bond on the
III) activated
p systems as partners. In the course of finding new
approaches to achieve CeC couplings with electron rich arenes and
benzylic electrophiles, we became interested in the use of gold salts
for such catalysis under mild conditions, which could be further
applied to the synthesis of more complex molecules.
* Corresponding author. Tel.: þ33 (0)54 000 2829; fax: þ33 (0)54 000 6283;
e-mail address: e.fouquet@ism.u-bordeaux1.fr (E. Fouquet).
http://dx.doi.org/10.1016/j.tet.2014.11.011
0040-4020/Ó 2014 Elsevier Ltd. All rights reserved.

3046
S. Fabre et al. / Tetrahedron 71 (2015) 3045e3051
2. Results and discussion
allowed us to get a total diastereocontrol, when using an excess of
TiCl4 as Lewis acid as shown in a previous work.3f
We first studied the reaction between 1-phenylethanol and 1,3-
dimethoxybenzene or 1,3,5-trimethoxybenzene, catalysed by
gold(III) salts (Scheme 1) as model reaction. The choice of NaAuCl4
as catalyst instead of HAuCl4 was driven by observations in the
nucleophilic substitution of propargylic alcohols showing its re-
activity even at room temperature.11
As expected the use of the 2-hydroxyethyloxy moieties allowed
to recover a total diastereocontrol in the formation of the new
stereogenic carbon. Pleasingly, the use of a benzylic ether as sub-
strate displayed an even better reactivity than the benzylic alcohol
itself furnishing the coupling products 7 in 80% yield. Finally, the
use of 1,3,5-trimethoxybenzene as nucleophile led to the formation
of 8 in an excellent 89% yield, showing that the increase of the
nucleophilic character of the aromatic could easily counterbalance
the relative steric hindrance of the ortho/ortho disubstitution.
Contrastingly to the use of the more oxophilic TiCl4, which required
2 equiv of the Lewis acid for the reaction to proceed, this meth-
odology proceeded under catalytic conditions in gold (5% of
NaAuCl4). Interestingly, there is to date no real example of gold
catalysed arenes substitutions by using benzylic ethers as sub-
strates as the main efforts were focused on more reactive benzylic
alcohols10,11 or epoxides.12
Scheme 1. Coupling of 1-phenylethanol with electron-rich benzenes.
Encouraged by these promising results, we decided to apply our
methodology to the stereocontrolled synthesis of procyanidin B3.
An equimolar amount of tetra-O-benzylcatechin and C4-activated
catechin derivative 6 were mixed in dichloromethane, at room
temperature in the presence of 5% of NaAuCl4 to give exclusively
the octa-O-benzylated dimer 9 in an excellent 80% yield (Scheme
4). As observed with 1,3-dimethoxy- or 1,3,5-trimethoxybenzene
as nucleophiles, the reaction proceeded with a total diastereocon-
trol of the created interflavan bond. Furthermore, it has to be noted
the total regiocontrol of the reaction giving exclusively, as antici-
pated, the C4eC8 interflavan bond. Finally a one step debromina-
tion/debenzylation of 9, catalysed by Pearlman’s catalyst Pd(OH)2/C
in the presence of triethylamine furnished quantitatively procya-
nidin B3 10 with a total regio- and diastereocontrol in only four
steps from tetra-O-benzylcatechin. It is worth noting that a similar
approach for the one-step deprotection has also been recently used
by Suzuki for the first regiocontrolled synthesis of a procyanidin
dimer with a 4,6 interflavan bond.13
The reaction was effective at room temperature, with only 5% of
gold(III) catalyst, giving a 4.5:1 mixture of regioisomers 1 and 2
with a preferential ortho/para orientation. Interestingly, the use of
1,3,5-trimethoxybenzene as substrate led to the formation of the
coupling product 3 in a fair yield of 54% indicating that an ortho/
ortho disubstitution didn’t have a negative effect on the outcome of
the reaction. This result prompted us to apply the reaction to the
tetra-O-methyl-4-hydroxycatechin 4, prepared in two steps from
the commercially available catechin, as the benzylic partner, with
the 1,3-dimethoxybenzene as nucleophile (Scheme 2).
Scheme 2. Coupling of tetra-O-methyl-4-hydroxycatechin with 1,3-dimethoxybenzene.
Under the same conditions, the coupling product 5 resulting
from the ortho/para orientation was isolated in 58% yield, as the
unique regioisomer. This change in reactivity can be explained by
the increase of the steric hindrance of the benzylic alcohol, leading
to a total discrimination between the two possible regioisomers.
Nevertheless, the created stereogenic centre was only obtained
with a poor 1.3:1 diastereoselectivity. This result led us to change
the nature of the substrates, moving from benzylic alcohols to
Scheme 4. Gold(III) catalysed synthesis of procyanidin B3.
benzylic ethers. We then used the tetra-O-benzyl-4b-(2-
hydroxyethyloxy)-8-bromocatechin 6 (Scheme 3), prepared in
three steps from catechin.3a,b Indeed, this bidentate leaving group
The reaction was also extended to epicatechin derivatives to
achieve the stereocontrolled synthesis of procyanidin B1, by using
tetra-O-benzyl-4
b-(2-hydroxyethyloxy)8-bromoepicatechin
11
under the conditions previously defined for procyanidin B3 syn-
thesis. As expected, the reaction occurred with a double inversion
of configuration, affording exclusively the octabenzylated dimer 12
with the natural configuration of the interflavane bond in a non-
optimized 61% yield (Scheme 5).
These results contrast with the abovementioned strat-
egies,3aeg,13 which necessitated an equivalent or even excess
amounts of Lewis acid to proceed. Indeed and contrarily to the
more oxophilic Lewis acids such as TiCl4 or SnCl4, the relative
weakness of the AueO interaction allows the reaction to proceed
Scheme 3. Coupling reaction with tetra-O-benzyl-4ß-(2-hydroxyethyloxy)-8-
bromocatechin.

S. Fabre et al. / Tetrahedron 71 (2015) 3045e3051
3047
noting that FeCl3 could also catalyse the reaction in the same way
with both substrates 6 and 13 (Entries 3 and 6), thus opening the
way to a convenient and inexpensive strategy of procyanidin
synthesis.
