Palladium(0)-catalyzed allylation of 2,2′-dihydroxybiphenyl by 1-ethenylcyclopropyl sulfonates: Preparation of 2,2′-bis(cyclopropylideneethoxy) biphenyls

Article abstract of DOI:10.1055/s-2002-34950

Dipotassium salts of 2,2′-dihydroxybiphenyl derivatives underwent palladium(0) catalyzed regioselective allylation by sulfonic esters (mesylates, tosylates) of 1-ethenylcyclopropanol to produce, in good yields, 2,2′-bis(cyclopropylideneethoxy)biphenyls, which are of biological interest. Whilst the tetrapotassium salt of 2,2′,6,6′-tetrahydroxybiphenyl, formed the triadduct 2,2′-tris(cyclopropylideneethoxy)hydroxybiphenyl as its main product. An unexpected palladium-induced rearrangement of the monoadducts 2-(2-cyclopropylideneethoxy)-2′-hydroxybiphenyl derivatives into the 2-[2-(1-ethenylcyclopropyloxy)]-2′-hydroxybiphenyl derivatives occurred; while the minor diastereomer of the monoadduct 2-[(2-cyclopropylidene-1-trimethylsilyl)ethoxy]-6,6-dimethoxy-2′- hydroxybiphenyl upon standing in CDCl₃, underwent Claisen rearrangement into the 2,2′-dihydroxy-6,6′-dimethoxy-3-(2-trimethylsilylethenyl) cyclopropylbiphenyl.

Full text of DOI:10.1055/s-2002-34950

PAPER
2271
Palladium(0)-Catalyzed Allylation of 2,2 -Dihydroxybiphenyl by 1-Ethenyl-
cyclopropyl Sulfonates: Preparation of 2,2 -Bis(cyclopropylideneethoxy)
biphenyls
P
reparation of 2,2
i
-Bis(cy
o
clopropylide
v
neethoxy)bi
a
a
Istituto di Chimica Biomolecolare, Sez: Sassari, CNR, Traversa La Crucca 3, reg. Baldinca, Li Punti, 07040 Sassari, Italy
b
Laboratoire des Carbocycles, UMR 8615, Institut de Chimie Moléculaire d’Orsay, Bât. 420, Université de Paris-Sud, 91405 Orsay,
France
Fax +33(1)69156278; E-mail: jasalaun@icmo.u-psud.fr
c
Dipartimento di Scienze Chimiche, Cittadella Universitaria Monserrato, 9042 Monserrato, Italy
Received 22 June 2002; revised 10 July 2002
2-biphenylcyclopropanecarboxylic acids 2 (R = H, Cl)
were recognized for their activity in alleviating inflamma-
tion, pain, hypoglycemia and ketosis;8a while ovicidal ac-
tivity against spider mites was found for the 2-biphenyl
Abstract: Dipotassium salts of 2,2 -dihydroxybiphenyl derivatives
underwent palladium(0) catalyzed regioselective allylation by sul-
fonic esters (mesylates, tosylates) of 1-ethenylcyclopropanol to pro-
duce, in good yields, 2,2 -bis(cyclopropylideneethoxy)biphenyls,
which are of biological interest. Whilst the tetrapotassium salt of cyclopropanecarboxylate 3.8b The vinylogous hydroxam-
2,2 ,6,6 -tetrahydroxybiphenyl, formed the triadduct 2,2 -tris(cyclo-
ic acid 4, examined for its ability to inhibit various en-
propylideneethoxy)hydroxybiphenyl as its main product. An unex-
zymes in the arachidonic acid cascade, was proved to be
pected palladium-induced rearrangement of the monoadducts 2-(2-
an active inhibitor of 5-lipoxygenase (rat basophilic leu-
cyclopropylideneethoxy)-2 -hydroxybiphenyl derivatives into the
kemia cell line);9 and the oxime ether 5, tested for its ac-
2-[2-(1-ethenylcyclopropyloxy)]-2 -hydroxybiphenyl derivatives
tivity at α- and β-adrenergic receptors, exhibited high
efficiency in the inhibition of isoprenaline-induced tachy-
cardia in anesthetized rats. (Figure 1).10
occurred; while the minor diastereomer of the monoadduct 2-
[(2-cyclopropylidene-1-trimethylsilyl)ethoxy]-6,6-dimethoxy-2 -
hydroxybiphenyl upon standing in CDCl3, underwent Claisen re-
arrangement into the 2,2 -dihydroxy-6,6 -dimethoxy-3-(2-tri-
methylsilylethenyl)cyclopropylbiphenyl.
COOH
Key words: palladium(0), 1-ethenylcyclopropyl sulfonates, biphe-
OH
nyls, allylation, rearrangements
CH3
O
O
The growing number of isolated naturally occurring bio-
active biphenyls1 led us to consider this moiety as a basic
and valued framework for the synthesis of new
pharmacologically2 and agrochemically3 active com-
pounds. Additionally, the restricted rotation of the biphe-
nyl backbone provides attractive building blocks, for
example, to produce peptides with a frozen conformation
entailing enhanced resistance to enzymatic degradation.4
Also worthy of note are cyclopropane containing com-
pounds, these are of great general interest to synthetic or-
ganic chemists, especially bioorganic chemists, because
they provide building blocks of unprecedented synthetic
potential,5 due to their broad spectrum of biological prop-
erties.6 This led to the idea of preparing biphenyls linked
to three-membered rings with the aim of developing new
structures and prospective bioassays.
H3C
OH
Laurebiphenyl-1
R
2
3
N
N
O
O
NH
HO
OH
In fact, a few rare examples of natural cyclopropane con-
taining biphenyls have been reported, for instance, a
dimeric sesquiterpene of the cyclolaurane type, laurebi-
phenyl-1 was isolated from the red alga Laurencia nidifi-
ca.7 Furthermore the bioactivity of several biphenyl-
cyclopropane derivatives has been noted. Thus, the basic
5
4
Figure 1
In pursuit of the synthetic applications of the -1,1-ethyl-
eneallylmetal complexes,11 we report herein an efficient
and selective method12 to prepare 2,2 -bis(2-cyclopropyl-
ideneethoxy)biphenyls. In fact, alkylidenecyclopropanes
form a peculiar class of strained olefinic compounds with
Synthesis 2002, No. 15, Print: 29 10 2002.
Art Id.1437-210X,E;2002,0,15,2271,2279,ftx,en;Z09402SS.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881

2272
G. Delogu et al.
PAPER
OR
Nub
Nua
LnPd(0)
or
Nua
or Nub
(+)
Pd
L
L
6a R=H
9
8
7
b
c
Ms
Ts
Scheme 1
remarkable synthetic potential,13 and specific bioactivi- upon treatment of 2,2 -dihydroxybiphenyl with equiv of
ties.6
K2CO3) with mesylate 6b (2 equiv), gave 2-(2-cyclopro-
pylideneethoxy)-2 -hydroxybiphenyl (12) as the major
product (79%), as well as the diadduct 11 (15%) and the
unexpected 2-(1-ethenylcyclopropyloxy)-2'-hydroxybi-
phenyl [(14; 4%) Table 1, entry 5].
