Syntheses of Cyclic Bisbibenzyl Systems

Article abstract of DOI:10.1002/(SICI)1099-0690(199805)1998:5<877::AID-EJOC877>3.0.CO;2-S

The cyclic bisbibenzyl systems Marchantin I (3), Riccardin C (4) and Isoplagiochin C (5) representing unique types of bryophyte constituents were prepared by a flexible, efficient and general synthetic approach involving the construction of biphenyl and bibenzyl units using Suzuki and Wittig protocols.

Full text of DOI:10.1002/(SICI)1099-0690(199805)1998:5<877::AID-EJOC877>3.0.CO;2-S

FULL PAPER
Bryophyte Constituents, 9[᭛]
Syntheses of Cyclic Bisbibenzyl Systems
Theophil Eicher*, Sabine Fey, Werner Puhl, Edwin Büchel and Andreas Speicher*
Fachbereich 11, Organische Chemie, Universität des Saarlandes,
D-66041 Saarbrücken, Germany
Fax: (internat.) ϩ 49(0)681/302-2409
E-mail: anspeich@rz.uni-sb.de
Received November 17, 1997
Keywords: Natural products / Bryophyte constituents / Macrocycles / Bisbibenzyls / Total synthesis
The cyclic bisbibenzyl systems Marchantin I (3), Riccardin
and general synthetic approach involving the construction of
C (4) and Isoplagiochin C (5) representing unique types of biphenyl and bibenzyl units using Suzuki and Wittig proto-
bryophyte constituents were prepared by a flexible, efficient
cols.
arise[5]. The syntheses of bisbibenzyls are reviewed in ref.[3]
;
Introduction
except for the synthesis of Perrottetins[6], they in toto exhi-
Bisbibenzyl systems (Perrottetins, Marchantins, Riccar-
dins, Plagiochins) are structurally simple phenolic natual
products, which are found exclusively in bryophytes and ex-
bit serious preparative disadvantages (e.g. ref.[7][8]).
We report on flexible, efficient and general synthetic ap-
hibit remarkable biological activities[1][2][3]. They are con- proaches to the different types of cyclic bisbibenzyls, which
structed from two units of Lunularin (1), which can be com- are exemplified for syntheses of Marchantin I (3), Riccardin
bined by several modes (Scheme 1). OϪC attachment leads C (4) and Isoplagiochin C (5) providing the natural products
to acyclic (Perrottetins, e.g. 2) or cyclic systems (Marchan- on preparative scale[9]. In a convergent strategy, suitably
tins, e.g. 3) containing diphenyl ether units, OϪC and substituted diphenyl ether or biphenyl building blocks are
CϪCattachment leads to macrocycles of the Riccardin (e.g. prepared, possessing free or acetal-protected aldehyde func-
4) or Plagiochin type[4] containing diphenyl ether and bi- tions as well as ester or methyl groups transformable to a
phenyl units; if only CϪC attachment occurs systems of benzylphosphonium moiety. Formation of the bibenzyl
the Isoplagiochin type (e.g. 5) containing two biphenyl units bridges and cyclization is achieved by inter- and intramo-
Scheme 1. Variants of bisbibenzylic bryophyte constituents
lecular Wittig reaction and subsequent hydrogenation, fi-
nally the phenolic protective groups have to be removed.
[᭛]
Part 8: T. Eicher, M. Wobido, A. Speicher, J. Prakt. Chem. 1996,
338, 706Ϫ710.
Eur. J. Org. Chem. 1998, 877Ϫ888
WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1998
1434Ϫ193X/98/0505Ϫ0877 $ 17.50ϩ.50/0
877

T. Eicher, S. Fey, W. Puhl, E. Büchel, A. Speicher
FULL PAPER
Results and Discussion
Thus, Marchantin I (3) is obtained by convergence in 8
steps and 35% yield, from 10 in 15 steps and an overall
yield of 10%[7]
.