3. Conclusions
In this work, we developed a new strategy of creating
aromatic-benzylic CeC bonds, based on the activation of benzylic
ethers with gold(III) salts. The reaction conditions are smooth
enough to be applied to the synthesis of complex molecules such
as procyanidins under real catalytic conditions. Furthermore,
simply by tuning the nature of the substrate we have shown that
the use of gold salts was compatible with control of the stereo-
chemistry of the created interflavan bond, thus giving an easy
access to procyanidin dimers either from catechin or epicatechin
monomers. Finally the extension of the reaction to other catalysts
such as gold(I) or iron(III) holds great promises to authorize fur-
ther extensions of this work.
Scheme 5. Gold(III) catalysed synthesis of procyanidin B1.
smoothly under catalytic conditions. Nevertheless, the 2-
hydroxyethyloxy substituent is acting as a bidentate ligand to-
wards the gold(III) atom, in the same way as previously demon-
strated for TiCl4 mediated reaction.3f It was thus verified that the
stereochemistry outcome of the C4 benzylic carbon was dictated by
the stereochemistry of the adjacent C3 hydroxyl group. Finally, the
same one-step deprotection procedure led quantitatively to the
procyanidin B1 13.
4. Experimental
However, as the stereocontrol of the reaction is still assumed to
be correlated to a bidentate coordination of the gold atom by the
two oxygen atoms of the 2-hydroxyethyloxy moiety, we were in-
terested in the use of the O-propargyl group to check whether an
alkyne/gold coordination would be able to succeed, in the same
way, the diastereocontrol of the reaction. Indeed, this propargyloxy
arm has been already introduced as activating group for the stoi-
chiometric Lewis acid mediated coupling reaction.14 Furthermore,
such bidentate alkynyl/oxygen gold interaction has been already
proposed to explain the peculiar reactivity of propargylic alcohols
All reactions were performed under argon with magnetic stir-
ring and with anhydrous solvents. Catechin was purchased from
Fluka. Pearlman’s catalyst [20% Pd(OH)2/C] was obtained from
Aldrich and contained up to 50% H2O. Column chromatography was
performed using silica gel 60 (0.063e0.200 mm, Merck) or silica gel
40 (0.040e0.060 mm, Merck) for flash chromatography. Melting
points (mp) were determined with a Stuart Scientific SMP3 melting
point apparatus and are uncorrected. Infrared spectra were recor-
ded using a PerkineElmer FTIR Paragon 1000 spectrometer (KBr
disc) and values are reported in cmꢀ1. 1H and 13C NMR spectra were
recorded with either a Bruker Avance DPX 300 or a Bruker Avance
NB 400 spectrometer at room temperature (22 ꢁC). The 1H and 13C
NMR spectra were recorded in CDCl3 for protected compounds and
H2O/D2O (90:10) or D2O/[D6]ethanol (88:12) for deprotected
with gold salts.15 The tetra-O-benzyl-4
b-(2-propargyl) bromoca-
techin 13 was then prepared and submitted to the same reaction
conditions leading to the expected coupling product 9, in 58% yield
with the same regio- and stereoselectivity as observed with 6
(Scheme 6). In that case, the somewhat lower yield obtained when
starting from 13 could be explained by a weaker coordination of the
gold(III) atom with the O-propargyl group than with the 2-
hydroxyethyl moiety.
compounds with TPS as an internal standard. Chemical shifts d and
coupling constants J are given in parts per million and Hertz, re-
spectively. Mass spectra were obtained on a Micromass Autospec-Q
mass spectrophotometer [electron-impact ionization (70 eV) or
LSIMS].
b
4.1. 30,40,5,7-Tetra-O-methyl-4 -hydroxycatechin (4)16
Distilled water (131 l, 7.3 mmol, 3 equiv) and DDQ (1.66 g,
m
3 equiv) were added to a solution of 30,40,5,7-tetra-O-methyl-
catechin (843 mg, 2.43 mmol) in dichloromethane (20 mL) at room
temperature. A purple precipitate appeared instantaneously. After
3 h of stirring at room temperature, DMAP (743 mg, 2.5 equiv) was
added. After an additional 15 min of stirring, the solvent was
evaporated. The resulting crude material was purified by chroma-
tography on silica gel (pentane/ethyl acetate, 3:2) to obtain after
evaporation and drying in vacuo the product 4 as a white solid
(430 mg, 1.12 mmol, 46% yield).
Scheme 6. Synthesis of procyanidin B3 starting from tetra-O-benzyl-4ß-(O-prop-
argyl)-8-bromocatechin.
Finally, we were interested in varying the nature of the catalyst
to extend the scope of the catalysed coupling reaction (Table 1).
Interestingly, the use of a weaker Lewis acid such as gold(I) salts
also led to the coupling, in lower yields when using the 2-
hydroxyethyloxy arm (Entry 1) but with a similar efficiency if us-
ing the propargylic ether as activating group (Entry 4). It is worth
NMR: 1H (300 MHz, CDCl3, ppm)
d
¼7.04 (H60, d, 1H,
0
0
0
0
0
0
J6 ,5 ¼7.9 Hz); 7.01 (H2 , s, 1H); 6.92 (H5 , d, 1H, J5 ,6 ¼7.9 Hz); 6.12
(H6 & H8, s, 2H); 5.04 (H4, d, 1H, J4,3¼4.4 Hz); 4.92 (H2, d, 1H,
J2,3¼10.1 Hz); 3.95 (H3, m, 1H); 3.91 (CH3, s, 3H) 3.90 (CH3, s, 3H)
3.86 (CH3, s, 3H) 3.76 (CH3, s, 3H).
Table 1
Variation of the catalyst for the synthesis of procyanidin B3
Entry
Catalyst (5% equiv)
Electrophile
9 (Yield %)
13C (75 MHz, CDCl3, ppm)
d
¼167.3 (C7); 165.2 (C5); 162.4 (C8a);
1
2
3
4
5
6
AuCl
NaAuCl4
FeCl3
AuCl
NaAuCl4
FeCl3
6
6
6
13
13
13
67
80
62
57
58
74
150.1 (C30); 149.4 (C40); 129.3 (C10); 120.6 (C60); 111.5 (C50); 111.3
(C20); 103.2 (C4a); 93.6 (C8); 92.4 (C6); 83.6 (C2); 72.9 (C3); 62.5
(C4); 56.5 (CH3); 56.3 (CH3); 56.2 (CH3); 56.0 (CH3).