Allylation of 2,2 -dihydroxybiphenyl: the sulfonic es-
ters (mesylate, tosylate) of the 1-ethenylcyclopropanol
6a (R = H), (readily available from the cyclopropanone
hemiacetal,14 1-hydroxycyclopropanecarboxylic acid,15
or recently from titanium(IV)-mediated cyclopropanation A sample of the monoadduct-I 12 remained unaltered
of β-halo esters,16) formed the -1,1-ethyleneallylpalladi- upon treatment with of K2CO3 (1 equiv) in DMF (60 °C
um complex 711 upon treatment with palladium(0). Then, for 7 d), proving that the rearrangement 12 14, was not
nucleophilic substitution of 7 by soft nucleophiles Nua– simply base-induced. On the other hand, reaction of the
(stabilized anions), provided the alkylidenecyclopropanes monoadduct-I 12 with palladium(0) [from 5% Pd(dba)2
–
8, while hard nucleophiles Nub (e.g., non stabilized orga- and 12% PPh3] in DMF at (r.t. for 16 h) gave the isomeric
nometallics), gave the 1-substituted vinylcyclopropanes monoadduct-II 14 in good yield (81%). Seemingly coor-
9, regioselectively (Scheme 1).11
dination of the double bond of the alkylidenecyclopro-
pane 12 with Pd(0) led to the formation of complex 15 and
then to the -1,1-ethyleneallylpalladium complex (16),
probably favoured by a H-bond between the oxygen and
the hydroxyl group. Therefore, the 2 -hydroxy-2-oxybi-
phenyl moiety must be regarded as a leaving group and a
nucleophile simultaneously. However, the palladium(0)
catalyzed reaction of the potassium salt of 12 (formed by
reaction with 1 equiv of K2CO3 in DMF at 60 °C for 1 h)
with the mesylate 6b, in DMF (r.t. for, 12 h, then 60 °C for
30 h) did not lead to the monoadduct-II 14, but to the di-
adduct 11 in poor yield (9%). This is probably because in
the presence of mesylate 6b palladium(0) forms complex
7 more readily than the complexes 15 and 16 (Scheme 2),
and therefore could not induce the rearrangement 12 14,
(Scheme 2).
Likewise reaction of the dipotassium salt 10 (formed upon
treatment of commercially available 2,2 -dihydroxybi-
phenyl with 3 equiv of K2CO3 in anhyd DMF at 60 °C for
2 h) with mesylate 6b (2.5 equiv, R = OMs) in the pres-
ence of palladium(0) {from palladium dibenzylideneace-
tone [Pd(dba)2] and 2PPh3}, in DMF (r.t. for 3 h) gave
2,2 -bis(2-cyclopropylideneethoxy)biphenyl [11; 45%],
and the monoadduct-I 12 [(16%) Table 1, entry 1]. Under
the same conditions, but using a greater amount of the me-
sylate 6b (4 equiv), improved the yield of 11 [(79%)
Table 1, entry 2)]. A longer reaction time (15 h) improved
the yield of 11 further [(90%) Table 1, entry 3]. However,
palladium(0) catalyzed nucleophilic substitution of the to-
sylate 6c (R = Ts) by the dipotassium salt 10 (4 equiv, 15
h) led to the diadduct 11 (70%), revealing the leaving
group effect of the sulfonate (Table 1, entry 4).
It must be also emphasized for comparison that the diad-
duct 11 did not undergo any rearrangement upon treat-
ment with Pd(0) in DMF at (r.t. for 16 h).
On the other hand, Pd(0)-catalyzed reaction under the
same conditions of the monopotassium salt 13 (formed
PdL2
14
K2CO3
L2Pd
LnPd(0)
O
14
O
12
H
1) K2CO3
OH
(81%)
O
2) 7
11
(9%)
16
15
Scheme 2
Synthesis 2002, No. 15, 2271–2279 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Preparation of 2,2 -Bis(cyclopropylideneethoxy)biphenyls
2273
Table 1 Palladium(0)-Catalyzed Nucleophilic Substitution of 1-Ethenylcyclopropyl Sulfonates by 2,2 -Dihydroxybiphenyls
Entry Nucleophile
Sulfonic
T °C
Diadduct
Monoadduct-I (%)
Monoadduct-II (%)
ester (equiv) (reaction
time)
O
O
OK
OK
O
OH
1
2
3
4
10
10
10
10
6b (2.5)
6b (4)
r.t. (3 h) 11 (45)
r.t. (3 h) 11 (79)
r.t. (15 h) 11 (90)
r.t. (15 h) 11 (70)
12 (16)
12 (16)
12 (10)
–
–
–
6b (2.2)
6c (4)
OK
OH
O
OH
5
13
6b (2)
r.t. (3 h) 11 (15)
12 (79)
14 [4; 81 from 12 and
Pd(0)]
CH3O
CH3O
OK
OK
CH3O
CH3O
O
O
CH3O
CH3O
O
OH
6
7
17
17
6b (4)
r.t. (12 h) 18 (60)
r.t. (24 h) 18 (70)
19 (0)
–
–
6c (2.2)
19 (30)
OK
OK
O
O
8
20
6b (4)
r.t. (12 h) 21 (84)
–
–
OCH3
OCH3
OCH3
OCH3
O
O
O
O
OK
OK
OH
OH
OCH3
OCH3
OCH3
OCH3
9
10
11
22
22
22
6b (2.5)
6b (4)
6c (4)
r.t. (14 h) 23 (50)
r.t. (64 h) 23 (50)
r.t. (20 h) 23 (35)
24 (3)
25 (2)
24 (40)
24 (63)
25 (10)
25 (2)
KO
KO
OK
OK
O
O
O
O
O
O
O
OH
26
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2274
G. Delogu et al.
PAPER
Table 1 Palladium(0)-Catalyzed Nucleophilic Substitution of 1-Ethenylcyclopropyl Sulfonates by 2,2 -Dihydroxybiphenyls (continued)
Entry Nucleophile
Sulfonic
T °C
Diadduct
Monoadduct-I (%)
Monoadduct-II (%)
ester (equiv) (reaction
time)
12
26
6b (8)
r.t. (12 h) 27a (15)
28b (60)
O
OH
OH
HO
HO
O
HO
OH
13
26
6b (4)
r.t. (3 d)
29 (60)
30 (40)
OMe
OMe
Br
Br
OK
OK
Br
Br
O
O
OMe
OMe
14
31
6c (2.3)
r.t. (3 h) 32 (75)
OTs
SiMe3
SiMe3
SiMe3
MeO
MeO
O
MeO
MeO
OH
OH
OH
15
17
6d (2.4)
r.t. (3 h)
33 (25; de: 20%)
34c (90%)
a Tetraadduct .
b Triadduct.
c From CDCl3 catalyzed Claisen rearrangement of 33.
Allylation of 2,2 -dihydroxy-6,6 -dimethoxybiphenyl: the damage to cells, in particular to skin, and provoke food
reaction of the dipotassium salt 17 (formed upon treat- deterioration.21 Its dipotassium salt 22 (obtained upon
ment of 2,2 -dihydroxy-6,6 -dimethoxybiphenyl,17 with 3 treatment of dehydrodieugenol,18 with 3 equiv of K2CO3
equiv of K2CO3 in anhyd DMF at 60 °C for 1 h), with me- in anhyd DMF at 60 °C for 1 h), when reacted with mesy-
sylate 6b (4 equiv) in the presence of palladium(0) in late 6b (2.5 equiv) in the presence of palladium(0) (r.t. for
DMF (r.t. for 12 h), produced the 2,2 -bis(2-cyclopropyl- 14 h), underwent allylation to provide the 2,2 -bis(2-cy-
ideneethoxy)-6,6 -dimethoxybiphenyl 18 [(60%) Table 1, clopropylideneethoxy)-3,3 -dimethoxy-5,5 -di(2-propen-
entry 6]. The dipotassium salt 17 when subjected to simi- yl)biphenyl (23; 50%), as well as the monoadducts 24 and
lar conditions, but using less tosylate 6c and with a longer 25 [(3% and 2%, respectively) Table 1, entry 9].
