An improved and versatile method for the rapid synthesis of aryldihydrobenzofuran systems by a boron tribromide-mediated cyclization reaction

Article abstract of DOI:10.1002/hlca.200390036

Boron tribromide is presented as a highly reactive reagent that simultaneously allows the demethylation and fully diastereoselective cyclization of different precursor molecules, obtained by an aldol-type reaction, to a series of hydroxylated aryldihydrobenzofuran systems in racemic form. The latter are often found as key structures in natural compounds of different classes. Syntheses of educts, which mainly took advantage of a versatile Rieche formylation, are also described.

Full text of DOI:10.1002/hlca.200390036

Helvetica Chimica Acta Vol. 86 (2003)
343
An Improved and Versatile Method for the Rapid Synthesis of
Aryldihydrobenzofuran Systems by a Boron Tribromide-Mediated Cyclization
Reaction
by Richard Detterbeck1) and Manfred Hesse*
Organisch-chemisches Institut der Universit‰t Z¸rich, Winterthurerstrasse 190, CH-8057 Z¸rich
(tel.: ‡41-1-6354281; fax: ‡41-1-6356812; e-mail: mtbohley@oci.unizh.ch)
Boron tribromide is presented as a highly reactive reagent that simultaneously allows the demethylation
and fully diastereoselective cyclization of different precursor molecules, obtained by an aldol-type reaction, to a
series of hydroxylated aryldihydrobenzofuran systems in racemic form. The latter are often found as key
structures in natural compounds of different classes. Syntheses of educts, which mainly took advantage of a
versatile Rieche formylation, are also described.
1. Introduction. Viewing a whole list of polyamine alkaloids [1], the spermine
alkaloid aphelandrine2) and the related class of ephedradines (see 1 4) attract
attention in view of their structural complexity. Undoubtedly, this arises from the
incorporation of two hydroxylated aromatic systems, which are linked together to form
an aryldihydrobenzofuran system. Such a system is not only an integral part of the
mentioned polyamine alkaloids but also of compounds that belong to other groups of
natural products, for example the flavonoids [2], lignans [3][4], and depsides [5]. The
latter group contains, in particular, the salvianolic acids, which will be discussed below.
In contrast to the biological relevance of the aryldihydrobenzofuran moiety, only quite
a few synthetic procedures for such compounds can be found in the literature. Most of
the published work dealing with the preparation of aryldihydrobenzofuran systems
involved a synthetic procedure is referred to as phenolic oxidation [6]. The importance
of such a reaction for the biosynthesis of aphelandrine has been shown impressively by
¬
Nezbedova et al. [7]. In sharp contrast to its unquestioned relevance for in vivo
synthesis, in the laboratory, this reaction proved to suffer from serious disadvantages,
e.g., the yields are usually low and the range of obtainable substitution patterns at the
two aromatic rings is rather limited. So it became obvious to us that, in the course of our
synthetic projects, we should look for an alternative procedure, which should not only
allow the preparation of different hydroxylated aryldihydrobenzofurans but which also
must be operationally simple and, in addition, require only inexpensive starting
materials. A corresponding literature search revealed a strategy to construct the
aryldihydrobenzofuran framework first published by Nakatsubo and Higuchi [8]; the
same method was again mentioned almost one decade later by Baker et al. [9]. Therein,
1
)
)
Part of the Ph.D. thesis of R. D., University of Z¸rich, 2002.
Aphelandrine and orantine (ˆephedradine A; 1) are epimers with respect to the two stereogenic centers
at the dihydrobenzofuran ring.
2

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Helvetica Chimica Acta Vol. 86 (2003)
the key steps are an aldol-type reaction between an aromatic aldehyde and a
phenylacetic ester derivative, followed by a ring closure mediated by the Lewis acid
BF3 ¥ Et2O. Verifying these synthetic steps, we found them to satisfy our claims in
principal. On the other hand, the procedures provided by these authors for preparing
the necessary phenylacetic ester derivatives are rather tedious and, therefore, not at all
satisfying. To make a long story short: literature offered us a valuable synthetic strategy,
but we had to work out the scope and limitations of this process for ourselves and also
to find a convenient access to the starting materials.
2. Results and Discussion. The first synthetic targets we chose were the closely
related aryldihydrobenzofuran systems 5 and 6 deduced from the macrocyclic spermine
alkaloids orantine (ˆephedradine A; 1) and ephedradine B (2) and C (3). retro-
Synthetic analysis according to the strategy of [8] as shown in Scheme 1 revealed the
building blocks 7 and 8 or 9 for a synthesis of 5 and 6.
Scheme 1
OH
OH
OCH3
H3CO
H3CO
O
H
O
H
O
H
O
H
O
H
O
N
N
N
H
O
O
O
NH
NH
NH
H
H
H
HN
NH
HN
NH
HN
NH
2 ephedradine B
1 orantine (= ephedradine A)
3 ephedradine C
R
OH
O
5 R = H
6 R = OH
COOCH3
HOOC
OCH3
R
OCH3
COOCH3
+
O
H
C
8 R = H
9 R = CH3O
O
H
7

Helvetica Chimica Acta Vol. 86 (2003)
345
Obviously, the availability of 8 and 9 represent no problem because 8 is
anisaldehyde, and 9 is veratrumaldehyde, which are both inexpensive commercial
compounds. So we focused on the synthesis of phenylacetic ester derivative 7. Very
surprisingly, for the formation of such a simple compound, the literature offers only the
elaborate procedure of Baker et al. mentioned above. Recognizing the availability of
(2-methoxyphenyl)acetic acid (10), we were able to prepare 7 easily in multigram
amounts by a very smooth two-step reaction sequence (Scheme 2): an esterification
with MeOH to 11 was accomplished by a comparatively unknown formylation method,
the so-called Rieche formylation [10] involving as a formylating agent dichloromethyl
methyl ether in combination with stoichiometric amounts of SnCl4. Fortunately, this
procedure not only allowed the isolation of almost quantitative yields of the desired 7
after a rapid reaction but also provided the product with complete regioselectivity, i.e.,
apart from the normal extraction procedure, purification was unnecessary. The
projected aldol-type reaction with the aldehydes 8 or 9 first required suitable
protection of the formyl group of 7, which was perfectly achieved by its transformation
to the standard dimethyl acetal derivative 12 with trimethyl orthoformate. Acetal
derivative 12 was stable enough to facilitate the following aldol-type reaction. On the
other hand, the acetal moiety was easily hydrolyzed during the subsequent workup
procedure, therefore uncovering the formyl moiety for the final Knoevenagel
condensation. For the aldol-type reaction (an equilibrium reaction) of 12 with 8 or 9,
Scheme 2
OCH3
OCH3
OCH3
OH
OCH3
OCH3
a)
c)
O
O
O
H
OCH3
R
H3CO
11 R = H
7 R = CHO
b)
10
12
d)
8 or 9
R
O
OH
OH
R
H3CO
H3CO
O
e)
f)
5
OCH3
O
COOCH3
H
H
O
15 R = H
16 R = OH
13 R = H
14 R = CH3O
a) SOCl2, MeOH, 08, 1 h; 98%. b) Cl2CHOMe, SnCl4, CH2Cl2, 08 ! r.t., 2 h; 98%. c) HC(OMe)3, MeOH,
NH4Cl, reflux, 2 h; 88%. d) 1. LDA, Et2O, À788, 30 min; 77%; 2. aq. HCl soln., 1 min, r.t.; quant. e) BBr3,
CH2Cl2, 08, 2 h; 68%. f) CH2(COOH)2, piperidine, pyridine, reflux, 2 h; 97%.

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Helvetica Chimica Acta Vol. 86 (2003)
it proved to be of greatest importance to carry out the whole reaction, including the
quenching process, at low temperature (À 788) because only then does the equilibrium
favor the products. Deprotonation of 12 was best done by lithium diisopropylamide
(LDA) in Et2O, followed by addition of the appropriate aldehyde. As equilibrium was
always attained rapidly, prolonged reaction times did not increase the yield. Workup
under mildly acidic conditions liberated the aldol products 13 and 14, respectively, each
as an inseparable mixture of two diastereoisomers. Fortunately, this outcome was of no
importance because the subsequent cyclization of 13 and 14 transformed both
diastereoisomers of each aldol product into the desired aryldihydrobenzofuran systems
15 and 16, respectively. We were very pleased to see that an excess of boron tribromide
not only liberated from the MeO groups of 13 or 14 the phenolic OH groups needed for
the cyclization step but also promoted the latter in situ to give the aryldihydrobenzo-
furan systems 15 or 16, respectively, in good to excellent yields. It may be justified to
emphasize the role of boron tribromide as a deprotecting and cyclization reagent,
making, thus, the whole transformation highly user-friendly, especially when taking into
account the simple reaction conditions, which do not even require any specially dried
solvent or protecting atmosphere. The NMR spectra of the racemic products 15 and 16
clearly established the presence of just one diastereoisomer in each case, i.e., the
(hydroxylated) aryl moiety and the COOMe group both connected to the dihydrofuran
moiety were in either cis- or trans-relationship, but definitely, no mixture was present.
Since it is known that coupling constants although easily observeable are of no
significance in such five-membered rings, we could not determine the cis- or trans-
configuration from the NMR data. This difficulty, indeed, once led to a wrong
presumption by Stoessl [11] about the relative configuration of hordatine A (an
antifungal factor of barley) in which the aryldihydrobenzofuran system 5 is
incorporated. Confronted with an analogous question, Yoshihara et al. [4] decided to
solve the configuration problem by comparison and correlation of the chemical shifts of
configurationally known derivatives. Therefore, they were able to establish the trans-
configuration in their case. Even so, one may expect increased thermodynamic stability
for the trans-configuration, we actually had no final proof in hand that the arguments of
Yoshihara were also true in our case. Luckily, it was possible to crystallize 16, so the
assumed trans-configuration could be secured unequivocally by an X-ray single-crystal
analysis (see Fig. 1).
Exemplarily for 15, we continued with the construction of such an a,b-unsaturated
carboxylic acid side-chain via Knoevenagel condensation as one is present, e.g., in
the above-mentioned polyamine alkaloid hordatine A. By a standard procedure, 5 was
obtained without any problems (Scheme 2), suggesting that 6 might be formed
analogously. Following the general synthetic pathway, but varying the aldehyde used in
the aldol-type reaction, there are surely a great range of different substitution patterns
feasible.
Encouraged by these results, we went on to the retro-synthetic analysis of
ephedradine D (4) with the focus on the aryldihydrobenzofuran system 17 integrated
there. As shown in Scheme 3, the above-exemplified synthetic strategy required as
starting materials phenylacetic acid derivative 18 and anisaldehyde (8).
This time, a literature search was completely unsuccessful. For obvious reasons of
chemical similarity and inexpensiveness, we chose vanillin (19) as our starting material