The synthesis of Marchantin I (3) starts with the Ullmann
coupling of the protected 2-bromo-5-methoxybenzaldehyde
Scheme 3. Synthesis of Marchantin I (3; Bzl ϭ C6H5ϪCH2)
6
[10][11] with 3-hydroxybenzaldehyde (7) resulting in the for-
mation of the diphenyl ether 8 (Scheme 2). As second di-
phenyl ether building block the phosphonium salt 16 is syn-
thesized in a conventional sequence starting with SNAr dis-
placement at methyl 4-chloro-3-nitrobenzoate (9) by 2-
methoxy-5-methylphenol (10) to give the diphenyl ether 11,
followed by catalytic reduction of the nitro group to the
amine 12 and its reductive deamination by diazotation in
H3PO2 to give 13. Finally, exchange of the phenolic protec-
tive group by methoxy cleavage with AlCl3 to give the phe-
nol 14 and benzoylation to give 15, followed by NBS bro-
mination of 15 and reaction with triphenylphosphane af-
forded 16 in 7 steps and 28% overall yield.
Scheme 2. Synthesis of the building block 16
For the synthesis of Riccardin C (4) the diphenyl ether
building block 31 and the biphenyl building block 37 are
required. The diphenyl ether aldehyde 31 is obtained by
SNAr reaction of 9 with isovanilline (24) in a sequence 25
Ǟ 31 (Scheme 4) similar to the foregoing synthesis of 13
and additional transformation of the ester group into a free
aldehyde function.
The building units 8 and 16 are combined by Wittig reac-
The biphenyl phosphonium salt 37 bearing an ester func-
tion in the presence of K2CO3/18-crown-6[12] and the stil- tion is obtained by Suzuki reaction[13][14][15] of the triflate
bene 17 obtained as (E/Z) mixture is hydrogenated cata- 35 derived from methyl 4-hydroxy-3-methoxybenzoate (33)
lytically (Pd/C) to give the bibenzyl 18 (Scheme 3). Reaction with the boronic acid 34 derived from 4-bromo-3-methylan-
of 18 with LiAlH4 results in reduction of the carboxylic isol (32) catalyzed by Pd0 to give 36, NBS bromination of
ester as well as removal of the benzoyl group and yields the 36 and reaction with triphenylphosphane (Scheme 5).
benzyl alcohol 19, in which the free phenolic OH group is
Again, for convergence the building units 31 and 37 are
protected by benzylation (Ǟ 20). When 20 is treated with subjected to a Wittig reaction in the presence of K2CO3/
HBr/acetic acid the dioxolane is cleaved and the benzyl bro- 18-crown-6 and the resulting stilbene 38 obtained as (E/Z)
mide 21 is formed; triphenylphosphane gives rise to the mixture is hydrogenated to the bibenzyl 39 (Scheme 6). Re-
benzyl phosphonium salt 22 bearing a free aldehyde func- duction of the carboxylic ester function with LiAlH4 gives
tion, the key intermediate of the synthesis. Cyclization of rise to the benzyl alcohol 40, treatment of 40 with HBr,
22 by means of an intramolecular Wittig reaction is followed by triphenylphosphane, transforms to the benzyl-
achieved with NaOCH3 leading to the (E)-stilbene 23, phosphonium functionality and generates the free aldehyde
which by catalytic hydrogenation and concomitant hydro- group by acid cleavage of the dioxolane moiety. The bifunc-
genolytic debenzylation yields the natural product 3.
tional phosphonium salt 41 is readily cyclized in an intra-
878
Eur. J. Org. Chem. 1998, 877Ϫ888

Bryophyte Constituents, 9
FULL PAPER
Scheme 4. Synthesis of the building block 31
Scheme 6. Synthesis of Riccardin C (4)
Scheme 5. Synthesis of the building block 37 (Tf ϭ ϪSO2CF3)
Scheme 7. Synthesis of the building block 47
molecular carbonyl olefination reaction using NaOCH3 to
give the (E/Z)-stilbene 42, which is hydrogenated to the tri-
methyl ether 43 of Riccardin C. Demethylation by means of
BBr3 yielded the natural product 4.