SMHR (m/z): [MþNa]þ¼385.1256 (calculated for C19H22O7Na:
385.1263).

3048
S. Fabre et al. / Tetrahedron 71 (2015) 3045e3051
4.2. 30,40,5,7-Tetra-O-methylcatechin-4
dimethoxybenzene) (5)
a
-(1,3-
SMHR (m/z): [MþNa]þ¼811.1893 (calculated for C45H41BrO8Na:
811.1883).
NaAuCl4$2H2O (0.05 equiv) was added to 30,40,5,7-tetra-O-
methyl-4-hydroxylcatechin 4 (113 mg, 311 mol, 1 equiv) and 1,3-
dimethoxybenzene (81 l, 623 mol, 2 equiv) in dichloromethane
4.4. 30,40,5,7-Tetra-O-benzyl-4
b-(2-hydroxyethyloxy)-8-
bromo-catechin (6)
m
m
m
(3 mL). The solution was stirred at room temperature for 12 h. The
organic layer was washed with brine and the aqueous phases were
extracted with dichloromethane. The organic phases were then
dried with MgSO4. After evaporation of the solvents, the crude
material was purified by chromatography on silica gel (pentane/
ethyl acetate, 4:1) to obtain after evaporation and drying in vacuo
the product as a white solid (58% yield).
Recrystallized N-bromosuccinimide (35 mg, 1 equiv) dissolved
in dichloromethane (1.5 mL) was added in 5 min dropwise to
a solution of 30,40,5,7-tetra-O-benzyl-4
b-(2-hydroxyethyloxy)-cat-
echin (140 mg, 197
m
mol) in dichloromethane (2 mL) at ꢀ78 ꢁC. The
reaction mixture was heated to room temperature and stirring was
continued at room temperature for 8 h. The mixture was extracted
with dichloromethane (10 mL). The organic layer was washed with
brine (3ꢂ10 mL) and then dried with MgSO4. The solvent was
evaporated under reduced pressure and after drying in vacuo, the
NMR: 1H (400 MHz, CDCl3, ppm): Two diastereomers Maj(
a
):-
min(
b
) 56:44.
d
¼7.02e6.84 (H20, H5, H60
a and b, m, 3H); 6.74
(H6D
(H3D
(H5D
b
b
b
, d, 1H, J6D,5D¼8.5 Hz); 6.68 (H6D
a
, d, 1H, J6D,5D¼8.5 Hz); 6.53
, d, 1H, J3D,5D¼2.3 Hz); 6.44
title product 6 was obtained as a beige solid (155 mg, 114 mmol,
, d, 1H, J3D,5D¼2.3 Hz); 6.48 (H3D
a
100% yield).
, dd, 1H, J5D,6D¼8.5 Hz, J5D,3D¼2.3 Hz); 6.34 (H5D
a
, dd, 1H,
Mp: 149e151 ꢁC.
J5D,6D¼8.5 Hz, J5D,3D¼2.3 Hz); 6.23 (H6
a
, d, 1H, J6,8¼2.1 Hz); 6.20
, d, 1H, J6,8¼2.1 Hz); 4.97
, d, 1H, J2,3¼8.7 Hz); 4.52
NMR: 1H (300 MHz, CDCl3, ppm)
d
¼0 7.32e7.51 (AreH, m, 20H);
7.19 (H20, d, 1H, J2 ,6 ¼1.9 Hz); 7.08 (H6 , dd, 1H, J6 ,5 ¼8.4 Hz); 7.02
(H50, d, 1H); 6.29 (H6, s, 1H); 5.18 (CH2Bn, s, 4H); 5.00 (CH2Bn, d,
4H); 5.11 (H2, d, 1H, J2,3¼10.9 Hz); 4.85 (H4, d, 1H, J4,3¼3.5 Hz);
3.92e3.68 (H3, H9 et H10, m 5H).
0
0
0
0
(H6
(H4
(H4
b
b
a
, d, 1H, J6,8¼2.1 Hz); 6.08 (H6
a
a
and
and
b
b
, d, 1H, J4,3¼5.5 Hz); 4.67 (H2
, d,1H, J4,3¼8.5 Hz); 4.33 (H3 , dd,1H, J3,2¼8.7 Hz, J3,4¼5.5 Hz);
b
4.04 (H3
3H); 3.87 (OCH3
a
, t, 1H, J3,2¼8.6 Hz); 3.89 (OCH3b, s, 3H); 3.88 (OCH3a, s,
a
and , s, 3H); 3.85 (OCH3 and , s, 3H); 3.80
b
a
b
13C (100.6 MHz, CDCl3, ppm)
d
¼157.2 (C5); 156.9 (C7); 152.4 (C8a);
(OCH3b, s, 3H); 3.79 (OCH3b, s, 3H); 3.77 (2 OCH3a, s, 6H); 3.60
(OCH3b, s, 3H); 3.43 (OCH3a, s, 3H).
149.3 (C40); 149.0 (C30); 137.3 (40-CqBn); 137.2 (30-CqBn); 137.5 (7-
CqBn); 136.1 (5-CqBn); 130.9 (C10); 128.8 (2 CHBn); 128.7 (2 CHBn);
128.5 (2 CHBn); 128.5 (2CHBn); 128.4 (2 CHBn); 128.1 (CHBn); 127.8
(CHBn); 127.6 (2 CHBn); 127.6 (2CHBn); 127.3 (2 CHBn); 127.0 (2
CHBn); 121.1 (C60); 114.7 (C50);114.3 (C20); 105.6 (C4a); 92.8 (C8); 92.2
(C6); 77.1 (C2); 73.3 (C9); 71.7 (C3); 71.4 (CH2Bn); 71.3 (CH2Bn); 71.2
(CH2Bn); 70.9 (CH2Bn); 70.0 (C4); 62.4 (C10).