Helvetica Chimica Acta Vol. 86 (2003)
347
Fig. 1. ORTEP Plot [12] of the aryldihydrobenzofuran skeleton 16
Scheme 3
OH
OH
OH
O
O
O
H
O
COOCH3
H
N
17
H
H3CO
O
NH
OCH3
H
H3CO
COOCH3
HN
NH
+ 8
4 ephedradine D
C
H
18
O
for the synthesis of 18 (Scheme 4). First, 19 was allylated at the free OH group ( ! 20)
by allyl bromide, and then an allyl migration yielding 21 was achieved according to a
Claisen mechanism by means of heating 20 in mesitylene as an inert and high-boiling
solvent. After methylation of the now free OH group by MeI ( ! 22) and subsequent
acetalization, compound 23 was obtained in high overall yield. Unfortunately, the
projected split-off of the CˆC bond proved to be more problematic, so neither
ozonolysis nor the attempted oxidation by means of RuO4/NaIO4 was successful.
Finally, a LemieuxÀvan Rudloff oxidation (substoichiometric amounts of KMnO4
together with an excess of NaIO4) allowed the isolation of acid 24 in moderate yield. As

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Helvetica Chimica Acta Vol. 86 (2003)
Scheme 4
O
OR
OH
OCH3
H3CO
H3CO
H3CO
H3CO
a)
b)
d)
H
OCH3
O
H
O
H
O
H
H3CO
19
21 R = H
22 R = CH3
23
20
c)
e)
OCH3
OCH3
OCH3
H3CO
OCH3
H3CO
OCH3
O
H3CO
OH
g)
f)
O
O
H
OCH3
H3CO
O
H
O
H
25
18
24
h)
O
OH
OH
OH
H3CO
H3CO
O
j)
i)
17
OCH3
H
COOCH3
OCH3
H3CO
HOOC
OCH3
26
27
a) CH2ˆCHCH2Br, K2CO3, acetone, reflux, 8h; 90%. b) Mesitylene, reflux, 24 h; 88%. c) MeI, K2CO3, DMF,
t
r.t., 8h; 92%. d) HC(OMe)3, MeOH, NH4Cl, reflux, 2 h; 95%. e) KMnO4, NaIO4, K2CO3, BuOH/H2O, r.t.,
4 h; 51%. f) SOCl2, MeOH, 08, 1.5 h; 75%. g) HC(OMe)3, MeOH, NH4Cl, reflux, 2 h; 75%. h) LDA, 8, Et2O,
À788, 1 h; 73%. i) BBr3, CH2Cl2, 08, 1.5 h; 82%. j) CH2(COOH)2, piperidine, pyridine, reflux, 2 h; 92%.
the workup procedure required acidic conditions, the dimethyl acetal inevitably was
also hydrolyzed. After two steps of routine synthesis, esterification ( ! 18) and
acetalization, the precursor 25 for the aldol-type reaction was obtained. The latter
could be performed with anisaldehyde (8) as described above. Again, the aldol product
26 was formed as a mixture of diastereoisomers. All mentioned reactions before the
aldol-type reaction could be optimized in such a manner that only the usual extractive
workup but no chromatographic separation was necessary; despite the somewhat
prolonged reaction sequence, rapid success was ensured. Also successful was the

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349
application of boron tribromide as deprotecting/coupling reagent to furnish the desired
aryldihydrobenzofuran 17 in one additional step, and, finally, the a,b-unsaturated acid
side-chain was constructed by a Knoevenagel condensation yielding 27. Attention may
be drawn to the difference in reactivity of the two carboxylic acid functionalities of 27,
one being present as an ester and the other as the free acid, so regioselectivity for
further synthetic operations is ensured effortlessly.
Concomitant to our work on the aryldihydrobenzofuran systems present in
polyamine alkaloids, we were in search of a further substance class to test the
usefulness of our new method. For this purpose, some natural products of the plant
Salvia miltiorrhiza Bunge (Labiatae) the so-called salvianolic acids [5][13][14]
proved to be of high interest. Such compounds are well known in Chinese medicine for
the treatment of coronary diseases [15]. At least in salvianolic acid B (28) [5] and the
related compounds lithospermic acid (29) isolated from Lithospermum ruderale
Dougl. ex Lehm. (Boraginaceae) [16]
as well as in przewalskinic acid (30)
isolated from Salvia przewalskii Maxim. (Labiatae) [17] there is also a aryldihy-
drobenzofuran skeleton present, which differs in substitution pattern from the already
mentioned ones. A comparison of both aryldihydrobenzofuran skeletons is shown in
Fig. 2.
Type 1; present, e.g., in
polyamine alkaloids
Type 2; present, e.g., in
salvianolic acids
OH
OH
OH
OH
OH
O
OH
O
COOR2
COOR'
COOH
C
H
H
ROOC
H
COOR1
CH2
28 R1 = R2 = X
29 R1 = X, R2 = H
30 R1 = R2 = H
X =
OH
OH
derived from (2R)-3-(3,4-dihydroxyphenyl)lactic acid
Fig. 2. Comparison of the substitution patterns of different aryldihydrobenzofuran skeletons present in natural
products
Moreover, below we would like to exemplify that our synthetic strategy, initially
focussed on the preparation of przewalscinic acid (30), allowed en passant the synthesis
of the principal skeletons 31 and 32 of two more natural products salvianolic acid D
(33) and salvianolic acid E (34) (see below, Schemes 5 and 6). Following the retro-
synthetic analysis, it was obvious that we needed access to the aromatic aldehyde 35 and
its dimethyl acetal 36. For the synthesis of 35 (Scheme 5) on a multigram scale, we once

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Helvetica Chimica Acta Vol. 86 (2003)
Scheme 5
H3CO
O
H3CO
H3CO
H3CO
H3CO
CH2R
H3CO
CH2COOR
a)
d)
H
39 R = OH
42 R = H
37 R = CH3
b)
c)
e)
38
40 R = Cl
41 R = CN
f)
H3CO
H3CO
H3CO
H3CO
g)
COOCH3
OCH3
COOCH3
H
+ 18
7.5%
75%
OCH3
O
35
36
h)
OR1
OCH3
OR1
COOH
OCH3
COOCH3
i)
COOR2
COOH
31 R1 = CH3, R2 = H
33 R1 = H, R2 = X
43
a) NaBH4, MeOH, r.t., 2 h; 99%. b) SOCl2, pyridine, CHCl3, r.t., 45 min; 95%. c) KCN, EtOH/H2O, reflux, 1 h;
99%. d) 2n NaOH, EtOH, reflux, 10 h; 90%. e) SOCl2, MeOH, 08, 1.5 h; 97%. f) Cl2CHOMe, SnCl4, CH2Cl2,
08 ! r.t., 2 h. g) HC(OMe)3, MeOH, NH4Cl, reflux, 2 h; 90%. h) CH2(COOH)2, pyridine, piperidine, reflux,
2 h; 81%. i) 2n KOH, MeOH, r.t., 2 h; 73%.
more trusted the highly reliable Rieche formylation of precursor 37. The latter was
accessible in a straightforward reaction cascade starting from easily available 2,3-
dimethoxybenzaldehyde (38). Reduction of 38 by means of NaBH4 ( ! 39), trans-
formation of the OH functionality into Cl ( ! 40) resulted, after substitution with
potassium cyanide, in nitrile 41. Hydrolysis under basic conditions gave acid 42, which
finally could be esterified to 37. Rieche formylation of 37 under standard conditions
resulted in the desired aldehyde 35 in good yield. Regioselectivity of this formylation
proved to be high again, but a small amount (7.5%) of regioisomer 18 was also
observed. On the one hand, aldehyde 35 was transformed into acetal 36, the important
intermediate for the subsequent aldol-type reaction. On the other hand, a Knoevenagel

Helvetica Chimica Acta Vol. 86 (2003)
351
condensation of 35 with malonic acid gave 43, which, after simple ester hydrolysis,
furnished 31, the above-mentioned skeleton of salvianolic acid D (33). This natural
compound
isolated from Salvia miltiorhizza
also contains the (2R)-3-(3,4-
dihydroxyphenyl)lactic acid residue.
For the ongoing synthesis of 30, acetal 36 was subjected to an aldol-type reaction
with veratrumaldehyde (9) (Scheme 6). Again, an equilibrium was reached quickly,
enabling the isolation of product 44 in a somewhat lower yield in comparison to the
above-mentioned aldol-type reactions. More conspicuously, 44 was obtained as a single
Scheme 6
OCH3
OCH3
a)
OH
36 + 9
OCH3
OCH3
H3CO
H3CO
O
OCH3
44
b)
OH
OH
OCH3
OH
OH
OCH3
O
OH
OCH3
H
OHC
O
OCH3
O
15%
OH
O
H
45
32
c)
OH
OH
OH
OCH3
OH
OH
O
OH
OH
OCH3
H
O
O
O
O
COOH
46
C
O
H
HOOC
H2C
COOH
34 salvianolic acid E
OH
OH
a) LDA, Et2O, À788, 1 h; 60%. b) BBr3, CH2Cl2, 08, 2 h; 42% (45). c) CH2(COOH)2, pyridine, piperidine, 1008,
2 h; 35%.