Thus, Riccardin C (4) is obtained by convergence in 8
As in the syntheses before, the two building units 47 and
steps and 35% yield, from 24 in 12 steps and an overall 37 are linked by Wittig reaction (K2CO3/18-crown-6) yield-
yield of 12%[8]
.
ing the stilbene 48 as (E/Z) mixture, followed by catalytic
For the synthesis of Isoplagiochin C (5) a further biphenyl hydrogenation to the bisbibenzyl 49 (Scheme 8). The car-
building block 47 was prepared by Suzuki reaction between boxylic ester group is reduced to the primary alcohol (Li-
the 1,3-dioxane 45 of 3-bromo-4-methoxybenzaldehyde 44 AlH4) with additional acidic cleavage of the 1,3-dioxane
and the aldehyde-functionalized boronic acid 46 obtained protective function (Ǟ 50) and transformed (PBr3/tri-
from 45 (Scheme 7).
phenylphosphane) to the benzyl phosphonium moiety in
Eur. J. Org. Chem. 1998, 877Ϫ888
879

T. Eicher, S. Fey, W. Puhl, E. Büchel, A. Speicher
FULL PAPER
raphy: RP-18 (Macherey-Nagel Polygoprep 60Ϫ50 C18). Ϫ Cata-
lytic hydrogenation: Parr Hydrogenation Apparatus. Ϫ Solvents
were commonly dried and purified by conventional methods prior
to use. All air- or moisture-sensitive reactions were carried out by
inert gas techniques under nitrogen.
Scheme 8. Synthesis of Isoplagiochin C (5) and Isoplagiochin D 54
General Procedure 1 (GP 1) for the Catalytic Hydrogenation of
Nitroarenes, Stilbenes and Benzyl Ethers
The nitroarene/stilbene/benzyl ether was dissolved in ethyl ace-
tate or methanol (100Ϫ300 ml), palladium on activated carbon
(5Ϫ10% Pd) was added (50 mg/mmol) and the hydrogenation per-
formed at 3Ϫ5 bar hydrogen pressure. The catalyst was filtered off
and the solvent removed in vacuo.
General Procedure 2 (GP 2) for the Preparation of Phosphonium
Salts from Methylarenes, Benzyl Alcohols or Benzoic Esters
GP 2.1 for the Bromination of Methylarenes Using N-Bromosuc-
cinimide: The methylarene in CCl4 (5 ml/mmol) was heated to re-
flux for 2 h in presence of 1 equiv. NBS and a trace of AIBN. The
mixture was cooled, the succinimide was filtered off and the solvent
evaporated in vacuo.
GP 2.2 for the Reduction of Esters (e.g. Benzoic Esters to Benzyl
Alcohols): To a suspension of an excess of LiAlH4 in diethyl ether
(10 ml/mmol) was added dropwise the ester to be reduced in diethyl
ether (10 ml/mmol). The mixture was refluxed for 5 h and carefully
hydrolysed with satd. NH4Cl. The aqueous layer was extracted sev-
eral times with diethyl ether and the combined organic layers dried
(MgSO4) and concentrated.
GP 2.3 for the Preparation of Phosphonium Salts from Benzyl
Halides: The benzyl halide was dissolved in toluene or acetonitrile
(5 ml/mmol) together with 1 equiv. of triphenylphosphane and
heated to 100°C for 15 h. Usually, the phosphonium salt was fil-
tered off, washed with petroleum ether and dried.
General Procedure 3 (GP 3) for the Wittig Reactions
GP 3.1 for Intermolecular Reaction Using K2CO3/18-Crown-6 in
Dichloromethane: The aldehyde and the phosphonium salt (1.05
equiv.) were dissolved in CH2Cl2 (10 ml/mmol), anhydrous K2CO3
(1.05 equiv.) and a small amount of 18-crown-6 were added and
the mixture refluxed for 24 h. The insoluble material was filtered
off and the filtrate concentrated in vacuo. The crude material was
purified by CC (normally SiO2; CH2Cl2).
51. Finally, the bifunctional aldehyde phosphonium salt 51
is cyclized by intramolecular Wittig reaction (NaOCH3).
The tetramethyl ether 52 of Isoplagiochin C, bearing exclus-
ively cis-stilbene geometry, can be demethylated by means
of BBr3 to give the natural product 5 or hydrogenated (Ǟ
53), followed by demethylation to give the saturated system
54, which also is found as a constituent of bryophytes called
GP 3.2 for Intramolecular Reaction Using NaOCH3 in Dichloro-
methane: To sodium methoxide (2 equiv.) in CH2Cl2 (50 ml/mmol)
the phosphonium salt in CH2Cl2 (150 ml/mmol) was added drop-
wise (5 h/mmol). Stirring was continued for 15 h at 20°C and the
mixture refluxed for 1 h. Insoluble material was filtered off, the
solvent was removed in vacuo and the residue purified by CC (nor-
mally SiO2; CH2Cl2).