13C (100.6 MHz, CDCl3, ppm)
d
¼160.6 (CqD
) 159.1 (C7 ); 158.6 (C7
); 156.3 (C8a
); 120.8 (C60
); 110.3 (C1D ); 105.2 (C4a
98.8 (C8 and C6); 93.9 (C6D , C5D and C3D ); 92.8 (C6D
b
); 160.1 (CqD
a
b
);
);
159.7 (CqD
158.0 (C5 ); 157.9 (C8a
131.3 (C10 ); 130.7 (C10
111.2 (C20); 110.8 (C1D
b
); 159.2 (CqD
a
a
b
b
b); 158.3 (C5
a
a
a
b
); 149.4e149.1 (C40 and C30);
b
); 120.5 (C60
); 105.0 (C4a
); 92.4
a
); 111.3 (C50);
a
a
b
);
a
a
a
b
SM [LSIMS, m/z (relative intensity %)]: 813 (100; [MþNa]þ); 790
(16), [MþH]þ; 729 (24); 721 (11); 571 (46); 549 (25); 457 (20); 329
(65); 307 (43); 289 (27).
(C5Db and C3Db); 82.5 (C2); 76.5 (C3); 56.1e55.5 (6 CH3); 35.2 (C4).
SMHR (m/z): [MꢀH]þ¼483.2026 (calculated for C27H31O8:
483.2013).
SMHR (m/z): [MþNa]þ¼811.1893 (calculated for C45H41BrO8Na:
811.1883).
4.3. 30,40,5,7-Tetra-O-benzyl-4
b-(2-hydroxyethyloxy)catechin
4.5. 30,40,5,7-Tetra-O-benzyl-4
b-(2-hydroxyethyloxy)-8-
Ethan-1,2-diol (104
dicyano-p-benzoquinone) (140 mg, 2 equiv) were added to a solu-
tion of 30,40,5,7-tetra-O-benzylcatechin (200 mg, 308
mol) in
m
L, 6 equiv) and DDQ (2,3-dichloro-5,6-
bromoepicatechin (11)
m
Recrystallized N-bromosuccinimide (226 mg, 1 equiv) dissolved
dichloromethane (4 mL) at room temperature. A green precipitate
appeared instantaneously. After 3 h of stirring at room temperature,
4-dimethylaminopyridine (37.6 mg, 2 equiv) was added. After an-
other 10 min of stirring, the solvent was evaporated. The resulting
crude material was purified by chromatography on silica gel (petro-
leum ether/ethyl acetate, 7:3) to obtain after evaporation and drying
in dichloromethane (10 mL) was added in 5 min dropwise to a so-
lution
of
30,40,5,7-tetra-O-benzyl-4
b-(2-hydroxyethyloxy)epi-
catechin (902 mg, 1.27 mmol) in dichloromethane (10 mL) at
ꢀ78 ꢁC. The reaction mixture was heated to room temperature and
stirring was continued at room temperature for 8 h. The mixture
was extracted with dichloromethane (100 mL). The organic layer
was washed with brine (3ꢂ100 mL) and then dried with MgSO4.
The solvent was evaporated under reduced pressure and after
drying in vacuo, the title product 11 was obtained as a beige solid
(1.010 g, 1.24 mmol, 98% yield).
in vacuo the product as a beige solid (151 mg, 213 mmol, 69% yield).
Mp: 120e122 ꢁC.
NMR: 1H (300 MHz, CDCl3, ppm)
d
¼07.34e7.51 (AreH, m, 20H);
7.09 (H20, d, 1H, J2 ,6 ¼1.5 Hz); 6 .98 (H6 , dd, 1H, J6 ,5 ¼8.5 Hz); 7.02
(H50, s, 1H); 6.27 (H6, d, 1H, J6,8¼1.9 Hz); 6.16 (H8, d, 1H); 5.17
(CH2Bn, s, 4H); 5.00 (CH2Bn, d, 4H); 5.06 (H2, d, 1H, J2,3¼12 Hz);
4.82 (H4, d,1H, J4,3¼3.5 Hz); 3.98e3.78 (H9 & H3, m, 3H); 3.66 (H10,
t, 2H).
0
0
0
0
Mp: 110e111 ꢁC.
NMR: 1H (300 MHz, CDCl3, ppm)
d
¼0 7.53e7.26 (AreH, m, 20H);
7.24 (H20, d, 1H, J2 ,6 ¼1.5 Hz); 7.05 (H6 , dd, 1H, J6 ,5 ¼8.3 Hz); 6.99
(H50, d, 1H); 6.29 (H6, s, 1H); 5.24e5.05 (CH2Bn, m, 8H); 5.03 (H2, d,
1H, J2,3¼6.08 Hz); 4.65 (H4, d, 1H, J4,3¼2.6 Hz); 4.05 (H3, m, 1H);
3.84e3.66 (H9 et H10, m, 4H).
0
0
0
0
13C (100.6 MHz, CDCl3, ppm)
d
¼160.9 (C7); 158.6 (C5); 156.0
(C8a); 149.4 (C40); 149.6 (C30); 137.3 (40-CqBn); 137.2 (30-CqBn);
136.6 (7-CqBn); 136.4 (5-CqBn); 131.3 (C10); 128.7 (4CHBn); 128.5
(4CHBn); 128.3 (CHBn); 128.1 (CHBn); 127.9 (2CHBn); 127.8
(2CHBn); 127.6 (4CHBn); 127.4 (2CHBn); 121.3 (C60); 115.0 (C50);
114.7 (C20); 104.6 (C4a); 94.9 (C8); 93.8 (C6); 73.3 (C9); 71.6
(CH2Bn); 71.3 (CH2Bn); 71.3 (C3); 71.1 (CH2Bn); 70.7 (C2); 70.6 (C4);
70.1 (CH2Bn); 62.4 (C10).
13C (100.6 MHz, CDCl3, ppm)
d
¼158.7 (C7); 157.0 (C5); 152.6
(C8a); 149.4 (C40); 149.0 (C30); 137.5 (40-CqBn); 137.4 (30-CqBn);
136.7 (7-CqBn); 136.4 (5-CqBn); 130.6 (C10); 129.0e127.3 (CHBn);
119.4 (C60); 115.5 (C50); 113.7 (C20); 103.8 (C4a); 93.1 (C8); 93.0 (C6);
75.5 (C2); 71.6e71.0 (CH2Bn); 70.6 (C9); 68.1 (C3); 62.2 (C10); 59.8
(C4).