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Helvetica Chimica Acta Vol. 86 (2003)
diastereoisomer. Treatment of 44 with boron tribromide resulted in the formation of
the expected aryldihydrobenzofuran system 45. Due to the occurrence of a by-product
(see below), the yields were always lower than in former cases. Although an excess of
boron tribromide was used, one phenolic methyl ether was not cleaved under the
reaction conditions. The product 46 of a subsequent Knoevenagel condensation,
therefore, represented the monomethyl ether of przewalskinic acid (30). Structure 46
in particular the position of the remaining ether MeO group was secured by two-
dimensional NMR analysis. Clearly, with 46 in hand, a projected synthesis of
lithospermic acid (29) and salvianolic acid B (28) necessitates a one- or two-fold
esterification with (2R)-3-(3,4-dihydroxyphenyl)lactic acid. Once more, the intrinsic
diversification of the two carboxy groups in 46 greatly supports such a purpose.
In addition to that, the described cyclization also resulted in ca. 15% of the
interesting by-product 32. The latter was obviously produced by dehydration of 44 and
is surely utilizable as a key compound in the synthesis of salvianolic acid E (34). The
phenolic MeO group also present in 32 means that boron tribromide, at least under the
chosen reaction conditions, is not suitable for full deprotection. Larger amounts of 32
should be amenable from 44 in a well-directed synthesis.
Conclusions. In summary, it could be shown that boron tribromide is a highly
useful reagent for the simultaneous demethylation and cyclization within the context of
the synthesis of different hydroxylated aryldihydrobenzofuran systems that occur, e.g.,
in the structures of polyamine alkaloids or depsides. The presented methodology is
flexible enough to enable the construction of the different substitution patterns
essential for the total synthesis of such a natural product. Besides the simple reaction
conditions for the cyclization step, all starting materials are available by straight-
forward procedures from common inexpensive chemicals without needing any special
methods or reagents. Finally, the possibility to exchange both components of the aldol-
type reaction against other substituted ones, offers the chance for a substance library,
which may be of pharmaceutical interest regarding the physiological properties of the
original natural compounds.
We thank the analytical departments of our institute for all measurements, the Swiss National Science
Foundation for generous financial support, and, especially, Dr. A. Linden for the X-ray crystal-structure
determination.
Experimental Part
General. All commercially available reagents were used without further purification. Solvents were either
puriss. p.a. grade (Fluka) or were distilled prior to use. Reactions were normally not carried out under N2, unless
otherwise stated; they were monitored by TLC (Merck precoated silica gel plates 60 F254). All extracts were
dried (MgSO4) before evaporation, unless otherwise stated. Column chromatography (CC): silica gel 60 (230
400 mesh ASTM) from Merck. Melting points (M.p.): Mettler FP5. IR [cmÀ1]: in CHCl3 (Fluka for IR
spectroscopy); Perkin-Elmer 781. NMR Spectra: in CDCl3, except where noted, Bruker ARX-300 (1H at 300
and 13C at 75 MHz) or Bruker DRX-600 (1H at 600 and 13C at 150 MHz); chemical shifts d in ppm rel. to Me4Si as
internal standard; coupling constants J in Hz. MS: Finnigan SSQ-700 for chemical ionization (CI) with NH3,
Finnigan MAT-90 for electron impact (EI, 70 eV), and Finnigan TSQ-700 for electrospray ionization (ESI);
m/z (rel. intensity in %).
Methyl (2-Methoxyphenyl)acetate (11). To an ice-cooled soln. of (2-methoxyphenyl)acetic acid (10; 10.0 g,
60.0 mmol) in MeOH (100 ml), thionyl chloride (11.9 g, 7.25 ml, 0.1 mol) was added dropwise and slowly. After

Helvetica Chimica Acta Vol. 86 (2003)
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1 h stirring, evaporation yielded 11 (10.6 g, 98%). Colorless liquid, pure enough for the next step. IR: 3000w,
2950m, 2840w, 1730s, 1600m, 1590m, 1490s, 1460s, 1435s, 1340s, 1290s, 1250s, 1160s, 1110s, 1050w, 1030m.
1H-NMR (CDCl3): 7.24 (dt, J ˆ 9.7, 1.7, 1 H); 7.17 (dd, J ˆ 7.4, 1.7, 1 H); 6.92 (dd, J ˆ 7.4, 1.1, 1 H); 6.86 (dd, J ˆ
10.3, 2.0, 1 H); 3.81 (s, 3 H); 3.68( s, 3 H); 3.63 (s, 2 H). 13C-NMR (CDCl3): 172.2 (s); 157.4 (s); 130.7 (d); 128.4
‡
‡
(d); 122.9 (s); 120.4 (d); 110.4 (d); 5.4 (q); 51.7 (q); 35.6 (t). CI-MS: 198(100, [ M ‡ NH4] ), 181 (10, [M ‡ H] ).
Methyl (5-Formyl-2-methoxyphenyl)acetate (7). SnCl4 (22.8g, 10.3 ml, 87.0 mmol) was added to an ice-
cooled soln. of 11 (10.5 g, 58.0 mmol) in CH2Cl2 (150 ml). Then, dichloromethyl methyl ether (13.4 g, 10.3 ml,
116.0 mmol) was added dropwise within 30 min. Stirring was continued at r.t. for 90 min before the mixture was
hydrolyzed by careful pouring into ice-water. Extraction with CH2Cl2 and evaporation of the org. phase yielded
11.8g (98%) of 7. Oil, which was considered sufficiently pure for use in the next step. IR: 3000w, 2950w, 2840w,
2740w, 1735s, 1685s, 1605s, 1585m, 1500m, 1460w, 1440m, 1340m, 1325m, 1260s, 1170m, 1120m, 1025m, 910w.
1H-NMR (CDCl3): 9.87 (s, 1 H); 7.8 1 (dd, J ˆ 8.5, 2.1, 1 H); 7.73 (d, J ˆ 2.1, 1 H); 6.99 (d, J ˆ 8.5, 1 H); 3.91
(s, 3 H); 3.70 (s, 3 H); 3.68( s, 2 H). 13C-NMR (CDCl3): 190.7 (d); 171.4 (s); 162.5 (s); 132.1 (d); 131.8( d); 129.6
‡
‡
(s); 124.0 (s); 110.3 (d); 55.8( q); 51.9 (q); 35.4 (t). CI-MS: 226 (100, [M ‡ NH4] ), 209 (8, [M ‡ H] ).
Methyl [5-(Dimethoxymethyl)-2-methoxyphenyl]acetate (12). A mixture of 7 (11.0 g, 53.0 mmol),
trimethyl orthoformate (11.3 g, 11.6 ml, 106.0 mmol) and a cat. amount (ca. 0.1 g) of NH4Cl in MeOH
(100 ml) was refluxed for 2 h. After cooling to r.t., the mixture was poured into ice-cooled aq. 2n NaOH and
extracted quickly with Et2O. Evaporation gave 11.9 g (88%) of 12. Yellowish oil of sufficient purity. IR: 2995m,
2950s, 2900m, 2840m, 1735s, 1615m, 1500s, 1460m, 1435s, 1405w, 1340s, 1310w, 1255s, 1160s, 1125m, 1100s,
1050m, 990w. 1H-NMR (CDCl3): 7.32 (dd, J ˆ 8.4, 2.2, 1 H); 7.26 (d, J ˆ 2.2, 1 H); 6.85 (d, J ˆ 8.4, 1 H); 5.34
(s, 1 H); 3.80 (s, 3 H); 3.67 (s, 3 H); 3.63 (s, 2 H); 3.30 (s, 6 H). 13C-NMR (CDCl3): 172.0 (s); 157.5 (s); 130.1 (s);
129.3 (d); 126.8( d); 122.7 (s); 110.0 (d); 102.8( d); 55.4 (q); 52.4 (q); 51.7 (2q); 35.6 (t). CI-MS: 223 ([M À
‡
MeOH ‡ H] )3).
Methyl 2-(5-Formyl-2-methoxyphenyl)-3-hydroxy-3-(4-methoxyphenyl)propanoate (13). A freshly pre-
pared LDA soln. (iPr2NH (0.4 ml) and 1.6m BuLi (1.8ml) in abs. Et 2O (10 ml)) was cooled to À788, and then 12
(0.48g, 1.90 mmol) was added. After 10 min, anisaldehyde ( 8; 0.26 g, 1.90 mmol) was introduced and the
mixture stirred at À788 for 30 min. The cold soln. was quenched by addition of dil. aq. HCl soln. and extracted
with Et2O. Evaporation and separation of 13 from starting material was achieved by CC (SiO2, hexane/AcOEt
2 :1 ! 1:1): 13 (0.57 g, 77%). Colorless oil. IR: 3520 (br.), 3020w, 3000w, 2950m, 2900w, 2840m, 2740w, 1730s,
1590s, 1600s, 1580m, 1500s, 1460m, 1440m, 1370w, 1300w, 1260s, 1105m, 1025m, 8 30m. 1H-NMR (CDCl3)4):
isomer A: 9.88 (s, 1 H); 7.93 (d, J ˆ 2.1, 1 H); 7.82 (dd, J ˆ 8.6, 2.1, 1 H); 7.11 (d, J ˆ 8.7, 2 H); 6.89 (d, J ˆ 8.6,
1 H); 6.77 (d, J ˆ 8.7, 2 H); 5.40 (d, J ˆ 6.0, 1 H); 4.51 (d, J ˆ 6.0, 1 H); 3.76 (s, 3 H); 3.68( s, 3 H); 3.61 (s, 3 H);
isomer B: 9.79 (s, 1 H); 7.70 (dd, J ˆ 8.5, 2.1, 1 H); 7.65 (d, J ˆ 2.1, 1 H); 7.02 (d, J ˆ 6.7, 2 H); 6.81 (d, J ˆ 8.5,
1 H); 6.68( d, J ˆ 6.7, 2 H); 5.15 (d, J ˆ 8.8, 1 H); 4.35 (d, J ˆ 8.8, 1 H); 3.71 (s, 9 H). 13C-NMR (CDCl3)5): 190.7
(d); 190.5 (d); 173.9 (s); 173.0 (s); 162.2 (s); 161.4 (s); 159.0 (s); 158.9 (s); 133.1 (s); 132.7 (s); 132.0 (d); 131.2
(d); 131.1 (d); 130.9 (d); 129.6 (s); 127.6 (d); 127.5 (d); 125.5 (s); 124.2 (s); 113.3 (d); 113.1 (d); 110.7 (d); 74.8
‡
(d); 73.7 (d); 55.7 (q); 55.1 (q); 52.2 (d); 52.0 (q); 50.5 (d). CI-MS: 362 (19, [M ‡ NH4] ), 344 (46, [M À H2O ‡
‡
‡
NH4] ), 327 (30, [M À H2O ‡ H] ).
Methyl 3-(3,4-Dimethoxyphenyl)-2-(5-formyl-2-methoxyphenyl)-3-hydroxypropanoate (14). As described
for 13, with 7 (0.56 g, 19.0 mmol) and veratrumaldehyde (9; 0.36 g, 2.19 mmol). CC (SiO2, hexane/AcOEt 1 :1)
yielded 14 (0.63 g, 77%). Colorless solid (mixture of two diastereoisomers). IR: 3500 (br.), 3020w, 3000w,
2950m, 2840m, 2740w, 1740s, 1690s, 1600s, 1580m, 1500m, 1460m, 1435m, 1320w, 1260s, 1150w, 1140m, 1100w,
1025m, 910s, 8 55w. 1H-NMR (CDCl3): 9.87 (s); 9.79 (s); 7.97 (d); 7.80 (dd); 7.71 7.68( m); 6.88 (d); 6.83 6.59
(m); 5.39 (d); 5.15 (d); 4.50 (d); 4.38( d); 3.83 3.44 (8s). 13C-NMR (CDCl3): 90.8( d); 190.5 (d); 173.8( s); 173.0
(s); 162.3 (s); 161.5 (s); 148.4 (s); 148.3 (s); 133.6 (s); 133.1 (s); 132.0 (d); 131.2 (d); 131.0 (d); 130.9 (d); 129.5
(s); 129.4 (s); 125.4 (s); 124.2 (s); 119.0 (d); 118.6 (d); 110.65 (d); 110.56 (d); 110.51 (d); 110.27 (d); 109.57 (d);
‡
109.48( d); 75.1 (d); 73.7 (d); 55.7 (q); 55.60 (q); 52.2 (q); 52.1 (q); 52.0 (d); 50.4 (d). ESI-MS: 397 ([M ‡ Na] ).
‡
‡
3
)
The loss of MeOH from the [M ‡ H] or [M ‡ NH4] ion under the CI-measurement conditions proved to
be very characteristic for such dimethoxy acetals. Without exception, all measured compounds of this type
showed such a behavior, whereas for none of them, a [M ‡ NH4] or [M ‡ H] signal could be observed (cf.
‡
‡
also [18]).
4
5
)
Product 13 was obtained as a mixture of two diastereoisomers A and B in a ratio of ca. 1:2 (see General
Part). Separation of the 1H-NMR signals of these isomers was possible with the help of signal integration.
No separation of the 13C-NMR signals of the diastereoisomers A and B was possible.
)