Isoplagiochin D[16]
.
The above sequence makes possible for the first time the
synthesis of cyclic bisbibenzyls of the isoplagiochin type.
Isoplagiochin C (5) is obtained from convergence in 8 steps
and 29% yield, Isoplagiochin D (54) in 9 steps and 25%
yield; the total yields from 44 over 11 (12) steps are 18%
and 16%, respectively.
General Procedure 4 (GP 4) for the Cleavage of Aryl Methyl Ethers
To the aryl methyl ether in CH2Cl2 (2 ml/mmol) was added drop-
wise BBr3 (1  solution in CH2Cl2, 2Ϫ3 equiv. per methyl ether to
be cleaved) at Ϫ78°C or 0°C. Stirring was continued for 3 h at this
temperature and the mixture allowed to warm up to 20°C within
15 h. Ice-cold water was added dropwise and the product isolated
by filtration or extraction with a suitable solvent.
Experimental Section
General: IR: Beckmann Acculab 8. Ϫ UV: Varian DMS 80. Ϫ
1H NMR (400 MHz) and 13C NMR (100 MHz): Bruker AM 400
(TMS as internal standard). Ϫ MS: Finnigan MAT 90 (CI 120 eV)
or Varian MAT 311 (EI 70 eV). Ϫ Microanalyses: Leco CHNS-
932. Ϫ Thin layer chromatography (TLC): Merck aluminium roll
3-[2-(1,3-Dioxolan-2-yl)-4-methoxyphenoxy]benzaldehyde (8): A
0.2 mm (silica gel 60 F254 or alumina 60 F254 neutral type E). Ϫ mixture of 10.4 g (40.0 mmol) of 4-bromo-3-(1,3-dioxolan-2-yl)-
Column chromatography (CC): Silica gel (J. T. Baker 63Ϫ200 µm); phenyl methyl ether (6), 6.10 g (50.0 mmol) of 3-hydroxybenzal-
alumina (Fluka type 5016 A basic, activity I). Ϫ Flash chromatog-
dehyde (7), 6.90 g (50.0 mmol) of K2CO3 and 2.00 g (25.2 mmol)
880
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Bryophyte Constituents, 9
FULL PAPER
of CuO in 40 ml of pyridine was heated to reflux for 24 h. The
pyridine was distilled off in vacuo and the residue taken off in 200
ml of ethyl acetate discarding insoluble material. The crude mate-
ether. The combined organic layers were dried (MgSO4) and con-
centrated to give the crude arene which was filtered through an
SiO2 pad eluting with CH2Cl2 and recrystallized from ethanol;
rial after evaporation of the solvent was purified by CC (alumina; yield 11.4 g (84%), colourless crystals, m.p. 90°C. Ϫ IR (KBr): ν˜ ϭ
1
diethyl ether/petroleum ether, 2:1); yield 7.21 g (60%) of a slightly 2945, 1710 (COOCH3), 1610, 1585 cmϪ1. H NMR (CDCl3): δ ϭ
yellow oil. Ϫ IR (film): ν˜ ϭ 2875, 1700 (CHO), 1585, 1495, 1475
cmϪ1. Ϫ 1H NMR (CDCl3): δ ϭ 9.90 (s, 1 H, CHO), 7.53 (dd, H, Ar-H), 6.92Ϫ6.87 (m, 4 H, Ar-H), 3.86 (s, 3 H, COOCH3), 3.73
J1 ϭ 6.3 Hz, J2 ϭ 1.6 Hz, 1 H, Ar-H), 7.44 (t, J ϭ 8.0 Hz, 1 H,
(s, 3 H, OCH3), 2.27 (s, 3 H, CH3). Ϫ 13C NMR (CDCl3): δ ϭ
7.97Ϫ7.94 (m, 2 H, Ar-H), 6.98 (dd, J1 ϭ 8.5 Hz, J2 ϭ 2.0 Hz, 1
Ar-H), 7.38 (d, J ϭ 1.6 Hz, 1 H, Ar-H), 7.23Ϫ7.18 (not resolved, 166.66 (COOCH3), 162.43, 149.59, 143.27, 131.50, 131.15, 126.32,
2 H, Ar-H), 6.90 (mc, 2 H, Ar-H), 5.99 (s, 1 H, OCHO), 4.11Ϫ3.93 123.89, 123.00, 155.80, 113.27, 56.07 (OCH3), 51.78 (COOCH3),
(m, 4 H, OCH2CH2O), 3.82 (s, 3 H, OCH3). Ϫ 13C NMR (CDCl3): 20.43 (CH3). Ϫ MS; m/z (%): 272 (100) [Mϩ], 241 (30), 198 (46),
δ ϭ 191.57 (CϭO), 159.64, 156.71, 147.32, 138.06, 131.20, 130.28, 121 (10), 91 (7), 77 (7), 65 (7), 59 (10). Ϫ C16H16O4 (272.3): calcd.