reaction time (2.2 equiv at r.t. for 24 h), underwent mono-
and dialkylation to produce the 2-(2-cyclopropylide-
Palladium(0)-catalyzed reaction of 22 with mesylate 6b (4
equiv) for a longer reaction time (64 h) increased the
neethoxy)-6,6 -dimethoxy-2 -hydroxybiphenyls 19 and
yields of 24 and 25 [(40% and 10%, respectively) Table 1,
18 [(30% and 70%, respectively) Table 1, entry 7].
entry 10]. Otherwise use of tosylate 6c (4 equiv for 20 h)
Allylation of 1,1 -bi-2-naphthol: palladium(0)-catalyzed gave the monoadduct-I 24 as major product [(63%)
reaction of the dipotassium salt 20 (prepared upon treat- Table 1, entry 11].
ment of commercially available racemic 1,1 -bi-2-naph-
Formation of the rearranged monoadduct-II 25 was ob-
thol with 3 equiv of K2CO3 in anhyd DMF at 60 °C for 1
served after a longer reaction time (64 h at r.t.); whilst
h) with mesylate 6b (4 equiv) in DMF (r.t. for 12 h) led to
treatment of monoadduct-I 24 with palladium(0) [from
the 2,2 -bis(2-cyclopropylideneethoxy)-1,1 -binaphtha-
5% Pd(dba)2 and 12% PPh3] in DMF (r.t. for 16 h) gener-
lene (21) in good yield (84%), without noticeable forma-
ates a rearrangement to form the monoadduct-II 25 in
tion of a monoadduct (Table 1, entry 8).
good yield (60%).
Allylation of 5,5 -bis(2-propenyl)-2,2 -dihydroxy-3,3 -
Allylation of 2,2 ,6,6 -tetrahydroxybiphenyl: the tetrapo-
dimethoxybiphenyl (dehydrodieugenol): this natural
tassium salt 26 (prepared by treatment of 2,2 ,6,6 -tetrahy-
product can be isolated from various plants including the
droxybiphenyl,22 with K2CO3 (5 equiv) in anhyd DMF at
wood of an arboreous Lauracea species from the Andes
60 °C for 1 h) similarly underwent palladium(0)-catalyzed
allylation upon treatment with an excess (8 equiv) of me-
sylate 6b in DMF (r.t. for 12 h) to produce the triadduct 28
(Nectandra polita).18 Dehydrodieugenol is an efficient
hydroxyl radical scavenger,19 able to inhibit UV-induced
mutagenesis20 and lipid peroxidation, which entail fatal
Synthesis 2002, No. 15, 2271–2279 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Preparation of 2,2 -Bis(cyclopropylideneethoxy)biphenyls
2275
1-Ethenyl-1-tosyloxycyclopropane (6c)
as the principal product (60%), as well as 2,2 ,6,6 -tet-
rakis(2-cyclopropylideneethoxy)biphenyl 27 [(15%)
Table 1, entry 12]. Curiously, in this case, the formation
of mono- or diadducts was not observed in the crude reac-
tion mixture. However, palladium(0) catalyzed reaction
of 26 with less mesylate 6b (4.4 equiv) was slower but af-
ter stirring the reaction mixture for a long period of time
(r.t. for 3 d) produced the monoadduct-I 29 (60%), and the
isomeric monoadduct-II 30 [(40%) Table 1, entry 13].
This probably arises from a palladium(0)-catalyzed rear-
rangement analogous to 12 14 (Scheme 2).
Compound 6c was prepared from titanium(IV)-mediated cyclopro-
panation of ethyl –chloropropionate and one-pot tosylation, ac-
cording to known procedures.16
1-Tosyloxy-1-1(2-trimethylsilylethenyl)cyclopropane (6d)
Compound 6d was prepared from cyclopropanone hemiacetal, fol-
lowed by tosylation according to known procedures.11d
Palladium(0)-Catalyzed Substitution of 1-Ethenyl-1-mesyloxy-
cyclopropane (6b) by the Dipotassium Salt of 2,2 -dihydroxybi-
phenyl (10); Typical Procedure
A solution of Pd(dba)2 (32mg, 0.055 mmol) and of PPh3 (35 mg,
0.13 mmol) was degassed under vacuum for 1 h and stirred in a N2
atmosphere, to this was added a solution of mesylate 6b (178 mg,
1.1 mmol) in anhyd DMF (20 mL). The mixture was stirred at r.t.
for 15 min, then a solution of the dipotassium salt 10 [0.5 mmol;
generated from the reaction of 2,2 -dihydroxybiphenyl (93 mg, 0.5
mmol) with K2CO3 (207 mg, 1.5 mmol) in anhyd DMF (5 mL) for
2 h at 60 °C] was added. Stirring was continued at r.t. for 15 h; then,
Et2O (20 mL) and sat. NH4Cl (20 mL) were added. The organic
phase was extracted with Et2O (2 20 mL ) and dried over Na2SO4.
Removal of the solvent in vacuo and flash chromatography (C5H12–
Et2O, 9:1) of the residue gave 2,2 -bis-(2-cyclopropylide-
neethoxy)biphenyl (11; 143 mg 90%), and 2 -(2-cyclopropylidene
ethoxy)-2 -hydroxybiphenyl (12; 13 mg 10%).
Allylation of 6,6-dibromo-2,2 -dihydroxy-3,3 -dimethox-
ybiphenyl: the dipotassium salt 31 (formed upon treat-
ment of 6,6-dibromo-2,2 -dihydroxy-3,3 -dimethoxy-
biphenyl,23 with K2CO3 (4 equiv) in anhyd DMF at 60 °C
for 1 h) readily underwent reaction with the tosylate 6c
(2.3 equiv) in the presence of 5% of palladium(0) (at r.t.
for 3 h). This produced the 2,2 -bis(2-cyclopropylide-
neethoxy)-6,6-dibromo-3,3 -dimethoxy-biphenyl (32) in
good yield [(75%) Table 1, entry 14].
Nucleophilic substitution of 1-tosyloxy-1-1(2-trimethyl-
silylethenyl)cyclopropane by 2,2 -dihydroxy-6,6 -di-
methoxy-biphenyl, Claisen rearrangement: reaction of the
dipotassium salt 17, with the 1-(2-trimethylsilylethe-
nyl)cyclopropyl tosylate 6d in the presence of 5% of pal-
ladium(0) in DMF (r.t. for 3 h) led to a 60:40
diastereomeric mixture of 2-[(2-cyclopropylidene-1-
trimethylsilyl)ethoxy]-6,6-dimethoxy-2 -hydroxybiphen-
yl (33; 25%). This resulted from hindered rotation along
the main biphenyl axis. On standing in CDCl3 for several
weeks only the minor diastereomer of 33 underwent
Claisen rearrangement24 to provide the 2,2 -dihydroxy-
6,6 -dimethoxy-3-[1-(2-trimethylsilylethenyl)cycloprop-
yl)]biphenyl [(34; 90%) Table 1, entry 15).
2,2 -Bis-(2-cyclopropylideneethoxy)biphenyl (11)
Colorless oil.
IR (CDCl3): 3100–2800, 1593, 1480, 1261 cm–1.
1H NMR (CDCl3): = 1.03 (s, 8 H), 4.65 (d, 4 H, J = 5.8 Hz), 5.8
(m, 2 H), 6.9 (t, 4 H, J = 6.8 Hz), 7.3 (m, 4 H).
13C NMR (CDCl3): = 1.8, 1.9, 68.6, 112.8, 114.3, 120.2, 125.9,
128.1, 128.5, 131.5, 156.2.
MS (EI) m/z (%) = 318 (50) [M+], 289 (100), 247 (57), 233 (79), 219
(57), 181 (62), 165 (65).