SM [LSIMS, m/z (relative intensity %)]: 813 (100; [MþNa]þ); 790
(16, [MþH]þ); 729 (24); 721 (11); 571 (46); 549 (25); 457 (20); 329
(65); 307 (43); 289 (27).
SM [LSIMS, m/z (relative intensity %)]: 813 (100; [MþNa]þ); 790
(45), [MþH]þ; 727 (52); 637 (15); 547 (19); 479 (10); 457 (83); 413
(28); 381 (38); 361 (41); 329 (60); 289 (53).

S. Fabre et al. / Tetrahedron 71 (2015) 3045e3051
3049
SMHR (m/z): [MþNa]þ¼811.1878 (calculated for C45H41BrO8Na:
71.4 (C3); 71.3 (CH2Bn); 71.2 (CH2Bn); 70.9 (CH2Bn); 70.7 (CH2Bn);
68.7 (C4); 58.01 (OCH2CCH).
811.1883).
SM [LSIMS, m/z (relative intensity %)]: 807 (6); 805 (6); 437 (21);
316 (20); 289 (9); 288 (100); 228 (5); 227 (78); 214 (5); 213 (88);
173 (95); 143 (15); 141 (9).
4.6. 30,40,5,7-Tetra-O-benzyl-4
b-O-propargylcatechin
Propargyl alcohol (80
were added to
solution of 30,40,5,7-tetra-O-benzylcatechin
(100 mg, 154 mol) in dichloromethane (2 mL) at room tempera-
m
L, 9 equiv) and DDQ (70 mg, 2 equiv)
SMHR (m/z): [MþNa]þ¼805.1771 (calculated for C46H39O7NaBr:
805.1771).
a
m
ture. A green precipitate appeared instantaneously. After 3 h of
stirring at room temperature, 4-dimethylaminopyridine (37.6 mg,
2 equiv) was added. After another 10 min of stirring, the solvent
was evaporated. The resulting crude material was purified by
chromatography on silica gel (petroleum ether/ethyl acetate, 7:3) to
obtain after evaporation and drying in vacuo the product 3a as
4.8. 30,40,5,7-Tetra-O-benzyl-8-bromocatechin-4
a-(1, 3-
dimethoxybenzene) (7)
NaAuCl4$2H2O (0.05 equiv) was added to 30,40,5,7-tetra-O-ben-
zyl-4-hydroxy-8-bromocatechin (41 mg, 55 mol, 1 equiv) and 1,3-
dimethoxybenzene (15 l, 115 mol, 1 equiv) in dichloromethane
m
m
m
a beige solid (88 mg 123
m
mol, 81% yield).
(1 mL). The solution was stirred at room temperature for 12 h. The
organic layer was washed with brine and the aqueous phases were
extracted with dichloromethane. The organic phases were then
dried with MgSO4. After evaporation of the solvents, the crude
material was purified by chromatography on silica gel (petroleum
ether/ethyl acetate, 75:25) to obtain after evaporation and drying in
vacuo the product as a pink solid (80% yield).
Mp: 144e146 ꢁC.
NMR: 1H NMR (300 MHz, CDCl3, ppm) d0¼7.49e7.28 (AreH, m,
20H); 7.10 (H20, d, 1H, J2 ,6 ¼1.6 Hz); 7.03 (H6 , dd, 1H, J6 ,5 ¼8.6 Hz);
6.99 (H50, s, 1H); 6.27 (H6, d, 1H, J6,8¼2 Hz); 6.17 (H8, d, 1H); 5.18
(CH2Bn, s, 4H); 5.99 (CH2Bn, d, 4H); 5.06 (H2, d, 1H, J2,3¼6.2H); 4.95
(H4, d, 1H, J4,3¼3.1 Hz); 4.38 (OCH2CCH, dd, 2H, J¼3.4 Hz, J¼2.3 Hz);
3.93 (H3, ddd, 1H, J¼10.9 Hz, J3,2¼6.2 Hz, J3,4¼3.1 Hz); 2.36
(OCH2CCH, t, 1H, J¼2.3 Hz).
0
0
0
0
Mp: 55e57 ꢁC.
NMR: 1H (300 MHz, CDCl3, ppm):
d
¼7.50e7.21 (HeAr Bn, m,18H);
13C (100.6 MHz, CDCl3, ppm)
d
¼161.6 (C7); 158.2 (C5); 156.5
7.16 (H20 , s, 0.3H); 7.11 (H20
b a
, s, 0.7H); 6.69 (H60, d,1H, J6, 5 ¼5.0 Hz);
0
0
b
(C8a); 149.5 (C40); 149.2 (C30); 137.4 (40-CqBn); 137.4 (30-CqBn);
136.7 (7-CqBn); 136.3 (5-CqBn); 131.5 (C10); 128.8 (4 CHBn);
128.5 (4 CHBn); 128.3 (CHBn); 128.1 (CHBn); 127.9 (2 CHBn);
127.7 (2 CHBn); 127.6 (4 CHBn); 127.3 (2 CHBn); 121.4 (C60); 114.5
(C20); 115.0 (C50); 103.0 (C4a); 94.5 (C8); 93.6 (C6); 80.7
(OCH2CCH); 77.2 (C2); 74.5 (OCH2CCH); 71.6 (CH2Bn); 71.3
(CH2Bn); 70.6 (CH2Bn); 70.4 (CH2Bn); 70.3 (C3); 69.0 (C4); 58.3
(OCH2CCH) ppm.
6.88 (H50, d,1H); 6.79 (HeAr, d,1H); 6.53 (HeAr, 2s,1H); 6.37 (H6D, d,
1H, J6,5¼2.31 Hz); 6.28 (H5D, d, 1H, J5D,3D¼2.48); 6.26 (H3D, d, 1H);
6.24 (H6, s, 1H); 5.13 (CH2Bn, m, 6H); 4.80 (H2, d, 1H, J2,3¼8.35 Hz);
4.76 (CH2Bn-5A
J¼8.35 Hz); 4.15 (H3
3.78 (2-OCH3, 2s, 0.6H); 3.76 & 3.63 (2-OCH3, 2s, 1.4H).