123.90, 123.22, 121.91, 118.49, 117.08, 112.43, 99.28 (OCO), 65.37 C 70.58, H 5.92; found C 70.08, H 5.93.
(OCH2CH2O), 55.90 (OCH3). Ϫ MS; m/z (%): 300 (22) [Mϩ], 256
Methyl 4-(2-Hydroxy-5-methylphenoxy)benzoate (14): To a solu-
tion of 10.6 g (36.7 mmol) of the methyl ether 13 in 200 ml of
benzene was added batchwise 20.0 g (150 mmol) of anhydrous
(9), 169 (3), 135 (16), 97 (26), 86 (19), 84 (29), 51 (100), 49 (48). Ϫ
C17H16O5 (300.3): calcd. C 68.00, H 5.37; found C 67.90, H 5.29.
Methyl 4-(2-Methoxy-5-methylphenoxy)-3-nitrobenzoate (11): To
a suspension of 2.40 g (0.10 mol) of NaH in 50 ml of DMF was
AlCl3 and the slurry was refluxed for 15 h. After cooling, the mix-
ture was poured into 350 g of crushed ice, extracted three times
added dropwise 13.8 g (0.10 mol) of 2-methoxy-5-methylphenol with 200 ml of diethyl ether, dried (MgSO4) and concentrated in
(10) in 100 ml of DMF. After stirring for 10 min at 20°C, 21.6 g vacuo. The crude product was filtered through an SiO2 pad eluting
(0.10 mol) of methyl 4-chloro-3-nitrobenzoate (9) in 100 ml of
DMF was added dropwise with ice-cooling. The mixture was al-
lowed to warm up to 20°C and stirred for additional 2 h. After
evaporation of the solvent, the residue was taken up in 500 ml of
with diethyl ether/petroleum ether, 1:1, and recrystallized from
toluene/petroleum ether, 1:1; yield 7.70 g (81%), colourless crystals,
m.p. 102°C. Ϫ IR (film): ν˜ ϭ 3425 (OH), 2950, 1715 (COOCH3),
1
1605, 1590 cmϪ1. Ϫ H NMR (CDCl3): δ ϭ 7.93Ϫ7.89 (m, 2 H,
CHCl3, washed with each 300 ml of 2  NaOH, 2  HCl and H2O, Ar-H), 6.96Ϫ6.87 (m, 4 H, Ar-H), 6.76 (d, J ϭ 1.4 Hz, 1 H, Ar-
dried (MgSO4) and concentrated. The crude material was purified H), 5.78 (br. s, 1 H, OH), 3.86 (s, 3 H, COOCH3), 2.23 (s, 3 H,
by recrystallization from ethanol; yield 27.3 g (87%), slightly yellow CH3). Ϫ 13C NMR (CDCl3): δ ϭ 166.73 (COOCH3), 161.48,
needles, m.p. 65°C. Ϫ IR (KBr): ν˜ ϭ 2950, 2920, 1730 (COOCH3),
145.68, 141.73, 131.75, 130.61, 128.49, 124.61, 123.87, 121.10,
1620, 1515 (NO2), 1355 (NO2) cmϪ1. Ϫ 1H NMR (CDCl3): δ ϭ 166.76, 116.51, 52.05 (COOCH3), 20.12 (CH3). Ϫ MS; m/z (%):
8.60 (d, J ϭ 2.2 Hz, 1 H, Ar-H), 8.05 (dd, J1 ϭ 8.8 Hz, J2 ϭ 2.1 258 (100) [Mϩ], 227 (59) [Mϩ Ϫ OCH3], 128 (10), 92 (8), 77 (13),
Hz, 1 H, Ar-H), 7.05 (dd, J1 ϭ 8.4 Hz, J2 ϭ 2.0 Hz, 1 H, Ar-H), 65 (10), 50 (9). Ϫ C15H14O4 (258.3): calcd. C 69.76, H 5.46; found
6.97 (d, J ϭ 1.9 Hz, 1 H, Ar-H), 6.91 (d, J ϭ 8.3 Hz, 1 H, Ar-H),
6.80 (d, J ϭ 8.8 Hz, 1 H, Ar-H), 3.93 (s, 3 H, COOCH3), 3.72 (s,
3 H, OCH3), 2.31 (s, 3 H, CH3). Ϫ 13C NMR (CDCl3): δ ϭ 164.90