HRMS: m/z calcd for C22H22O2: 318.1619; found: 318.1616.
2 -(2-Cyclopropylideneethoxy)-2 -hydroxybiphenyl (12)
Colorless oil.
IR (CDCl3): 3800–3200, 3100, 2800, 1593, 1480, 1261 cm–1.
1H NMR (CDCl3): = 1.2 (s, 4 H), 4.8 (d, 2 H, J = 6.3 Hz), 5.9–6.1
A sample of the dihydroeugenol derivative 23, is currently
under investigation in order to test its eventual bioactivity
on plants.
(m, 1 H), 6.9–7.2 (m, 4 H), 7.3–7.5 (m, 4 H).
13C NMR (CDCl3): = 1.01, 1.9, 69.6, 112.6, 113.6, 117.7, 121,
122.4, 126.7, 128, 128.8, 129, 129.1, 131.3, 132.6, 153.9, 154.5.
MS (EI) m/z (%) = 252 (100) [M+], 237 (56), 223 (38), 165 (17), 181
(15), 115 (10).
1H NMR spectra were recorded on Brücker AM 250 (250 MHz),
AC 250 (250 MHz) and AC 200 (200 MHz) spectrometers; = 0 for
TMS, 7.27 for CHCl3. 13C NMR spectra were also recorded on
Brüker AM 250, AC 250 (63 MHz), AC 200 (50 MHz): = 77 for
CDCl3, the NMR data are reported in (ppm) from TMS. The
DEPT-135 pulse was used for the determination of signal types. IR
spectra were run on a FT-IR Perkin Elmer spectrophotometer. Mass
spectra were measured with a Nermag R-10 coupled with a OKI DP
125 gas chromatographer. Relative percentages are shown in brack-
ets; high resolution mass spectra were recorded with a Finningan
MAT 95S. Elemental analyses were performed with a Perkin-Elmer
240 C analyzer by the Service of Microanalyse, Institut de Chimie
des Substances Naturelles, Gif-sur-Yvette (France). Preparative
column chromatography was performed on SDS normal silica gel
(70–230 mesh), on SDS flash silica gel (35–70 mesh) or on Fluka
neutral alumina 507c (100–200 mesh). All reactions requiring anhy-
drous conditions were performed under argon.
HRMS: m/z calcd for C17H16O2: 252.1150; found: 252.1153.
Palladium(0)-Catalyzed Allylic Substitution of 1-Ethenyl-1-to-
syloxycyclopropane (6c) by the Dipotassium Salt 10 of 2,2 -Di-
hydroxybiphenyl
A mixture of tosylate 6c (952 mg, 4 mmol), Pd(dba)2 (120 mg, 0.2
mmol), and PPh3 (105 mg, 0.4 mmol) was stirred at r.t. in anhyd
DMF (20 mL) for 15 min. A solution of the dipotassium salt 10 (1
mmol; generated as above) was added and stirring continued at r.t.
for 15 h, then the reaction was heated at 60 °C for 4 d. After addition
of Et2O (20 mL) and sat. NH4Cl (20 mL), the organic phase was ex-
tracted with Et2O (2 20 mL) and dried over Na2SO4. Removal of
the solvent in vacuo and flash chromatography (C5H12–Et2O, 9:1) of
the residue gave 11 as a colorless oil (220 mg, 70%).
1-Ethenyl-1-mesyloxycyclopropane (6b)
Compound 6b was prepared from vinylation of cyclopropanone
hemiacetal, followed by mesylation according to known proce-
dures.11a,14
Synthesis 2002, No. 15, 2271–2279 ISSN 0039-7881 © Thieme Stuttgart · New York

2276
G. Delogu et al.
PAPER
Palladium(0)-Induced Rearrangement of 12
Method A
mmol; generated as above) was added and the reaction mixture
stirred at r.t. for 24 h. After addition of Et2O (20 mL) and sat.
NH4Cl (20 mL), the organic phase was extracted with Et2O (2 20
mL) and dried over Na2SO4. Removal of the solvent in vacuo and
flash chromatography (C5H12–Et2O, 1:1) of the residue gave the
pure products 18 and 19 (70% and 30% respectively).
Attempted base-induced rearrangement: A solution of 2-(2-cyclo-
propylideneethoxy)-2 -hydroxybiphenyl 12 (202 mg, 0.8 mmol)
and K2CO3 (110 mg, 0.8 mmol ) was stirred for 7 d in anhyd DMF
(5 mL) at 60 °C. After addition of Et2O (20 mL) and sat. NH4Cl (20
mL), the organic phase was extracted with Et2O (2 20 mL) and
dried on Na2SO4. Removal of the solvent in vacuo recovered the un-
reacted 12 (200 mg, 0.8 mmol).
2-(2-Cyclopropylideneethoxy)-6,6 -dimethoxy-2 -hydroxybi-
phenyl (19)
Colorless oil.
IR (CDCl3): 3800–3200, 3100–2800, 1593, 1480, 1261 cm–1.
Method B
Palladium(0)-induced rearrangement: A mixture of 12 (186 mg,
0.73 mmol), Pd(dba)2 (21.21 mg, 0.037 mmol) and PPh3 (23.2 mg,
0.088 mmol) was stirred overnight in anhyd DMF (15 mL) at r.t..
After addition of Et2O (20 mL) and of sat. NH4Cl (20 mL), the or-
ganic phase was extracted with Et2O (2 20 mL) and dried over
Na2SO4. Removal of the solvent in vacuo produced 2-(1-ethenylcy-
clopropyloxy)-2 -hydroxybiphenyl 14 (150 mg, 81%); the lack of
12 in the crude product proved that the conversion was complete.
1H NMR (CDCl3): = 1.03 (s, 4 H), 3.73 (s, 3 H), 3.76 (s, 3 H), 4.75
(d, 2 H, J = 4,4 17, 11 Hz), 5.11 (s, 1 H), 5.81–6.02 (m, 1 H), 6.52–
6.63 (m, 1 H), 6.63–6.82 (m, 3 H), 7.21–7.42 (m, 2 H).
13C NMR (CDCl3): = 1.86, 2.03, 55.86, 55.98, 68.94, 103.22,
104.3, 106.26, 108.57, 110.02, 110.05, 113.64, 126.66, 128.95,
129.83, 154.27, 157.66, 158.58, 159.22.
MS (EI) m/z (%) = 313 (21) [MH+], (M) 312 (100).
HRMS: m/z calcd for C19H20NaO4 (M + Na): 335.1259; found:
335.1259.
2-(1-Ethenylcyclopropyloxy)-2 -hydroxybiphenyl (14)
Colorless oil.
IR (CDCl3): 3600–3100, 3060–2900, 1594, 1483, 1440, 1266 cm–1.
Palladium(0)-Catalyzed Allylic Substitution of 1,1 -Bi-2-naph-
thol
1H NMR (CDCl3): = 1.09 (m, 2 H), 1.325 (m, 2 H), 5.13 (dd, 1 H,
J = 17, 11 Hz), 5.75 (dd, 1 H, J = 17, 11 Hz), 6.26 (s, 1 H), 6.95–
7.21 (m, 4 H), 7.26–7.42 (m, 4 H).
A mixture of mesylate 6b (648 mg, 4 mmol), Pd(dba)2 (28.75 mg,
0.05 mmol), and PPh3 (1.44 mg, 0.120 mmol) in anhyd DMF (20
mL) was stirred at r.t. for 15 min, then a solution of the dipotassium
salt 20 [1 mmol; generated from 1,1 -bi-2-naphthol (286 mg, 1
mmol) and K2CO3 (414 mg, 3 mmol ) in anhyd DMF (5 mL) heated
for 1 h at 60 °C] was added and stirring continued for 12 h at r.t.,
After addition of Et2O (20 mL) and sat. NH4Cl (20 mL), the organic
phase was extracted with Et2O (2 20 mL) and dried over Na2SO4.