13C (100.6 MHz, CDCl3, ppm):
a
, t, 0.7H, J¼8.35 Hz); 4.56 (CH2BN-5A
b
& H, d, 1.3H,
b
, m, 0.3H); 4.02 (H3
a, t, 0.7H, J2,3¼8.0 Hz); 3.82 &
d
¼159.3 (CqD); 158.0 (CqD); 156.8
(C7); 155.9 (C5); 155.3 (C8a); 149.1 (C40 & C30); 137.6 (CqBn); 137.5
(CqBn); 136.9 (CqBn); 136.5 (CqBn); 131.1 (C10); 128.8e127.0
(CHBn); 125.1 (C4a); 120.6 (C60); 115.0 (C50); 113.9 (C20); 108.8
(C1D); 105.2 (C5D); 98.8 (C6D); 93.8 (C3D); 93.3 (C8); 92.8 (C6);
SM [LSIMS, m/z (relative intensity %)]: 813 (100) [MþNa]þ; 790
(45) [MþH]þ; 27 (52); 637 (15); 547 (19); 479 (10); 457 (83); 413
(28); 381 (38); 361 (41); 329 (60); 289 (53).
SMHR (m/z): [MþNa]þ¼811.1878 (calculated for C45H41BrO8Na:
811.1883).
81.8 (C2); 76.3 (C3a); 71.5 (4 CH2Bn); 70.4 (C3b); 55.9 (CH3); 55.6
(CH3); 40.4 (C4).
SM [LSIMS, m/z (relative intensity %)]: 889 (100); 888 (31); 887
(77); 365 (44); 360 (26); 347 (42); 327 (40); 301 (72); 282 (36); 251
(35); 240 (52).
4.7. 30,40,5,7-Tetra-O-benzyl-4
b-O-propargyl-8-bromocatechin
(13)
SMHR (m/z): [MþNa]þ¼887.2190 (calculated for C51H45O8NaBr:
887.2190).
Recrystallized N-bromosuccinimide (20 mg, 1 equiv) dissolved
in dichloromethane (1.5 mL) was added in 5 min dropwise to
a
solution of 30,40,5,7-tetra-O-benzyl-4
b
-O-propargylcatechin
4.9. 30,40,5,7-Tetra-O-benzyl-8-bromocatechin-(4
tetra-O-benzylcatechin (9)
a
8)-30,40,5,7-
(80 mg, 114
m
mol) in dichloromethane (3 mL) at ꢀ78 ꢁC. The re-
action mixture was warmed to room temperature and stirring was
continued at room temperature for 8 h. The reaction mixture was
extracted with dichloromethane (10 mL). The organic layer was
washed with brine (3ꢂ10 mL) and then dried with MgSO4. The
solvent was evaporated under reduced pressure and after drying in
vacuo, the title product 13 was obtained as a beige solid (90 mg,
4.9.1. From 30,40,5,7-tetra-O-benzyl-4
bromocatechin (6). With AuCl (0.05 equiv) was added to 30,40,5,7-
tetra-O-benzyl-4 -O-propargyl-8-bromocatechin (88 mg,
mol, 1 equiv) and 30,40,5,7-tetra-O-benzylcatechin (73 mg,
mol, 1 equiv) in dichloromethane (2 mL). The solution was
b-(2-hydroxyethyloxy)-8-
b
6
112
112
m
m
114
m
mol, 100% yield).
stirred at room temperature for 4 h. The organic layer was washed
with brine and the aqueous phases were extracted with dichloro-
methane. The organic phases were then dried with MgSO4. After
evaporation of the solvents, the crude material was purified by
chromatography on silica gel (petroleum ether/ethyl acetate, 7:3) to
obtain after evaporation and drying in vacuo the product 9 as a pink
solid (67% yield).
Mp: 147e149 ꢁC.
NMR: 1H (300 MHz, CDCl3, ppm)
d
¼7.40e7.20 (AreH, m, 20H);
7.09 (H20, d, 1H, J2 ,6 ¼1.9); 6.97 (H6 , dd, 1H, J6 ,5 ¼8.2 Hz); 6.97 (H5 ,
d,1H); 6.17 (H6, s,1H); 5.18 (CH2Bn, s, 4H); 5.99 (CH2Bn, d, 4H); 4.99
(H2, d, 1H, J2,3¼8.8 Hz); 4.87 (H4, d, 1H, J4,3¼3.6 Hz); 4.27
(OCH2CCH, dd, 2H, J¼3.3 Hz, J¼2.5 Hz); 3.70 (H3, m, 1H); 2.39
(OCH2CCH, s, 1H).
0
0
0
0
0
0
NaAuCl4$2H2O (0.05 equiv) was added to 30,40,5,7-tetra-O-
13C (100.6 MHz, CDCl3, ppm)
d
¼157.3 (C5); 157.2 (C7); 152.8
benzyl-4
b
-O-propargyl-8-bromocatechin
6
(61 mg,
8
m
m
mol,
mol,
(C8a); 149.3 (C40); 149.2 (C30); 137.5 (40-CqBn); 137.3 (30-CqBn);
136.5 (7-CqBn); 136.0 (5-CqBn); 131.3 (C10); 128.8 (2 CHBn); 128.7
(2 CHBn); 128.6 (2 CHBn); 128.5 (2 CHBn); 128.5 (CHBn); 128.1
(CHBn); 127.8 (2 CHBn); 127.8 (2 CHBn); 127.6 (2 CHBn); 127.3 (4
CHBn); 127.0 (2 CHBn); 121.1 (C60); 114.7 (C50); 114.3 (C20); 104.4
(C4a); 92.8 (C8); 91.9 (C6); 77.1 (C2); 74.6 (OCH2CCH); 71.9 (CH2Bn);
1 equiv) and 30,40,5,7-tetra-O-benzylcatechin (50 mg, 8
1 equiv) in dichloromethane (1.5 mL). The solution was stirred at
room temperature for 4 h. The organic layer was washed with
brine and the aqueous phases were extracted with dichloro-
methane. The organic phases were then dried with MgSO4. After
evaporation of the solvents, the crude material was purified by

3050
S. Fabre et al. / Tetrahedron 71 (2015) 3045e3051
chromatography on silica gel (petroleum ether/ethyl acetate, 4:1)
to obtain after evaporation and drying in vacuo the product 9 as
a pink solid (80% yield).