(COOCH3), 155.33, 149.09, 142.01, 139.26, 134.76, 131.55, 127.50,
127.31, 123.88, 123.06, 117.14, 113.55, 56.21 (OCH3), 52.46 (CO-
OCH3), 20.43 (CH3). Ϫ MS; m/z (%): 317 (32) [Mϩ], 286 (8) [Mϩ
Ϫ OCH3], 137 (100), 109 (80), 107 (10), 94 (15), 91 (32), 81 (18),
79 (14), 77 (16), 66 (17), 65 (14). Ϫ C16H15NO6 (317.3): calcd. C
60.57, H 4.77, N 4.41; found C 60.05, H 4.81, N 4.41.
C 69.07, H 5.29.
Methyl 4-(2-Benzoyloxy-5-methylphenoxy)benzoate (15): 10.0 g
(37.7 mmol) of the phenol 14 was dissolved in 150 ml of ethanol
and combined with a solution of 12.7 g (90.0 mmol) of Na2CO3 in
150 ml of H2O. 6.32 g (45.0 mmol) of benzoyl chloride was added
dropwise at 20Ϫ25°C and the mixture was stirred for 5 h at 20°C
and extracted three times with 200 ml of dichloromethane. The
organic layer was washed with 200 ml of H2O, dried (MgSO4) and
concentrated in vacuo. The crude product was filtered through an
SiO2 pad eluting with CH2Cl2 and recrystallized from methanol;
Methyl 3-Amino-4-(2-methoxy-4-methylphenoxy)benzoate (12):
15.0 g (50.0 mmol) of the nitroarene 11 was hydrogenated accord- yield 11.3 g (81%), colourless crystals, m.p. 62°C. Ϫ IR (KBr): ν˜ ϭ
ing to GP 1 (5% Pd/C, ethyl acetate, 5 bar, 6 h). Recrystallization 1750, 1730 (CϭO), 1605, 1510 cmϪ1. Ϫ 1H NMR (CDCl3): δ ϭ
from ethanol yielded 12.2 g (85%) of compound 12 as colourless 7.94Ϫ7.91 (m, 4 H, Ar-H), 7.53Ϫ7.51 (m, 1 H, Ar-H), 7.37 (t, J ϭ
crystals, m.p. 101°C. Ϫ IR (film): ν˜ ϭ 3460, 3365 (NH2), 1715 7.8 Hz, 2 H, Ar-H), 7.20 (d, J ϭ 8.2 Hz, 1 H, Ar-H), 7.06 (dd,
1
(COOCH3), 1625, 1600 cmϪ1 . Ϫ H NMR (CDCl3): δ ϭ 7.47 (d, J1 ϭ 8.2 Hz, J2 ϭ 1.7 Hz, 1 H, Ar-H), 6.96 Ϫ 6.93 (m, 3 H, Ar-
J ϭ 2.0 Hz, 1 H, Ar-H), 7.33 (dd, J1 ϭ 8.4 Hz, J2 ϭ 2.0 Hz, 1 H, H), 3.86 (s, 3 H, COOCH3), 2.35 (s, 3 H, CH3). Ϫ 13C NMR
Ar-H), 6.94 (dd, J1 ϭ 8.5 Hz, J2 ϭ 2.1 Hz, 1 H, Ar-H), 6.88 (d, (CDCl3): δ ϭ 166.53 (COOCH3), 164.52 (CϭO), 161.59, 146.60,
J ϭ 8.3 Hz, 1 H, Ar-H), 6.80 (d, J ϭ 1.9 Hz, 1 H, Ar-H), 6.61 (d,
140.35, 137.42, 133.51, 131.58, 130.11, 129.06, 128.43, 126.04,
J ϭ 8.4 Hz, 1 H, Ar-H), 4.10Ϫ3.90 (br. s, 2 H, NH2), 3.85 (s, 3 H, 124.65, 123.93, 123.78, 122.43, 116.62, 51.89 (COOCH3), 21.00
COOCH3), 3.77 (s, 3 H, OCH3), 2.25 (s, 3 H, CH3). Ϫ 13C NMR (CH3). Ϫ MS; m/z (%): 362 (8) [Mϩ], 198 (2), 105 (100) [PhCOϩ],
(CDCl3): δ ϭ 167.04 (COOCH3), 147.17, 144.05, 137.04, 131.06, 77 (26), 50 (7), 42 (10). Ϫ C22H18O5 (362.4): calcd. C 72.92, H 5.01;
125.61, 124.98, 123.90, 121.73, 120.43, 116.88, 115.58, 113.10,
56.16 (OCH3), 51.81 (COOCH3), 20.15 (CH3). Ϫ MS; m/z (%): 287
(17) [Mϩ], 256 (27) [Mϩ Ϫ OCH3], 240 (18), 213 (51), 78 (12), 65
(11), 52 (11).