Removal of the solvent in vacuo and flash chromatography of the
residue, (C5H12–Et2O, 9:1) gave the pure compound 21 (368 mg,
84%).
13C NMR (CDCl3):
= 15.88, 61.07, 113.12, 115.55, 117.23,
120.83, 122.02, 126.27, 126.92, 128.65, 129.06, 131.25, 132.36,
137.50, 153.38, 153.52.
MS (EI) m/z (%) = 252 (54) [M+], 234 (100), 186 (86), 179 (86), 131
(55), 129 (55), 103 (47).
HRMS: m/z calcd for C17H16O2: 252.1150; found: 252.1150.
Palladium(0)-Catalyzed Allylic Substitution of 2,2 -Dihydroxy-
6,6 -dimethoxybiphenyl
2,2 -Bis-(2-cyclopropylideneethoxy)-1,1 -binaphthalene (21)
Colorless oil.
IR (CDCl3): 3300–2700, 1591, 1507, 1261 cm–1.
1H NMR (CDCl3): = 0.81 (s, 4 H), 0.96 (s, 4 H), 4.65 (d, 4 H, J =
6.3 Hz), 5.68–5.8 (m, 2 H), 7.12–7.16 (d, 2 H), 7.28–7.24 (dd, 2 H,
J = 7.5, 0.9 Hz), 7.28–7.36 (dd, 2 H, J = 6.4, 1.4 Hz), 7.41–7.46 (d,
2 H, J = 9.0 Hz), 7.84 (d, 2 H, J = 8.3 Hz), 7.92 (d, 2 H, J = 8.8 Hz).
13C NMR (CDCl3): = 1.79, 1.95, 69.72, 144.30, 116.14, 120.69,
123.44, 125.53, 126.00 126.25, 127.75, 128.91, 129.26, 134.13,
154.20.
To a mixture of mesylate 6b (324 mg, 2 mmol), Pd(dba)2 (58 mg,
0.1 mmol) and PPh3 (53 mg, 0.2 mmol) in anhyd DMF (20 mL) was
added a solution of the dipotassium salt 17 [0.5 mmol; generated
from the reaction of 2,2 -dihydroxy-6,6 -dimethoxybiphenyl (17)
(123 mg, 0.5 mmol) with K2CO3 (207 mg, 1.5 mmol ) in anhyd
DMF (5 mL) for 1 h at 60 °C] This reaction mixture was stirred at
r.t. for 12 h. After addition of Et2O (20 mL) and sat. NH4Cl (20 mL),
the organic phase was extracted with Et2O (2 20 mL) and dried
over Na2SO4. Removal of the solvent in vacuo and flash chromatog-
raphy (C5H12–Et2O, 1:1) of the residue gave the pure product 18
(116 mg, 60%).
MS (EI) m/z (%) = 418 (54) [M+], 268 (100), 284 (72), 351 (68), 255
(62), 239 (53).
2,2 -Bis-(2-cyclopropylideneethoxy)-6,6 -dimethoxybiphenyl
(18)
Colorless oil.
HRMS: m/z calcd for C30H26O2: 418.1933; found: 418.1939.
IR (CDCl3): 3100–2800, 1593, 1480, 1261 cm–1.
Palladium(0)-Catalyzed Allylic Substitution of 5,5 -Bis(2-pro-
penyl)-2,2 -dihydroxy-3,3 -dimethoxybiphenyl (Dehydrodieu-
genol)
1H NMR (CDCl3): = 1.02 (s, 8 H), 3.74 (s, 6 H), 4.64 (d, 4 H, J =
5.3 Hz), 5.8–5.9 (m, 2 H), 6.64 – 6.68 (d, 2 H, J = 8.3 Hz), 6.66–
6.71 (d, 2 H, J = 5.3 Hz), 7.42–7.33 (t, 2 H, J = 8.3).
13C NMR (CDCl3): = 1.74, 1.87, 55.83, 68.89, 104.09, 105.96,
113.18, 114.46, 125.36, 128.21, 157.45, 158.33.
A mixture of mesylate 6b (586.5 mg, 3.62 mmol), Pd(dba)2, (41.68
mg, 0.072 mmol) and PPh3 (45.6 mg, 0.174 mmol) in anhyd DMF
(40 mL) was stirred for 14 h at r.t with the dipotassium salt 22 [1.45
mmol; generated from dehydrodieugenol,18 (473, mg 1.45 mmol)
and K2CO3 (301 mg, 2.18 mmol) in anhyd DMF (5 mL) for 1 h at
60 °C]. After addition of Et2O (20 mL) and sat. NH4Cl (20 mL), the
organic phase was extracted with Et2O (2 20 mL) and dried over
Na2SO4. Removal of the solvent in vacuo and flash chromatography
(C5H12–Et2O, 4:1) of the residue, gave the pure products 23 (332
mg, 50%), 24 and 25.
MS (EI) m/z (%) = 379 (27) [M+], 378 (100)
HRMS: m/z calcd for C24H26NaO2 (M + Na): 401.1728; found:
401.1729.
A mixture of tosylate 6c (547 mg, 2.4 mmol), Pd(dba)2 (17.25 mg,
0.03 mmol), and PPh3 (18.86 mg, 0.072 mmol) in anhyd DMF (20
mL) was stirred at r.t. for 15 min, then the potassium salt 17, (0.6
Synthesis 2002, No. 15, 2271–2279 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Preparation of 2,2 -Bis(cyclopropylideneethoxy)biphenyls
2277
2,2 -Bis(2-cyclopropylideneethoxy)-3,3 -dimethoxy-5,5 -di(2-
propenyl)biphenyl (23)
Colorless oil.
IR (CDCl3): 3000–2700, 1581, 1462, 1268 cm–1.
1H NMR (CDCl3): = 0.92 (m, 4 H), 1.02 (m, 4 H), 3.35 (d, 4 H,
J = 7.9 Hz), 3.92 (s, 6 H), 4.41 (d, 4 H, J = 7.9 Hz ), (5.10 m, 4 H),
5.81–5.92 (m, 2 H), 5.92–6.11 (m, 2 H), 6.72 (d, 2 H, J = 1.8 Hz),
6.77 (d, 2 H, J = 1.8 Hz).
mL) was stirred for for 12 h at r.t. with the tetrapotassium salt 26 [1
mmol; generated from 2,2 ,6,6 -tetrahydroxybiphenyl (26)22 (218
mg, 1 mmol) and K2CO3 (345 mg, 2.5 mmol) in anhyd DMF (5 mL)
for 1 h at 60 °C]. After addition of Et2O (20 mL) and sat. NH4Cl (20
mL), the organic phase was extracted with Et2O (2 20 mL) and
dried over Na2SO4. Removal of the solvent in vacuo and flash chro-
matography of the residue (C5H12–Et2O, 6:4), gave the pure prod-
ucts 27 (75 mg, 15%) and 28 (75 mg, 60%).
13C NMR (CDCl3): = 1.37, 2.10, 40.02, 55.81, 73.11, 111.63,
114.89, 115.62, 123.50, 126.31, 132.94, 134.68, 137.44, 144.01,
152.73.
MS (EI) m/z (%) = 458 (7) [M+], 391 (26), 350 (100), 321 (88), 281
(31), 240 (17), 214 (40), 165 (15), 40 (23).
2,2 ,6,6′-Tetra-(2-cyclopropylideneethoxy)biphenyl (27)
Colorless oil.