Maj); 73.8 (C3C, min); 73.6 (C3C, Maj); 71.9e70.5 (CH2Bn, min &
Maj); 69.3 (C3F, min); 69.0 (C3F, Maj); 38.0 (C4C, min); 37.9 (C4C,
Maj); 29.1 (C4F, min); 28.6 (C4F, Maj).
FeCl3 (0.05 equiv) was added to 30,40,5,7-tetra-O-benzyl-4
b
-O-
mol, 1 equiv) and
mol, 1 equiv) in
SM [LSIMS, m/z (relative intensity %)]: 1401 (87; [MþNa]þ); 1378
(58; [MþH]þ); 1309 (16); 1045 (25); 937 (26); 727 (35); 647 (21);
395 (64); 307 (42); 211 (100).
propargyl-8-bromocatechin 6 (38 mg, 4.8
m
30,40,5,7-tetra-O-benzylcatechin (31 mg, 4.8
m
dichloromethane (1 mL). The solution was stirred at room tem-
perature for 4 h. The organic layer was washed with brine and the
aqueous phases were extracted with dichloromethane. The or-
ganic phases were then dried with MgSO4. After evaporation of
the solvents, the crude material was purified by chromatography
on silica gel (petroleum ether/ethyl acetate, 4:1) to obtain after
evaporation and drying in vacuo the product 9 as a pink solid (62%
yield).
SMHR
(m/z):
[MþNa]þ¼1399.4160
(calculated
for
C
86H73BrO12Na: 1399.4183).
4.10. 30,40,5,7-Tetra-O-benzyl-8-bromoepicatechin-(4
30,40,5,7-tetra-O-benzylcatechin (12)
b8)-
Mp: 63e66 ꢁC.
NMR: 1H (CDCl3, 300 MHz, ppm): Two rotamers (Maj/min,
77:23):
d
¼7.50e7.26 (AreH, m); 7.21e6.80 (H20B & H20E, H50B,
4.9.2. From 30,40,5,7-tetra-O-benzyl-4
bromocatechin (11). NaAuCl4$2H2O (0.05 equiv) was added to
30,40,5,7-tetra-O-benzyl-4
-O-propargyl-8-bromocatechin 11
(61 mg, 8
mol, 1 equiv) and 30,40,5,7-tetra-O-benzylcatechin
(50 mg, 8 mol, 1 equiv) in dichloromethane (1.5 mL). The solution
b-O-propargyl-8-
H60B/E, H50E min & Maj); 6.64 (H2B/E, Maj, J2 ,6 Maj¼1.5 Hz); 6.35
0
0
(H6D, Maj, s); 6.32 (H60E/B, Maj, dd, J6 ,5 ¼8.3 Hz, J6 ,2 ¼1.9 Hz); 6.20
(H6A, min, s); 6.17 (H6D, min, s); 6.05 (H6A, Maj, s); 5.45 (H2C, Maj,
s); 5.38 (H2C, min, s); 4.80 (H4C, Maj, d, J4,3CMaj¼1.1 Hz); 4.73 (H4C,
min, d, J4,3Cmin¼1.0 Hz); 4.62 (H2F, min, d, J2,3Fmin¼8.5 Hz); 4.07
(H3C, d, J3,4CMaj¼1.1 Hz); 3.93 (H3C, min, m); 3.69 (H3F, Maj, m);
0
0
0
0
b
m
m
was stirred at room temperature for 4 h. The organic layer was
washed with brine and the aqueous phases were extracted with
dichloromethane. The organic phases were then dried with MgSO4.
After evaporation of the solvents, the crude material was purified
by chromatography on silica gel (petroleum ether/ethyl acetate,
4:1) to obtain after evaporation and drying in vacuo the product 9
as a pale pink solid (58% yield).
3.58 (H2F, Maj, d, J2,3FMaj¼11.3 Hz); 3.23 & 2.55 (H4F
a
& H4Fb, Maj,
ABX, J4F ¼6.4 Hz,J4F
¼16.7 Hz, J4F
¼9.8 Hz); 3.14 &
a
,4F
b
Maj
a
,3FMaj
b,3FMaj
¼16.2 Hz J4F
2.68 (H4F
a
& H4F
b
, min, ABX, J4F
¼5.3 Hz,
a
,4Fb
min
a,3Fmin
J4F
¼9.0 Hz).
b
,3Fmin
13C (100,6 MHz, CDCl3, ppm): Two rotamers (Maj/min 77/23):
d
¼156.0 (C5D); 155.8 (C7D); 155.6 (C5A); 154.3 (C7A & C8aD); 151.4
FeCl3 (0.05 equiv) was added to 30,40,5,7-tetra-O-benzyl-4
b
-O-
mol, 1 equiv) and
mol, 1 equiv) in
(C8aA); 149.8, 149.4, 149.2 & 148.6 (C30B, C30E, C40B, C40E);
137.6e136.9 (CqBn); 131.8 & 129.5 (C10B, C10E); 128.6e126.8
(CHBn); 120.3 & 119.1 (C60B, C60E); 115.2 & 114.3 (C50B, C50E); 113.1
& 11.3 (C20B & C20E); 110.8 (C8D); 106.8 (C4aA); 104.3 (C4aD); 93.4
(C8A); 92.5 (C6D); 92.4 (C6A); 81.6 (C2F, Maj); 81.4 (C2F, min); 77.2
(C2C, min); 75.9 (C2C, Maj); 72.1e69.5 (CH2Bn, min & Maj); 73.8
(C3C, min); 73.6 (C3C, Maj); 71.9e70.5 (CH2Bn, C3C min & Maj);
68.5 (C3F, Maj); 68.2 (C3F, min); 35.8 (C4C, Maj & min); 29.7 (C4F,
Maj); 28.9 (C4F, min).
propargyl-8-bromocatechin 11 (35 mg, 4.5
m
30,40,5,7-tetra-O-benzylcatechin (29 mg, 4.5
m
dichloromethane (1 mL). The solution was stirred at room tem-
perature for 4 h. The organic layer was washed with brine and the
aqueous phases were extracted with dichloromethane. The or-
ganic phases were then dried with MgSO4. After evaporation of
the solvents, the crude material was purified by chromatography
on silica gel (petroleum ether/ethyl acetate, 4:1) to obtain after
evaporation and drying in vacuo the product 9 as a pale pink solid
(74% yield).