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Helvetica Chimica Acta Vol. 86 (2003)
Methyl trans-5-Formyl-2,3-dihydro-2-(4-hydroxyphenyl)benzofuran-3-carboxylate (15). To an ice-cooled
soln. of 13 (0.13 g, 0.38mmol) in CH 2Cl2 (10 ml), a freshly prepared soln. of BBr3 (0.95 g, 0.36 ml, 3.8mmol) in
CH2Cl2 (5 ml; Merck puriss.) was added dropwise ( ! rapid precipitation of a brown solid). The temp. was
raised to r.t. within 2 h before the mixture was carefully quenched with MeOH (vigorous generation of HBr!).
Dilution with aq. NaCl soln. and extraction with CH2Cl2 yielded, after evaporation and CC (SiO2, hexane/
AcOEt 1:1), 15 (77 mg, 68%). Small yellow crystals. IR: 3600m, 3500 3100 (br.), 3020w, 2960w, 2840w, 2740w,
1740s, 1690s, 1600s, 1515m, 1485m, 1440m, 1325w, 1280w, 1245s, 1170s, 1105m, 1035w, 970w, 940w, 920w, 8 30m,
630w. 1H-NMR (CDCl3): 9.86 (s, 1 H); 7.94 (d, J ˆ 1.5, 1 H); 7.80 (dd, J ˆ 8.3, 1.6, 1 H); 7.25 (d, J ˆ 8.5, 2 H); 6.99
(d, J ˆ 8.3, 1 H); 6.85 (d, J ˆ 8.6, 2 H); 6.15 (d, J ˆ 7.5, 1 H); 5.81 (br. s, 1 H); 4.32 (d, J ˆ 7.5, 1 H); 3.84 (s, 3 H).
13C-NMR (CDCl3): 190.6 (d); 170.5 (s); 164.4 (s); 156.3 (s); 134.0 (d); 131.4 (s); 130.6 (s); 127.4 (d); 126.8( d);
‡
‡
125.5 (s); 115.7 (d); 110.3 (d); 87.1 (d); 54.5 (d); 52.9 (q). CI-MS: 316 (100, [M ‡ NH4] ), 299 (36, [M ‡ H] ).
Methyl trans-2-(3,4-Dihydroxyphenyl)-5-formyl-2,3-dihydrobenzofuran-3-carboxylate (16). As described
for 15, with 14 (0.36 g, 0.96 mmol) and BBr3 (2.41 g, 0.91 ml, 9.60 mmol). CC (SiO2, hexane/AcOEt 2 :1) gave 16
(0.27 g, 90%). Yellow oil, which was crystallized for X-ray-analysis from CDCl36). M.p. 116 1178 (CDCl3). IR:
3540m, 3200(br.), 2980w, 2950w, 2840w, 1730s, 1685s, 1600s, 1520w, 1480w, 1440m, 1370m, 1220s, 1105m, 1040w,
975w, 940w, 915w. 1H-NMR ((D6)DMSO): 9.87 (s, 1 H); 9.0 (br., 2 H); 7.89 7.84 (m, 2 H); 7.08( d, J ˆ 8.2, 1 H);
6.75 6.66 (m, 3 H); 5.96 (d, J ˆ 6.8, 1 H); 4.50 (d, J ˆ 6.8, 1 H); 3.75 (s, 3 H). 13C-NMR ((D6)DMSO): 191.0
(d); 170.6 (s); 163.8( s); 145.9 (s); 145.4 (s); 133.5 (d); 130.4 (s); 130.1 (s); 126.7 (d); 126.0 (s); 117.4 (d); 115.5
‡
‡
(d); 113.3 (d); 109.9 (d); 87.2 (d); 53.4 (d); 52.7 (q). CI-MS: 332 (100, [M ‡ NH4] ), 315 (55, [M ‡ H] ).
Methyl trans-5-[(1E)-2-Carboxyethenyl]-2,3-dihydro-2-(4-hydroxyphenyl)benzofuran-3-carboxylate (5).
To a soln. of 15 (52 mg, 0.17 mmol) in pyridine (5 ml) were added malonic acid (36 mg, 0.35 mmol) and two
drops of piperidine. The mixture was refluxed for 2 h and then poured into an excess of dil. aq. HCl soln.
Extraction with AcOEt and evaporation gave 5 (57 mg, 97%). Yellow solid. IR: 3590m, 3500 2400(br.), 1735s,
1685s, 1630m, 1600s, 1510m, 1485s, 1435s, 1370w, 1330w, 1200s, 1170s, 1110m, 1035w, 98 0m, 910m, 8 65w, 8 35m,
820m. 1H-NMR (CDCl3): 9.30 (br., 2 H); 7.76 (d, J ˆ 15.9, 1 H); 7.59 (d, J ˆ 1.7, 1 H); 7.45 (dd, J ˆ 8.3, 1.7, 1 H);
7.26 (d, J ˆ 8.5, 2 H); 6.90 (d, J ˆ 8.3, 1 H); 6.84 (d, J ˆ 8.6, 2 H); 6.33 (d, J ˆ 15.9, 1 H); 6.10 (d, J ˆ 7.5, 1 H);
4.28( d, J ˆ 7.5, 1 H); 3.85 (s, 3 H). 13C-NMR (CDCl3): 172.0 (s); 170.8( s); 161.4 (s); 156.1 (s); 146.6 (d); 131.8
(s); 131.1 (d); 127.4 (s ‡ d); 125.1 (s ‡ d); 115.6 (d); 114.5 (d); 110.3 (d); 86.4 (d); 54.9 (d); 52.8( q). CI-MS: 358
‡
‡
‡
‡
(100, [M ‡ NH4] ), 341 (64, [M ‡ H] ), 340 (18, [M À H2O ‡ NH4] ), 323 (86, [M À H2O ‡ H] ), 297 (35,
‡
[M À CO2 ‡ H] ).
3-Methoxy-4-[(prop-2-enyl)oxy]benzaldehyde (ˆO-Allylvanillin; 20). To vanillin (19, 20.0 g, 0.13 mol) in
acetone (150 ml), allyl bromide (19.90 g, 13.9 ml, 0.16 mol) and K2CO3 (27.25 g, 0.20 mol) were added. Then the
mixture was refluxed for 8h. After pouring into H 2O and extraction with Et2O, the org. phase was washed with
dil. aq. NaOH soln. and evaporated: 20 (22.5 g, 90%). Slightly yellow oil. IR: 3080w, 3030w, 3000w, 2960w,
2940m, 2840m, 2740w, 1675s, 1595s, 1585s, 1500s, 1460s, 1420s, 1390m, 1360w, 1335w, 1270s, 1160s, 1130s, 1030m,
995s, 935m, 8 7m0 . 1H-NMR (CDCl3): 9.85 (s, 1 H); 7.44 7.41 (m, 2 H); 6.98( d, J ˆ 8.7, 1 H); 6.15 6.02
(m, 1 H); 5.48 5.41 ( m, 2 H); 4.70 (dt, J ˆ 5.4, 1.5, 2 H); 3.94 (s, 3 H). 13C-NMR (CDCl3): 190.7 (d); 153.4 (s);
149.8( s); 132.1 (d); 130.1 (s); 126.4 (d); 118.6 (t); 111.9 (d); 109.3 (d); 69.7 (t); 55.9 (q). CI-MS: 210 (11, [M ‡
‡
‡
NH4] ), 193 (100, [M ‡ H] ).
4-Hydroxy-3-methoxy-5-(prop-2-enyl)benzaldehyde (21). A soln. of 20 (19.7 g, 0.10 mol) in mesitylene
(75 ml) was refluxed for 20 h. The cooled soln. was poured into aq. 2n NaOH and washed with Et2O twice. The
org. phase was discarded and the ice-cooled aq. phase acidified with aq. conc. HCl soln. and extracted with
AcOEt. Evaporation yielded 21 (17.4 g, 88%). Orange oil, which was considered to be sufficiently pure for the
next step. IR: 3520s, 3080w, 3000w, 2970w, 2940w, 2840w, 2730w, 1680s, 1640w, 1595s, 1490m, 1460m, 1435m,
1400m, 1370w, 1300s, 1140s, 1105w, 1070m, 995w, 950w, 920w, 8 60w. 1H-NMR (CDCl3): 9.80 (s, 1 H); 7.31
(s, 2 H); 6.39 (s, 1 H); 6.07 5.94 (m, 1 H); 5.15 5.18( m, 2 H); 3.95 (s, 3 H); 3.46 (dt, J ˆ 6.6, 1.4, 2 H).
13C-NMR (CDCl3): 191.0 (d); 149.3 (s); 146.8( s); 135.4 (d); 129.0 (s); 127.8( d); 126.0 (s); 116.2 (t); 107.0 (d);
56.1 (q); 33.3 (t).
3,4-Dimethoxy-5-(prop-2-enyl)benzaldehyde (22). K2CO3 (10.1 g, 72.8mmol) and MeI (7.75 g, 3.4 ml,
54.6 mmol) were added to a soln. of 21 (7.0 g, 36.4 mmol) in DMF (40 ml). The mixture was stirred at r.t. for 8h,
then taken up in H2O, and extracted with Et2O. Washing the org. phase with dil. aq. NaOH soln. and evaporation
gave 22 (6.91 g, 92%). Colorless liquid. IR: 3070w, 2940m, 2830m, 2740w, 1690s, 1635w, 1580s, 1480m, 1460m,
1
1420m, 1380s, 1330w, 1300s, 1220w, 1140s, 1110w, 1070m, 1000s, 915m, 8 60m. H-NMR (CDCl3): 9.87 (s, 1 H);
6
)
See Fig. 1 and Table.