IR (CDCl3): 3100–2800, 1593, 1480, 1261 cm–1.
1H NMR (CDCl3): = 0.99 (s, 8 H), 4.55–4.65 (d, 8 H, J = 5.8 Hz),
5.85–5.95 (m, 4 H), 6.60–6.64 (d, 4 H, J = 8.3 Hz), 7.14–7.23 (t, 2
H, J = 8.3 Hz).
HRMS: m/z calcd for C30H34O4: 458.2461; found 458.2454.
13C NMR (CDCl3): = 1.70, 1.81, 68.78, 105.71, 114.46, 114.57,
125.16, 127.83, 157.57
MS (EI) m/z (%) = 483 (36) [M+], 482 (100).
2-(2-Cyclopropylideneethoxy)-3,3 -dimethoxy-5,5 -di(2-
propenyl)biphenyl-2 -hydroxybiphenyl (24)
As above a mixture of mesylate 6b (648 mg, 4 mmol), Pd(dba)2
(46.3 mg, 0.08 mmol), and PPh3 (49.8 mg, 0.19 mmol) was stirred
for 64 h at r.t.with the dipotassium salt 22 [1 mmol; generated as
above from dehydrodieugenol18 (326.2 mg, 1 mmol) and K2CO3
(207 mg, 1.5 mmol)]. After addition of Et2O (20 mL) and sat.
NH4Cl (20 mL), the organic phase was extracted with Et2O (2 20
mL) and dried over Na2SO4. Removal of the solvent in vacuo and
flash chromatography (C5H12–Et2O, 4:1) of the residue, gave the
pure products 24 (156 mg, 40%) and 25 (39 mg, 10%).
HRMS: m/z calcd for C32H34NaO4 (M + Na): 505.2355; found
505.2355.
2 -Hydroxy-2,6,6 -tris-(2-cyclopropylideneethoxy)biphenyl (28)
Colorless oil.
IR (CDCl3): 3800–3200, 3100–2800, 1561, 1480, 1259 cm–1.
1H NMR (CDCl3): = 1.01 (s, 12 H), 4.52–4.71 (m, 6 H), 5.81–5.92
(m, 3 H), 6.52–6.73 (m, 4 H), 7.15–7.31 (m, 2 H).
13C NMR (CDCl3): = 1.84, 1.90, 2.09, 65.85, 68.94, 104.89,
106.15, 108.67, 113.82, 114.50, 125.49, 126.50, 128.67, 128.82,
129.46, 157.62, 157.81.
MS (EI) m/z (%) = 416 (53) [M+], 349 (76), 91 (86), 77 (85), 67
(100).
Colorless oil.
IR (CDCl3): 3800–3200, 3100–2800, 1582, 1452, 1268 cm–1.
1H NMR (CDCl3): = 0.92 (m, 2 H), 1.02 (m, 2 H), 3.35 (d, 4 H,
J = 5.8 Hz), 3.8 (s, 3 H), 3.89 (s, 3 H), 4.87 (d, 2 H, J = 7.9 Hz), 5.11
(m, 4 H), 5.81–5.92 (m, 1 H), 5.92–6.09(m, 2 H), 6.65–6.81 (m, 4
H).
A mixture of mesylate 6b (712.8 mg, 4.4 mmol), Pd(dba)2 (126.5
mg, 0.22 mmol) and PPh3 (138.3 mg, 0.53 mmol) in anhyd DMF
(20 mL) was stirred for 15 min; then the potassium salt 26 (1 mmol;
generated as above) was added and the reaction mixture stirred at
r.t. for 3 d. After addition of Et2O (20 mL) and sat. NH4Cl (20 mL),
the organic phase was extracted with Et2O (2 20 mL) and dried
over Na2SO4. Removal of the solvent in vacuo and flash chromatog-
raphy of the residue (C5H12–Et2O, 1:1), gave the pure products 29
(170 mg, 60%) and 30 (114 mg, 40%).
13C NMR (CDCl3):
109.59, 111.61, 111.76, 114.98, 115.66, 123.41, 123.66, 126.156,
133.387, 133.855, 134.67, 134.85, 137.39, 137.48, 140.56, 152.76,
152.91.
MS (EI) m/z (%) = 392 (4) [M+], 350 (13), 321 (100), 280 (10), 281
(15), 280 (10), 268 (7), 214 (5), 55 (30).
=1.47, 2.13, 40.03, 55.65, 55.85, 73.14,
HRMS: m/z calcd for C25H28O4: 392.1990; found 392.1990.
3,3 -Dimethoxy-5,5 -di(2-propenyl)-2-(1-ethenylcyclopropy-
loxy)-2 -hydroxybiphenyl (25)
Colorless oil.
IR (CDCl3): 3600–3150, 3100–2850, 1583, 1453, 1267 cm–1.
1H NMR (CDCl3): = 0.93 (m, 2 H), 1.04 (m, 2 H), 3.32 (d, 4 H,
J = 6 Hz), 3.80 (s, 3 H), 3.87 (s, 3 H), 4.72 (dd, 1 H, J = 10.8, 1.5
Hz), 4.83 (dd, 1 H, J = 17.7, 1.5 Hz), 5.03–5.12 (m, 4 H), 5.30 (s, 1
H), 5.82–5.87 (m, 1 H), 5.88–6.03 (m, 2 H), 6.69 (m, 4 H).
2-(2-Cyclopropylideneethoxy)-2 ,6,6 -trihydroxybiphenyl (29)
Colorless oil.
1H NMR (CDCl3): = 1.11 (s, 4 H), 4.25 (m, 2 H), 5.95–6.08 (m, 1
H), 7.36–7.57 (m, 6 H).
13C NMR (CDCl3): = 1.84, 1.90, 2.09, 65.85, 68.94, 104.89,
106.15, 108.67, 113.82, 114.50, 125.49, 126.50, 128.67, 128.82,
129.46, 157.62, 157.81.
13C NMR (CDCl3): = 14.46, 19.42, 40.02, 55.83, 56.026, 73.29,
109.67, 111.62, 111.75, 114,98, 115.75, 123.41, 123.65, 128.79,
129.57, 129.70, 130.88, 132.47, 140.49, 152.73.
MS (EI) m/z (%) = 392 (4) [M+], 350 (13), 321 (100), 280 (10), 281
(15), 280 (10), 268 (7), 214 (5), 55 (30).
2-(1-Ethenylcyclopropyloxy)-2 ,6,6 -trihydroxybiphenyl (30)
Colorless oil.
1H NMR (CDCl3): = 0.83 (m, 2 H), 0.95 (m, 2 H), 4.98–5.08 (m),
5.60–5.75 (m, 1 H), 6.60–6.84 (m, 4 H), 7.19–7.33 (m, 2 H).
13C NMR (CDCl3): = 15.96, 60.93, 108.23, 108.32, 112.99,
130.89, 131.20, 137.76, 154.68.
HRMS: m/z calcd for C25H28O4: 392.1990; found 392.1990.
MS (EI) m/z (%) = 284 (3) [M+], 262 (64), 183 (100), 108 (72), 77
(7), 57 (8), 51 (27), 39 (11).
Palladium(0)-Catalyzed Allylic Substitution of 2,2 ,6,6 -Tet-
rahydroxybiphenyl (26)
A mixture of mesylate 6b (1296 mg, 8 mmol), Pd(dba)2 (28.75 mg,
0.048 mmol) and PPh3 (31.44 mg, 0.120 mmol) in anhyd DMF (40
HRMS: m/z calcd for C17H16NaO4 (M + Na): 307.0946; found
307.0943.