SM [LSIMS, m/z (relative intensity %)]: 1417 (14; [MþK]þ); 1401
(100; [MþNa]þ); 712 (5).
Mp: 73e76 ꢁC.
SMHR
(m/z):
[MþNa]þ¼1399.4234
(calculated
for
NMR: 1H (CDCl3, 300 MHz, ppm): Two rotamers (Maj/min,
C86H73BrO12Na: 1399.4183).
63:37):
d
¼7.56e7.24 (AreH, m); 7.19e7.04 (H20B & H20E, min &
Maj); 6.99e6.83 (H50B, min & Maj, H50E Maj); 6.93e6.83 (H60B, min
& Maj); 6.78 (H50E, min, d, J5 ,6 Emin¼1.5 Hz); 6.32 (H6D, Maj, s); 6.29
4.11. One step debromination/debenzylation of protected
procyanidin dimers (9) and (12)
0
0
(H60E, min, d, J6 ,5 Emin¼1.5 Hz); 6.26 (H6A, min & H60E, Maj); 6.24
(H6A, Maj, s); 6.15 (H6D, min, s); 5.34e4.49 (CH2Bn, min & Maj, m);
4.88 (H4C, min, d, J4,3Cmin¼8.3 Hz); 4.80 (H4C, Maj, d,
J4,3CMaj¼9.03 Hz); 4.62 (H2C, min & Maj, d, J2,3C¼9.8 Hz); 4.44 (H2F,
min, d, J2,3Fmin¼8.7 Hz); 4.32 (H3C, Maj, m); 4.19 (H3C, min, m); 3.73
(H3F, min & Maj, m); 3.72 (H2F, Maj, d, J2,3FMaj¼12.1 Hz); 3.26 & 2.70
0
0
To
8)-30,40,5,7-tetra-O-benzylcatechin (9) (40 mg, 29
solved in ethyl acetate (2 mL) and methanol (2 mL) was added
Pearlman’s catalyst (Pd(OH)2/C 20% and triethylamine (20 L)). The
a
solution of 30,40,5,7-tetra-O-benzyl-8-bromocatechin-
mol) dis-
(4a
m
m
(H4F
a
& H4F
b
, min, ABX, J4F
¼16.6 Hz J4F
¼5.8 Hz,
solution was stirred at room temperature for 19 h under H2 at-
mosphere. After filtration of the reaction mixture over Celite and
washing up with ethyl acetate, the solvents were evaporated under
reduced pressure. After rapid filtration of the crude over silica
(acetone/methanol, 96:4), procyanidin B3 (10) was obtained as
a pale pink solid (100% yield).
a
,4F
b
min
a,3Fmin
J4F
¼9.4 Hz); 3.11
&
2.46 (H4F
a
&
H4Fb, Maj, ABX,
b
,3Fmin
J4F
¼16.2 Hz, J4F
¼4.9 Hz,J4F
,3FMaj
¼8.5 Hz).
,3FMaj
a
,4F
b
Maj
a
b
13C (100.6 MHz, CDCl3, ppm, two rotamers, Maj/min 63/37):
d¼157.6 (C7A, min); 156.9 (C7A, Maj); 156.8 (C7D, min); 156.2 (C7D,
Maj); 156.2 (C5D, min); 156.1 (C5D, Maj); 154.7 (C5A, Maj); 154.7
(C5A, min); 154.5 (C8aA, Maj); 154.2 (C8aA, min); 154.0 (C8aD,
Maj); 153.4 (C8aD, min); 149.8e148.6 (C30B, C30E, C40B, C40E, min &
Maj); 137.2e137.0 (CqBn, min & Maj); 132.3 (C10E, Maj); 132.2 (C10B,
min); 132.1 (C10B, Maj); 130.6 (C10E, min); 130.2e127.5 (CHBn, min
& Maj); 121.6 (C60B, Maj); 121.1 (C60B, min); 120.7 (C60E, Maj); 120.3
(C60E, min); 116.1 (C50B, min); 115.4 & 115.2 (C50B & C50E, Maj); 115.1
(C50E, min); 114.5 (C20B & C20E, min); 114.1 (C20B & C20E, Maj); 112.2
(C8D, min); 111.9 (C8D, Maj); 111.2 (C4aA, Maj); 111.1 (C4aA, min);
104.0 (C4aD, min); 103.0 (C4aD, Maj); 94.4 (C8A, min); 94.3 (C8A,
Maj); 94.1 (C6A, Maj); 93.8 (C6A, min); 92.3 (C6D, min); 91.8 (C6D,
Maj); 82.7 (C2C, Maj); 82.3 (C2C, min); 81.9 (C2F, min); 81.3 (C2F,
Mp: 218e220 ꢁC (dec) for procyanidin B3 (10).
SM [LSIMS, m/z (relative intensity %)]: 579 (15; [MþH]þ); 473
(13); 449 (22); 433 (14); 413; (21); 329 (30); 306 (23); 289 (27); 284
(100); 247 (27).
SMHR (m/z): [MþNa]þ¼601.1319 (calculated for C30H26O12Na:
601.1322).
Mp: 204e205 ꢁC (dec) for procyanidin B1.
SM [LSIMS, m/z (relative intensity %)]: 601 (20; [MþNa]þ); 409
(4); 381 (12); 353 (15); 329 (48); 311 (5); 242 (100); 212 (14).
SMHR (m/z): [MþNa]þ¼601.1318 (calculated for C30H26O12Na:
601.1322).

S. Fabre et al. / Tetrahedron 71 (2015) 3045e3051
3051
All NMR 1H and 13C data of procyanidins B3 (10) and B1 were
found identical to those fully described and published previously by
our group.17
€
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€
€
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Acknowledgements
This work was financially supported by the CIVB (In-
terprofessional Council of Bordeaux Wines) through a grant to S.F.
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