Helvetica Chimica Acta Vol. 86 (2003)
355
7.33 (d, J ˆ 1.9, 1 H); 7.31 (d, J ˆ 1.9, 1 H); 6.04 5.91 (m, 1 H); 5.12 5.05 (m, 2 H); 3.92 (s, 3 H); 3.90 (s, 3 H);
3.46 (dt, J ˆ 6.5, 1.4, 2 H). 13C-NMR (CDCl3): 191.2 (d); 153.2 (s); 152.5 (s); 136.2 (d); 134.2 (s); 132.2 (s);
‡
126.4 (d); 116.2 (t); 109.0 (d); 60.6 (q); 55.8( q); 33.9 (t). CI-MS: 224 (34, [M ‡ NH4] ), 207 (100,
‡
[M ‡ H] ).
5-(Dimethoxymethyl)-1,2-dimethoxy-3-(prop-2-enyl)benzene (23). As described for 12, with 22 (2.66 g,
12.9 mmol): 23 (3.1 g, 95%). Colorless liquid. IR: 3070w, 2940s, 2900w, 2820m, 1635w, 1590s, 1490s, 1460s,
1420m, 1355s, 1300s, 1230w, 1210w, 1190m, 1150s, 1100s, 1070m, 1050s, 1010m, 990m, 910m, 8 55m. 1H-NMR
((D6)benzene): 7.12 (d, J ˆ 1.9, 1 H); 7.05 (d, J ˆ 1.9, 1 H); 6.06 5.97 (m, 1 H); 5.35 (s, 1 H); 5.10 4.99
(m, 2 H); 3.73 (s, 3 H); 3.47 (dt, J ˆ 6.5, 1.4, 2 H); 3.39 (s, 3 H); 3.19 (s, 6 H). 13C-NMR ((D6)benzene): 153.3
(s); 147.9 (s); 137.9 (d); 134.4 (s); 133.7 (s); 121.1 (d); 115.6 (t); 109.9 (d); 103.1 (d); 60.3 (q); 55.4 (q); 52.1 (2q);
34.7 (t).
(5-Formyl-2,3-dimethoxyphenyl)acetic Acid (24). To 23 (3.90 g, 15.5 mmol) in tBuOH (25 ml) was added a
soln. of K2CO3 (6.40 g, 46.0 mmol) in H2O (50 ml). To the resulting suspension were added NaIO4 (13.6 g,
46.0 mmol) and KMnO4 (2.0 g, 12.4 mmol). The mixture started to warm and was stirred for 4 h at r.t.
The mixture was washed with AcOEt and this org. phase discarded. The aq. phase was acidified with dil.
aq. HCl soln. and again extracted with AcOEt exhaustively. Evaporation yielded 24 (1.80 g, 52%). Slightly
yellowish oil. IR: 3600 2400 (br.), 2940w, 2840w, 1710s, 1690s, 1590s, 1485m, 1460m, 1430w, 1385m, 1300s,
1140s, 1090s, 1000s, 8 60w. 1H-NMR (CHCl3): 9.86 (s, 1 H); 8.4 (br., 1 H); 7.41 (d, J ˆ 1.9, 1 H); 7.36 (d, J ˆ 1.9,
1 H); 3.94 (s, 3 H); 3.92 (s, 3 H); 3.74 (s, 2 H). 13C-NMR (CHCl3): 191.1 (d); 176.6 (s); 152.9 (s); 152.8( s);
‡
131.9 (s); 128.0 (s); 126.9 (d); 110.6 (d); 60.6 (q); 55.8( q); 35.4 (t). CI-MS: 242 (100, [M ‡ NH4] ), 225 (6, [M ‡
‡
H] ).
Methyl (5-Formyl-2,3-dimethoxyphenyl)acetate (18). As described for 11, with 24 (2.13 g, 9.50 mmol): 1.69 g
(75%) of 18. Colorless oil. IR: 3000w, 2940w, 2840w, 1735s, 1690s, 1590s, 1485w, 1460m, 1430m, 1390m, 1350w,
1300s, 1220w, 1140s, 1090m, 1010m, 1000m. 1H-NMR (CHCl3): 9.87 (s, 1 H); 7.40 (d, J ˆ 1.9, 1 H); 7.36 (d, J ˆ 1.9,
1 H); 3.92 (2s, 6 H); 3.72 (2s, 5 H). 13C-NMR (CHCl3): 190.8( d); 171.4 (s); 153.0 (s); 152.7 (s); 132.0 (s); 128.6
‡
‡
(s); 126.9 (d); 110.3 (d); 60.6 (q); 55.8( q); 52.0 (q); 35.4 (t). CI-MS: 256 (100, [M ‡ NH4] ), 239 (15, [M ‡ H] ).
Methyl [5-(Dimethoxymethyl)-2,3-dimethoxyphenyl]acetate (25). As described for 12, with 18 (1.69 g,
7.10 mmol): 1.51 g (75%) of 25. Yellow oil. IR: 2995m, 2940s, 2830s, 1735s, 1595s, 1490s, 1460s, 1430m, 1360s,
1310w, 1270w, 1150s, 1090s, 1050s, 1000s, 950w, 8 55m. 1H-NMR ((D6)benzene): 7.11 (d, J ˆ 1.9, 1 H); 7.05 (d, J ˆ
1.9, 1 H); 5.32 (s, 1 H); 3.78( s, 3 H); 3.62 (s, 2 H); 3.35 (s, 3 H); 3.34 (s, 3 H); 3.18( s, 6 H). 13C-NMR
((D6)benzene): 171.6 (s); 153.1 (s); 148.2 (s); 134.3 (d); 128.6 (s); 121.9 (d); 110.8( t); 102.9 (d); 60.2 (q); 55.4
‡
(q); 52.1 (2q); 51.4 (q); 36.0 (t). CI-MS: 253 ([M À MeOH ‡ H] ).
Methyl 2-[5-(Dimethoxymethyl)-2,3-dimethoxyphenyl]-3-hydroxy-3-(4-methoxyphenyl)propanoate (26).
As described for 13, with 25 (1.51 g, 5.31 mmol) and anisaldehyde (8; 0.82 g, 0.73 ml, 6.0 mmol). CC (SiO2,
hexane/AcOEt 2 :1 ! 1:1) yielded 1.65 g (73%) of 26. Mixture of two diastereoisomers. IR: 3500 (br.), 3020w,
2980m, 2940s, 2900m, 2830s, 1725s, 1610s, 1590s, 1510m, 1485m, 1460s, 1430m, 1350s, 1300s, 1240s, 1170w, 1140m,
1100s, 1050s, 1000s, 940w, 910w, 8 60m, 8 30s. 1H-NMR ((D6)benzene)7): isomer A: 7.62 (d, J ˆ 1.8, 1 H); 7.33
(d, J ˆ 8.6, 2 H); 7.06 (d, J ˆ 1.8, 1 H); 6.72 (d, J ˆ 8.7, 2 H); 5.48 (d, overlap with isomer B, 1 H); 5.34 (s, 1 H);
4.74 (d, J ˆ 7.2, 1 H); 3.74 (s, 3 H); 3.35 3.10 (4s, overlap with isomer B, 15 H); 2.81 (br. s, 1 H); isomer B: 7.25
(d, J ˆ 1.8, 1 H); 7.21 (d, J ˆ 8.6, 2 H); 6.92 (d, J ˆ 1.8, 1 H); 6.59 (d, J ˆ 8.7, 2 H); 5.48 (d, overlap with isomer A,
1 H); 5.25 (s, 1 H); 4.59 (d, J ˆ 9.4, 1 H); 3.62 (br. s, 1 H); 3.59 (s, 3 H); 3.35 3.10 (4s, overlap with isomer A,
15 H). 13C-NMR ((D6)benzene): 174.6 (s); 173.3 (s); 1597 (s); 159.5 (s); 153.2 (s); 153.0 (s); 147.7 (s); 134.9 (s);
134.4 (s); 134.1 (s); 130.0 (s); 129.6 (s); 128.3 (d); 128.2 (d); 120.4 (d); 120.3 (d); 113.7 (d); 113.5 (d); 110.7 (d);
110.6 (d); 103.2 (d); 102.9 (d); 75.6 (d); 74.8( d); 60.3 (q); 60.1 (q); 55.2 (q); 54.6 (q); 53.9 (d); 52.6 (d); 52.1 (q);
‡
‡
51.6 (q). CI-MS: 389 (100, [M À MeOH ‡ H] ), 371 (7, [M À MeOH À H2O ‡ H] ), 340 (23, [M À MeOH À
‡
MeO À H2O ‡ H] ).
Methyl trans-5-Formyl-2,3-dihydro-7-hydroxy-2-(4-hydroxyphenyl)benzofuran-3-carboxylate (17). As de-
scribed for 15, with 26 (0.14 g, 0.33 mmol) and BBr3 (0.84 g, 0.32 ml, 3.30 mmol). CC (SiO2, hexane/AcOEt 1 :1)
yielded 85 mg (82%) of 17. Yellow foam. IR: 3580m, 3300 (br.), 2950w, 2840w, 1740s, 1690s, 1600s, 1490m,
1450w, 1435w, 1350s, 1270s, 1170s, 1120s, 1035w, 995w, 940w, 910w, 8 70w, 8 30w. 1H-NMR ((D6)acetone): 9.83
(s, 1 H); 8.69 (s, 1 H); 8.52 (s, 1 H); 7.49 (m, 1 H); 7.38( m, 1 H); 7.31 (d, J ˆ 8.6, 2 H); 6.88 (d, J ˆ 8.6, 2 H); 6.11
7
)
Product 26 was obtained as a mixture of two diastereoisomers A and B in a ratio of ca. 1:2 (see General
Part). Separation of the 1H-NMR signals of these isomers was at least partly possible with the help of
signal integration. No separation was obtained for the 13C-NMR signals.