Synthesis 2002, No. 15, 2271–2279 ISSN 0039-7881 © Thieme Stuttgart · New York

2278
G. Delogu et al.
PAPER
Palladium(0)-Catalyzed Allylic Substitution of 6,6 -Dibromo-
2,2 -dihydroxy-3,3 -dimethoxybiphenyl
2,2 -Dihydroxy-6,6 -dimethoxy-3-[1-(2-trimethylsilylethenyl)-
cyclopropyl)]biphenyl (34)
A solution of Pd(dba)2 (44 mg, 0.0765mmol) and PPh3 (49 mg,
0.184 mmol) was degassed under vacuum for 1 h and stirred in a N2
atmosphere, then 1-ethenyl-1-tosyloxycyclopropane 6c (360 mg,
1.53 mmol) in anhyd DMF (15 mL) was added. After 10 min this
mixture had turned green and a solution of the potassium salt 31
[0.66 mmol, generated from 6,6 -dibromo-2,2 -dihydroxy-3,3 -
dimethoxybiphenyl23 (260 mg, 0.66 mmol), and K2CO3 (0.180 mg,
1.35 mmol) in DMF (10 mL, for 1 h at 60 °C)] was added, and the
mixture stirred at r.t. for 3 h. After addition of Et2O (20 mL) and sat.
NH4Cl (20 mL), the organic phase was extracted with Et2O (2 20
mL) and dried over Na2SO4. Removal of the solvent in vacuo and
flash chromatography (C5H12–Et2O, 8:2) of the residue gave the
pure product 32 (260 mg, 75%).
Colorless oil (9 mg, 90%).
IR (CDCl3): 3546, 2957, 2928, 2855, 1721, 1607, 1587, 1467 cm–1.
1H NMR (CDCl3): =0.10 (s, 9 H), 0.80–1.10 (m, 4 H), 3.73 (s, 3
H), 3.77 (s, 3 H), 5.07 (s, 1 H), 5.31 (d, 1 H, J = 18.1 Hz), 5.37 (s, 1
H), 5.59 (d, 1 H, J = 18.1 Hz), 6.59 (d, 2 H, J = 8.4 Hz), 6.68 (d, 1
H, J = 8.4 Hz), 7.18 (d, 1 H, J = 8.4 Hz), 7.27 (d, 1 H, J = 8.4 Hz).
13C NMR (CDCl3): = –0.64, 15.52, 15.71, 30.09, 56.25, 56.38,
103.24, 103.76, 107.31, 109.14, 120.99, 127.09, 128.97, 129.92,
131.99, 150.65, 154.66, 154.76, 157.37, 158.17.
MS (EI) m/z (%) = 384 (4) [M+], 370 (11), 311 (52), 167 (70), 149
(100).
2,2 -Bis(2-cyclopropylideneethoxy)-6,6-dibromo-3,3 -dimeth-
oxybiphenyl (32)
Acknowledgement
Colorless oil.
This work was financially supported by the CNRS (France) and the
CNR (Italy) within a French-Italian Cooperation Programme.
IR (CDCl3): 3060, 3008, 2938, 2839, 1571, 1460, 1436, 1368 cm–1.
1H NMR (CDCl3): = 0.82–0.94 (m, 8 H), 3.88 (s, 6 H), 4.55 (m, 4
H), 5.75 (m, 2 H), 6.86
References
(d, 2 H, J = 8.4 Hz), 7.48 (d, 2 H, J = 8.4 Hz).
13C NMR (CDCl3): = 1.53, 2.11, 55.87, 73.33, 113.05, 114.62,
114.84, 126.51, 127.03, 133.97, 147.25, 152.31.
MS (EI) m/z (%) = 534 (5) [M+], 322 (41), 309 (100), 214(95), 133
(41), 44 (82).
(1) (a) Tanaka, T.; Kouno, I. J. Nat. Prod. 1996, 59, 997.
(b) Li, H.-Y.; Nehira, T.; Hagiwara, M.; Harada, N. J. Org.
Chem. 1997, 62, 7222. (c) Charlton, J. L. J. Nat. Prod. 1998,
61, 1448. (d) Glombitza, K.-W.; Schmidt, A. J. Nat. Prod.
1999, 62, 1238. (e) Bringmann, G.; Breuningm, M.; Tasler,
S. Synthesis 1999, 525.
(2) (a) Uchida, I.; Shigematsu, N.; Ezaki, M.; Hashimoto, M.;
Aoki, H.; Imanaka, I. J. Antibiot. 1985, 38, 1462.
Palladium(0)-Catalyzed Substitution of 1-Tosyloxy-1-1(2-tri-
methylsilylethenyl)cyclopropane by the Dipotassium Salt 17 of
2,2 -Dihydroxy-6,6 -dimethoxybiphenyl
(b) Fujihashi, T.; Hara, H.; Sakata, T.; Mori, K.; Higuchi, H.;
Tanaka, A.; Kaji, H.; Kaji, A. Antimicrob. Agents
A solution of Pd(dba)2 (37 mg, 0.0645 mmol) and PPh3 (40 mg, 0.15
mmol) was degassed under vacuum for 1 h and stirred in a N2 atmo-
sphere, then 1-tosyloxy-1-1(2-trimethylsilylethenyl)cyclopropane
6d (380 mg, 1.29 mmol) in 15 ml of anhyd DMF was added. After
10 min this mixture had turned green and a solution of the dipotas-
sium salt 17 (generated as above ) was added, and the mixture
stirred at r.t. for 3 h; After addition of Et2O (20 mL) and sat. NH4Cl
(20 mL), the organic phase was extracted with Et2O (2 20 mL) and
dried over Na2SO4. Removal of the solvent in vacuo and flash chro-
matography (C5H12–Et2O, 6:4) of the residue gave a 60:40
diastereomeric mixture of 33 (50 mg, 25%).
Chemother. 1995, 39, 2000. (c) Nicolaou, K. C.; Boddy, C.
N.; Bräse, S.; Wissinger, N. Angew. Chem. Int. Ed. 1999, 38,
2096. (d) Baumeinster, B.; Sakai, N.; Gerard, D.; Matile, S.
Angew. Chem. Int. Ed. 2000, 39, 1955. (e) Itoh, T.;
Shirakami, S.; Ishida, N.; Yamashita, Y.; Yoshida, T.; Kim,
H.-S.; Wataya, Y. Bioorg. Med. Chem. Lett. 2000, 20, 1657.
(f) Tohma, H.; Morioka, H.; Takizawa, S.; Arisawa, M.;
Kita, Y. Tetraahedron 2001, 57, 345. (g) Bringmann, G.;
Tasler, S. Tetrahedron 2001, 57, 331. (h) For a review on
conformationally flexible biphenyls and their uses in
stoichiometric and catalytic processes see: Delogu, G.;
Vallee, Y. In Recent Research and Developments in Organic
Chemistry; Pandalai, S. G., Ed.; Transworld Research: India,
2002, 1–39.
2-[(2-Cyclopropylidene-1-trimethylsilyl)ethoxy]-6,6-dimeth-
oxy-2 -hydroxybiphenyl (33)
Colorless oil.
IR (CDCl3): 3541, 2958, 2928, 2855, 1589, 1465, 1247, 1090 cm–1.
1H NMR (CDCl3): = –0.15 (s, 9H), 0.92–1.04 (m, 4 H), 3.72 (s, 3
H), 3.74 (s, 3 H), 4.93 (s, 1 H), 5.70 (m, 1 H), 6.50–6.65 (m, 4 H),
7.17–7.27 (m, 2 H).
13C NMR (CDCl3): = –3.76, 0.46, 2.37, 2.92, 56.02, 56.35, 103.09,
103.79, 104.78, 106.42, 108.31, 109.74, 113.90, 116.98, 118.58,
121.65, 123.65, 128.94, 129.75, 138.79.