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Helvetica Chimica Acta Vol. 86 (2003)
(d, J ˆ 7.5, 1 H); 4.48( d, J ˆ 7.4, 1 H); 3.81 (s, 3 H). 13C-NMR ((D6)acetone): 191.0 (d); 171.5 (s); 158.9 (s); 153.2
(s); 143.0 (s); 132.8( s); 131.5 (s); 128.7 (d); 127.6 (s); 120.1 (d); 118.3 (d); 116.4 (d); 88.5 (d); 55.7 (d); 53.1 (q).
‡
‡
CI-MS: 332 (100, [M ‡ NH4] ), 315 (65, [M ‡ H] ).
Methyl trans-5-(2-Carboxyethenyl)-2,3-dihydro-7-hydroxy-2-(4-hydroxyphenyl)benzofuran-3-carboxylate
(27). As described for 5, with 17 (0.11 g, 0.36 mmol) and malonic acid (0.11 g, 1.07 mmol): 0.12 g (92%) of
27. Yellow oil. IR (KBr): 3500 2300 (br.), 2954w, 1683s, 1603s, 1516m, 1495m, 1445m, 1340s, 1274s, 1210s, 1170s,
1137s, 1073w, 978m, 914w, 8 53w, 8 35m, 752w. 1H-NMR ((D6)acetone): 8.50 (br., 2 H); 7.58 (d, J ˆ 15.9, 1 H); 7.31
(d, J ˆ 8.5, 2 H); 7.21 (d, J ˆ 1.7, 1 H); 7.14 (d, J ˆ 1.7, 1 H); 6.88 (d, J ˆ 8.6, 2 H); 6.33 (d, J ˆ 15.9, 1 H); 6.03
(d, J ˆ 7.6, 1 H); 4.40 (d, J ˆ 7.6, 1 H); 3.81 (s, 3 H). 13C-NMR ((D6)acetone): 171.7 (s); 168.0 (s); 158.7 (s); 150.0
(s); 145.6 (d); 142.6 (s); 131.8( s); 129.6 (s); 128.6 (d); 127.5 (s); 117.7 (d); 117.4 (d); 116.6 (d); 116.4 (d); 88.0 (d);
‡
‡
56.2 (d); 53.0 (q). ESI-MS: 357 (100, [M ‡ H] ), 339 (45, [M À H2O ‡ H] ).
(2,3-Dimethoxyphenyl)methanol (39). To a soln. of 2,3-dimethoxybenzaldehyde (38; 34.0 g, 0.21 mmol) in
MeOH (120 ml) was carefully added NaBH4 (4.7 g, 0.124 mmol) in some portions. Then the mixture was stirred
for 1 h at r.t. After evaporation, the residue was diluted with H2O. Extraction with CH2Cl2, washing with
H2O, and evaporation yielded 35 (34.0 g, 99%). Slightly brownish liquid. IR: 3600m, 3450 (br.), 3020w, 2990w,
2960w, 2940s, 2840m, 1600w, 1585s, 1480s, 1430m, 1390m, 1305m, 1270s, 1170m, 1080s, 1010s, 960m, 900w.
1H-NMR (CHCl3): 7.06 7.01 (m, 1 H); 6.94 6.85 (m, 2 H); 4.68( s, 2 H); 3.87 (s, 3 H); 3.86 (s, 3 H); 2.37
(s, 1 H). 13C-NMR (CHCl3): 152.4 (s); 146.9 (s); 134.5 (s); 124.1 (d); 120.5 (d); 112.1 (d); 61.2 (t); 60.7 (q);
55.7 (q).
1-(Chloromethyl)-2,3-dimethoxybenzene (40). To a soln. of 39 (32.2 g, 0.19 mol) in CHCl3 (200 ml) were
added pyridine (6 ml) and then dropwise thionyl chloride (42.6 g, 26.0 ml, 0.36 mol) (caution: strongly
exothermic reaction!). After cooling to r.t., the mixture was diluted with H2O and extracted with CH2Cl2.
Subsequent washing of the org. phase with H2O and aq. NaHCO3 soln. yielded, after evaporation, 40 (33.9 g,
95%). Slightly brownish liquid. IR: 3020w, 2990w, 2960w, 2940m, 2900w, 2840m, 1590s, 1480s, 1460w, 1430m,
1310m, 1270s, 1170w, 1150w, 1080s, 1000s, 945m. 1H-NMR (CHCl3): 7.07 7.02 (m, 1 H); 6.99 6.95 (m, 1 H);
6.91 6.88 (m, 1 H); 4.65 (s, 2 H); 3.92 (s, 3 H); 3.86 (s, 3 H). 13C-NMR (CHCl3): 152.7 (s); 147.4 (s); 131.5 (s);
124.1 (d); 122.1 (d); 112.9 (d); 61.1 (q); 55.7 (q); 41.0 (t).
(2,3-Dimethoxyphenyl)acetonitrile (41). To a hot soln. of KCN (10.25 g, 0.16 mol) in H2O (20 ml) was
added 40 (24.9 g, 0.13 mol) in EtOH (50 ml). The mixture was refluxed for 1 h, poured in ice-water, and
extracted with CH2Cl2. Evaporation gave 41 (23.4 g, 99%). Thin oil. IR: 2990w, 2960w, 2940m, 2900w, 2840m,
2250w, 1600m, 1590m, 1480s, 1460w, 1430m, 1410w, 1310w, 1270s, 1170m, 1075s, 1000s. 1H-NMR (CHCl3): 7.08
7.03 (m, 1 H); 6.96 6.89 (m, 2 H); 3.91 (s, 3 H); 3.8 7 (s, 3 H); 3.71 (s, 2 H). 13C-NMR (CHCl3): 152.6 (s); 146.7
(s); 124.2 (d); 124.1 (s); 120.9 (d); 118.1 (s); 112.7 (d); 60.5 (q); 55.7 (q); 18.4 (t).
(2,3-Dimethoxyphenyl)acetic Acid (42). A mixture of 41 (10.0 g, 56.4 mmol) in H2O (40 ml) and aq. 2n
NaOH (160 ml) was refluxed for 10 h. After concentration to half of the volume, the mixture was washed once
with Et2O and the org. phase was discarded. The aq. phase was acidified with conc. aq. HCl soln. and extracted
with AcOEt. Washing with H2O and evaporation yielded 42 (9.90 g, 90%). Oil. IR: 3500 2400 (br.), 2940m,
2840m, 1710s, 1600w, 1590m, 1470s, 1430w, 1400w, 1270s, 1170m, 1080s, 1040w, 1005s, 955m. 1H-NMR (CHCl3):
10.5 (br., 1 H); 7.03 7.00 (m, 1 H); 6.98 6.80 ( m, 2 H); 3.85 (s, 3 H); 3.84 (s, 3 H); 3.68( s, 2 H). 13C-NMR
(CHCl3): 177.8( s); 152.6 (s); 147.3 (s); 127.6 (s); 123.8( d); 122.5 (d); 111.9 (d); 60.4 (q); 55.6 (q); 35.4 (t).
Methyl (2,3-Dimethoxyphenyl)acetate (37). As described for 11, with 42 (9.1 g, 46.4 mmol) and thionyl
chloride (8.27 g, 5.0 ml, 69.6 mmol): 9.5 g (97%) of 37. Colorless liquid. IR: 3020w, 3000m, 2940m, 2900w,
2840m, 1735s, 1600m, 1590m, 1475s, 1430s, 1340m, 1275s, 1160s, 1080s, 1010s, 955w. 1H-NMR (CHCl3): 7.03 6.97
(m, 1 H); 6.86 6.80 (m, 2 H); 3.85 (s, 3 H); 3.82 (s, 3 H); 3.69 (s, 3 H); 3.66 (s, 2 H). 13C-NMR (CHCl3): 172.0
(s); 152.6 (s); 147.3 (s); 128.2 (s); 123.7 (d); 122.5 (d); 111.7 (d); 60.4 (q); 55.6 (q); 51.8( q); 35.4 (t).
Methyl (6-Formyl-2,3-dimethoxyphenyl)acetate (35). As described for 7, with 37 (1.0 g, 4.76 mmol),
SnCl4 (1.86 g, 0.84 ml, 7.13 mmol), and dichloromethyl methyl ether (1.09 g, 0.84 ml, 9.5 mmol). CC (SiO2,
hexane/AcOEt 3 :1) yielded 35 (0.85 g, 75%). Oil. IR: 2940w, 2840w, 2740w, 1735s, 1690s, 1595m, 1570m,
1490w, 1460m, 1430w, 1340w, 1280s, 1170w, 1090s, 1005m, 98 0m. 1H-NMR (CHCl3): 9.92 (s, 1 H); 7.57 (d, J ˆ 8.5,
1 H); 7.00 (d, J ˆ 8.5, 1 H); 4.18 (s, 2 H); 3.96 (s, 3 H); 3.82 (s, 3 H); 3.71 (s, 3 H). 13C-NMR (CHCl3):
191.6 (d); 171.6 (s); 157.2 (s); 148.0 (s); 132.3 (d); 129.7 (s); 128.3 (s); 110.3 (d); 60.8( q); 55.8( q); 51.8( q);
30.9 (t).
Methyl [6-(Dimethoxymethyl)-2,3-dimethoxyphenyl]acetate (36). As described for 12, with 35 (0.76 g,
3.19 mmol) and trimethyl orthoformate (1.02 g, 1.05 ml, 9.6 mmol): 0.82 g (90%) of 36. Yellow oil. IR: 2995w,
2940m, 2840m, 1730s, 1600m, 1490m, 1455m, 1435w, 1420w, 1375w, 1340m, 1310m, 1275s, 1160m, 1110m, 1080s,
1045s, 1010w, 990w, 960w. 1H-NMR ((D6)benzene): 7.42 (d, J ˆ 8.5, 1 H); 6.54 (d, J ˆ 8.5, 1 H); 5.39 (s, 1 H); 4.07

Helvetica Chimica Acta Vol. 86 (2003)
357
(s, 2 H); 3.82 (s, 3 H); 3.38( s, 3 H); 3.28( s, 3 H); 3.15 (s, 6 H). 13C-NMR ((D6)benzene): 171.9 (s); 153.2 (s);
148.8 (s); 130.0 (s); 123.2 (d); 110.8( d); 102.3 (d); 60.2 (q); 55.2 (q); 52.4 (2q); 51.3 (q); 31.8( t)8). CI-MS: 253
‡
([M À CH3OH ‡ H] ).
3-{3,4-Dimethoxy-2-[(methoxycarbonyl)methyl]phenyl}prop-2-enoic Acid (43). As described for 5, with 35
(0.20 g, 0.84 mmol) and malonic acid (0.20 g, 1.9 mmol): 0.19 g (81%) of 43. Powder. IR: 3500 2400 (br.),
2940w, 2840w, 1735s, 1690s, 1630m, 1595s, 1490m, 1460w, 1435w, 1275s, 1165w, 1125w, 1080m, 1040w, 1005w,
980w. 1H-NMR (CHCl3): 7.93 (d, J ˆ 15.6, 1 H); 7.41 (d, J ˆ 8.7, 1 H); 6.90 (d, J ˆ 8.7, 1 H); 6.28 (d, J ˆ 15.6,
1 H); 4.90 (br., 1 H); 3.91 (s, 3 H); 3.88 (s, 2 H); 3.83 (s, 3 H); 3.71 (s, 3 H). 13C-NMR (CHCl3): 171.5 (2s); 154.2
(s); 147.5 (s); 143.5 (d); 128.6 (s); 126.8( s); 123.0 (d); 117.4 (d); 111.5 (d); 60.6 (q); 55.7 (q); 52.1 (q); 31.6 (t). CI-
‡
‡
‡
MS: 298(100, [ M ‡ NH4] ), 280 (32, [M À H2O ‡ NH4] ), 263 (60, [M À H2O ‡ H] ).
3-[2-(Carboxymethyl)-3,4-dimethoxyphenyl]prop-2-enoic Acid (31). To a soln. of 43 (90 mg, 0.32 mmol) in
MeOH (5 ml) was added aq. 2n KOH (2 ml). Stirring at r.t. for 2 h was followed by pouring into dil. aq. HCl
soln. and extraction with AcOEt. Evaporation yielded 31 (62 mg, 73%). Brownish oil. IR (KBr): 3500 2400
(br.), 2947m, 1687s, 1621m, 1591s, 1494s, 1465w, 1418m, 1272s, 1209w, 1079s, 1043m, 973m, 947m, 8 07m, 78 2w.
1H-NMR ((D6)acetone): 7.88 (d, J ˆ 15.7, 1 H); 7.51 (d, J ˆ 8.7, 1 H); 7.04 (d, J ˆ 8.7, 1 H); 6.98 (br., 2 H); 6.33
(d, J ˆ 15.7, 1 H); 3.92 (s, 3 H); 3.88 (s, 2 H); 3.81 (s, 3 H). 13C-NMR ((D6)acetone): 172.4 (s); 167.9 (s); 155.1
(s); 148.6 (s); 142.7 (d); 129.9 (s); 128.2 (s); 123.6 (d); 119.0 (d); 112.6 (d); 60.7 (q); 56.1 (q); 31.9 (t). CI-MS: 284
‡
‡
‡
‡
(100, [M ‡ NH4] ), 266 (11, [M À H2O ‡ NH4] ), 249 (19, [M À H2O ‡ H] ), 240 (84, [M À CO2 ‡ NH4] ), 223
‡
‡
(48, [M À CO2 ‡ H] ), 205 (13, [M À H2O À CO2 ‡ H] ).
Methyl 2-[6-(Dimethoxymethyl)-2,3-dimethoxyphenyl]-3-(3,4-dimethoxyphenyl)-3-hydroxypropanoate
(44). As described for 13, with 36 (0.82 g, 2.88 mmol) and veratrumaldehyde (0.50 g, 3.0 mmol) (9). CC
(SiO2, hexane/AcOEt 1:1) yielded 0.78g (60%) of 44. IR: 3500 (br.), 3020w, 2980m, 2940s, 2900m, 2840m,
1720s, 1600m, 1510m, 1490m, 1450s, 1460s, 1420w, 1370w, 1260s, 1150w, 1135m, 1110m, 1085s, 1040s, 990m, 930w,
900w, 8 60w, 8 30w. 1H-NMR (CHCl3): 7.09 (d, J ˆ 8.5, 1 H); 7.00 6.87 (m, 4 H); 5.74 (s, 1 H); 5.32 (d, J ˆ 4.1,
1 H); 4.06 (d, J ˆ 4.1, 1 H); 3.91 (s, 3 H); 3.90 (s, 3 H); 3.87 (s, 3 H); 3.76 (s, 3 H); 3.51 (s, 3 H); 3.47 (s, 3 H); 3.36
(s, 3 H); 1.40 (br. s, 1 H). 13C-NMR (CHCl3): 171.0 (s); 152.0 (s); 148.7 (s); 148.4 (s); 145.7 (s); 131.5 (s); 126.8
(s); 126.6 (s); 123.0 (d); 118.2 (d); 112.3 (d); 110.7 (d); 109.0 (d); 98.3 (d); 69.3 (d); 60.0 (q); 55.83 (q); 55.79
‡
(2q); 55.76 (q); 55.5 (q); 51.5 (q); 45.6 (d). ESI-MS: 473 ([M ‡ Na] ).
Methyl trans-2-(3,4-Dihydroxyphenyl)-4-formyl-2,3-dihydro-7-methoxybenzofuran-3-carboxylate (45) and
Methyl (2E)-3-(3,4-Dihydroxyphenyl)-2-(6-formyl-2-hydroxy-3-methoxyphenyl)prop-2-enoate (32). As descri-
bed for 15, with 44 (0.10 g, 0.22 mmol) and BBr3 (0.556 g, 0.21 ml, 2.20 mmol). CC (SiO2, CH2Cl2/MeOH 19 :1)
yielded 32 mg (42%) of 45 and 12 mg (15%) of 32.
Data for 45: IR: 3700 2900 (br.), 3020w, 2950w, 2840w, 1735s, 1685s, 1615s, 1580s, 1510w, 1450s, 1435s,
1400w, 1285s, 1165m, 1095s, 1015w. 1H-NMR (CHCl3): 9.81 (s, 1 H); 7.39 (d, J ˆ 8.3, 1 H); 6.96 (d, J ˆ 8.3, 1 H);
6.88 (s, 1 H); 6.80 (s, 1 H); 6.79 (s, 1 H); 5.95 (br. s, 2 H); 5.79 (d, J ˆ 6.5, 1 H); 4.67 (d, J ˆ 6.5, 1 H); 3.97
(s, 3 H); 3.76 (s, 3 H). 13C-NMR (CHCl3): 191.0 (d); 172.2 (s); 149.7 (2s); 144.2 (s); 144.0 (s); 132.5 (s); 128.7 (d);
126.5 (s); 124.4 (s); 118.3 (d); 115.4 (d); 112.6 (d); 111.8( d); 88.4 (d); 56.7 (d); 56.2 (q); 52.8( q). CI-MS: 345
‡
([M ‡ H] ).
Data for 32: IR: 3540m, 3500 3000 (br.), 2940w, 2840w, 1685s, 1600s, 1505w, 1435m, 1375m, 1335w, 1280s,
1110m, 1090m, 1030w, 98 0w, 940w, 8 60w. 1H-NMR ((D6)acetone): 9.82 (s, 1 H); 8.38 (s, 1 H); 7.95 (s, 1 H); 7.92
(s, 1 H); 7.88 (s, 1 H); 7.52 (d, J ˆ 8.5, 1 H); 7.18 (d, J ˆ 8.5, 1 H); 6.66 (d, J ˆ 8.2, 1 H); 6.59 6.57 (m, 2 H); 3.98
(s, 3 H); 3.67 (s, 3 H). 13C-NMR ((D6)acetone): 190.9 (d); 168.3 (s); 153.3 (s); 148.0 (s); 145.8( s); 145.4 (s);
143.0 (d); 128.9 (s); 127.8( s); 126.7 (s); 124.6 (d); 123.0 (s); 122.5 (d); 117.7 (d); 116.0 (d); 111.4 (d); 56.6 (q);
52.3 (q).
Methyl trans-4-(2-Carboxyethenyl)-2-(3,4-dihydroxyphenyl)-2,3-dihydro-7-methoxybenzofuran-3-carboxy-
late (46). As described for 5, with 45 (30 mg, 0.087 mmol) and malonic acid (45 mg, 0.44 mmol). CC (SiO2,
CH2Cl2/MeOH 10 :1) gave 12 mg (35%) of 46. IR: 3600 2400 (br.), 2940w, 2840w, 1725s, 1610s, 1500m, 1435m,
1380m, 1280s, 1120w, 1080m, 1010w, 98 0w. 1H-NMR ((D4)MeOH): 7.68( d,J ˆ 15.9, 1 H); 7.27 (d, J ˆ 8.6, 1 H);
6.99 (d, J ˆ 8.6, 1 H); 6.76 6.70 (m, 2 H); 6.29 (d, J ˆ 15.9, 1 H); 5.86 (d, J ˆ 5.3, 1 H); 3.91 (s, 3 H); 3.77
(s, 3 H). 13C-NMR ((D4)MeOH): 173.7 (s); 170.6 (s); 150.0 (s); 147.7 (s); 147.0 (s); 146.8( s); 142.7 (d); 133.3 (s);
8
)
One signal of a quaternary C-atom is overlapped by the solvent signal.