(3) (a) Brady, J. D.; Sadler, I. H.; Fry, S. C. Phytochemistry
1998, 47, 349. (b) Song, Q.; Fronczek, F. R.; Fischer, N. H.
Phytochemistry 2000, 55, 653. (c) Tene, M.; Wabo, H. K.;
Hamnaing, P.; Tsopmo, A.; Tane, P.; Ayafor, J. F.; Sterner,
O. Phytochemistry 2000, 54, 975.
(4) (a) Mazaleyra, J.-P.; Gaucher, A.; Avrda, J.; Wakselman, M.
Tetrahedron: Asymmetry 1997, 8, 619. (b) Gaucher, A.;
Bintein, F.; Wakselamn, M.; Mazaleyrat, J.-P. Tetrahedron
Lett. 1998, 39, 575. (c) Brandmeier, V.; Feigel, M.; Bremer,
M. Angew. Chem., Int. Ed. Engl. 1989, 28, 486.
MS (EI) m/z (%) = 384.2 (7) [M+], 369 (71), 311(100), 263(95),
(5) (a) Salaün, J. In The Chemistry of the Cyclopropyl Group;
Rappoport, Z., Ed.; Wiley: New York, 1987, Chap. 13, 809–
878. (b) In Houben-Weyl, Methods of Organic Chemistry,
Vol. E17a-f; de Meijere, A., Ed.; Thieme: Stuttgart, 1997.
(c) Salaün, J. Top. Curr. Chem. 1988, 144, 1.
187(22), 73(10).
Claisen Rearrangement of 33
A solution of 10 mg of the minor diastereomer 34 was kept at r.t. for
several weeks in CDCl3. After removal of the solvent in vacuo, flash
chromatography (C5H12–Et2O, 6:4) of the residue gave pure 34.
(6) (a) Salaün, J.; Baird, M. S. Curr. Med. Chem. 1995, 2, 511.
(b) Salaün, J. Top. Curr. Chem. 2000, 207, 1.
(7) Shizuri, Y.; Yamada, K. Phytochemistry 1985, 24, 1385.
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(8) (a) Henick, C. A.; Willy, W. E.; Staal, G. B.; Ludvik, G. F.
(13) For reviews see: (a) Binger, P.; Büch, H. M. Top. Curr.
Chem. 1987, 135, 77. (b) Goti, A.; Cordero, F. M.; Brandi,
A. Top. Curr. Chem. 1996, 178, 1.
J. Agric. Food Chem. 1976, 24, 1023. (b) Janiak, S. CIBA
Ltd., Ger., Offen. 1911520, 1968 CA 72: 21484n.
(9) Wright, S. W.; Harris, R. R.; Kerr, J. S.; Green, A. M.; Pinto,
D. J.; Bruin, E. M.; Collins, R. J.; Dorow, R. L.; Montegna,
L. R.; Sherk, S. R.; Covington, M. B.; Nurnberg, S. A.;
Welch, P. K.; Nelson, M. J.; Magolda, R. L. J. Med. Chem.
1992, 35, 4961.
(10) Blanc, M.; Tamir, A.; Aubriot, S.; Michel, M. C.;
Bouzoubaa, M.; Leclerc, G.; Demerge, P. J. Med. Chem.
1998, 41, 1613.
(14) Salaün, J. Chem. Rev. 1983, 83, 619.
(15) Salaün, J. Chem. Rev. 1989, 89, 1247.
(16) Sylvestre, I.; Ollivier, J.; Salaün, J. Tetrahedron Lett. 2001,
42, 4991.
(17) (a) Delogu, G.; Fabbri, D. Tetrahedron: Asymmetry 1997, 8,
759. (b) Delogu, G.; Fabbri, D.; Dettori, M. A. Tetrahedron:
Asymmetry 1998, 9, 2819.
(18) Suarez, M.; Bonilla, J.; de Diaz, A. M. P.; Achenbach, H.
Phytochemistry 1983, 22, 609; and references cited therein.
(19) Ogata, M.; Hoshi, M.; Urano, S.; Endo, T. Chem. Pharm.
Bull. 2000, 48, 1467; and references cited therein.
(20) Fujita, S.; Taira, J. Free Radical Biol. Med. 1994, 17, 273;
and references cited therein.
(21) Taira, T.; Takeschi Iketmoto, T.; Yoneya, T.; Hagi, A.;
Murakami, A.; Makino, K. Free Radical Res. Commun.
1992, 6, 197; and references cited therein.
(22) (a) Frater, G.; Schmid, H. Helv. Chim. Acta 1970, 53, 269.
(b) Falshaw, C. P.; Lane, S. A.; Ollis, W. D. J. Chem. Soc.,
Chem. Commun. 1973, 491.
(23) Delogu, G.; Fabbri, D.; Dettori, M. A.; Casalone, G.; Forni,
A. Tetrahedron: Asymmetry 2000, 11, 1827.
(24) (a) Frater, G.; Schmid, H. Helv. Chim. Acta 1970, 53, 269.
(b) Falshaw, C. P.; Lane, S. A.; Ollis, W. D. J. Chem. Soc.,
Chem. Commun. 1973, 491.
(11) (a) Stolle, A.; Ollivier, J.; Piras, P. P.; Salaün, J.; de Meijere,
A. J. Am. Chem. Soc. 1992, 114, 4051. (b) Ollivier, J.;
Dorizon, P.; Piras, P. P.; de Meijere, A.; Salaün, J. Inorg.
Chim. Acta 1994, 222, 37. (c) Salaün, J. Russ. J. Org. Chem.
1997, 33, 742. (d) Ollivier, J.; Girard, N.; Salaün, J. Synlett
1999, 1539. (e) Paschetta, V.; Cordero, F. M.; Paugam, R.;
Ollivier, J.; Brandi, A.; Salaün, J. Synlett 2001, 1233.
(12) (a) Chevtchouk, T.; Ollivier, J.; Salaün, J. Tetrahedron:
Asymmetry 1997, 8, 1005. (b) Chevtchouk, T.; Ollivier, J.;
Salaün, J. Tetrahedron : Asymmetry 1997, 8, 1011.
(c) Stolle, A.; Becker, H.; Salaün, J.; de Meijere, A.
Tetrahedron Lett. 1994, 35, 3517. (d) Stolle, A.; Becker, H.;
Salaün, J.; de Meijere, A. Tetrahedron Lett. 1994, 35, 3521.
(e) Atlan, V.; Racouchot, S.; Rubin, M.; Bremer, C.;
Ollivier, J.; de Meijere, A.; Salaün, J. Tetrahedron:
Asymmetry 1998, 9, 1131. (f) Estieu, K.; Paugam, R.;
Ollivier, J.; Salaün, J.; Cordero, F. M.; Goti, A.; Brandi, A.
J. Org. Chem. 1997, 62, 8276. (g) Ferrara, M.; Cordero, F.
M.; Goti, A.; Brandi, A.; Estieu, K.; Paugam, R.; Ollivier, J.;
Salaün, J. Chem. –Eur. J. 1999, 2725. (h) Pisaneschi, F.;
Cordero, F. M.; Goti, A.; Paugam, R.; Ollivier, J.; Brandi,
A.; Salaün, J. Tetrahedron: Asymmetry 2000, 11, 897.
(i) Cordero, F. M.; Pisaneschi, F.; Goti, A.; Ollivier, J.;
Salaün, J.; Brandi, A. J. Am. Chem. Soc. 2000, 122, 8075.
Synthesis 2002, No. 15, 2271–2279 ISSN 0039-7881 © Thieme Stuttgart · New York