358
Helvetica Chimica Acta Vol. 86 (2003)
126.7 (s); 126.0 (s); 121.6 (d); 119.0 (d); 118.4 (d); 116.5 (d); 114.8( d); 113.5 (d); 88.9 (d); 57.2 (d); 56.8( q); 53.3
(q). ESI-MS: 385 (100, [M À H]À), 353 (22, [M À MeOH À H]À)9).
X-Ray Crystal-Structure Determination of Compound 1610).
The data collection and refinement
parameters are summarized in the Table, and a view of the molecule is shown in Fig. 1. All measurements were
made on Nonius-KappaCCD diffractometer [19], with graphite-monochromated MoKa radiation
a
(l 0.71073 ä) and an Oxford-Cryosystems Cryostream-700 cooler. Data reduction was performed with HKL
Denzo and Scalepack [20]. The intensities were corrected for Lorentz and polarization effects but not for
absorption. The structure was solved by direct methods with SIR92 [21], which revealed the positions of all non-
H-atoms. The crystal lattice contains CHCl3 molecules that lie close to and are, thus, necessarily disordered
about centres of inversion. Formally, the site-occupation factors for the atoms of the CHCl3 molecule should,
therefore, be 0.5, but the best refinement results were obtained when the site-occupation factors were allowed to
refine and then were held fixed at 0.444. This suggests that some of the CHCl3 has diffused out of the crystal
leaving some sites unoccupied. However, the parameters in the Table were calculated assuming a 1:2 ratio.
The non-H-atoms were refined anisotropically. The hydroxy H-atoms were placed in the positions indicated
by a difference electron density map and their positions were allowed to refine together with individual
isotropic displacement parameters. All remaining H-atoms were fixed in geometrically calculated positions
Table. Crystallographic Data for Compound 16
Crystallized from
CDCl3
Empirical formula
Formula weight [g molÀ1
Crystal color, habit
Crystal dimensions [mm]
Temperature [K]
C17H14O6 ¥ 0.5(CDCl3)
373.98
colorless, plate
0.08 Â 0.25 Â 0.25
160 (1)
]
Crystal system
Space group
orthorhombic
Pbca
Z
8
Reflections for cell determination
5263
2q range for cell determination [8]
4 60
Unit cell parameters a [ä]
16.1842 (2)
7.5777 (1)
26.1527 (4)
3207.34 (8)
1.549
0.354
f and w
60
b [ä]
c [ä]
V [ä3]
Dx [g cmÀ3
]
m(MoKa) [mmÀ1
Scan type
]
2q(max) [8]
Total reflections measured
Symmetry-independent reflections
Reflections used (I > 2s(I))
Parameters refined
Final R
53748
4692
2867
253
0.0461
wR
Weights
Goodness-of-fit
Secondary extinction coefficient
Final lmax/s
d1 (max; min) [e äÀ3
0.0465
[s2(Fo) ‡ (0.015Fo)2]À1
1.668
2 (1) ¥ 10À7
0.0004
0.25; À0.21
]
Measurement in the negative mode. The pseudomolecular ion is expected as [M À 1]À.
9
)
)
10
Crystallographic data (excluding structure factors) for the structure of 16 have been deposited with the
Cambridge Crystallographic Data Centre as supplementary publication No. CCDC-187704. Copies of the
data can be obtained, free of charge, on application to the CCDC, 12 Union Road, Cambridge CB21EZ,
UK (fax: ‡44(1223)336033; e-mail: deposit@ccdc.cam.ac.uk).

Helvetica Chimica Acta Vol. 86 (2003)
359
(d(CÀH) ˆ 0.95 ä), and each was assigned a fixed isotropic displacement parameter with a value equal to
1.2Ueq of its parent C-atom. Refinement of the structure was carried out on F by full-matrix least-squares
procedures which minimized the function Sw(j Fo jÀj Fc j )2. A correction for secondary extinction was applied.
Two reflections, whose intensities were considered to be extreme outliers, were omitted from the final
refinement. Neutral-atom scattering factors for non-H-atoms were taken from Maslen, Fox and O×Keefe [22],
and the scattering factors for H-atoms were taken from [23]. Anomalous dispersion effects were included in Fc
[24]; the values for f ' and f '' were those of [25]. The values of the mass attenuation coefficients are those of [26].
All calculations were performed with the teXsan crystallographic software package [27].
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Received July 2, 2002