found C 72.64, H 4.93.
[4-Benzoyloxy-3-(4-methoxycarbonylphenoxy)]benzyl Triphenyl-
phosphonium Bromide (16): 5.00 g (13.8 mmol) of the methylarene
15 was brominated according to GP 2.1. From the crude benzyl
Methyl 4-(2-Methoxy-4-methylphenoxy)benzoate (13): To 14.4 g bromide the phosphonium salt was prepared according to GP 2.3
(50.0 mmol) of the aminoarene 12 dissolved in 100 g (75.0 mmol)
of 50% aq. H3PO2 and 80 ml of H2O was added dropwise 3.81 g
(toluene); yield 6.45 g (68%), colourless salt, m.p. 244°C (aceto-
nitrile). Ϫ IR (KBr): ν˜ ϭ 1735, 1720 (CϭO), 1590 cmϪ1. Ϫ 1H
(55.0 mmol) of NaNO2 in 20 ml of H2O at 0°C and stirring was NMR (CDCl3): δ ϭ 7.89 (dd, J1 ϭ 7.9 Hz, J2 ϭ 1.3 Hz, 2 H, Ar-
continued for 2 h at 0°C and for 5 h at 20°C. The mixture was H), 7.82Ϫ7.75 (m, 11 H, Ar-H), 7.64Ϫ7.56 (m, 7 H, Ar-H), 7.38
slightly alkalized using concd. NaOH and extracted with diethyl
(t, J ϭ 7.9 Hz, 2 H, Ar-H), 7.23 (d, J ϭ 8.3 Hz, 1 H, Ar-H), 7.02
Eur. J. Org. Chem. 1998, 877Ϫ888
881

T. Eicher, S. Fey, W. Puhl, E. Büchel, A. Speicher
(d, J ϭ 8.1 Hz, 1 H, Ar-H), 6.86 (t, J ϭ 2.2 Hz, 1 H, Ar-H), 6.68 NMR (CDCl3): δ ϭ 158.49, 156.54, 155.98, 148.50, 145.79, 143.31,
FULL PAPER
(d, J ϭ 1.7 Hz, 2 H, Ar-H), 5.58 (d, J( 31P-1H) ϭ 14.5 Hz, 2 H,
143.07, 136.03, 133.08, 130.33, 129.38, 128.69, 124.84, 123.47,
CH2P), 3.88 (s, 3 H, COOCH3). Ϫ 13C NMR (CDCl3): δ ϭ 166.39 122.88, 121.21, 120.69, 119.37, 117.98, 117.02, 116.67, 116.42,
(COOCH3), 164.33 (CϭO), 160.58, 147.42, 142.59, 135.08, 134.58, 116.29, 115.23, 112.07, 99.28 (O-CH-O), 65.35 (OCH2CH2O),
134.49, 133.80, 131.64, 130.34, 130.22, 130.11, 128.95, 128.90,
64.65 (CH2OH), 55.42 (OCH3), 37.73, 36.72 (ArCH2CH2Ar). Ϫ
128.73, 128.56, 127.31, 127.23, 125.22, 124.19, 118.23, 117.28, 51.97 MS; m/z (%): 514 (6) [Mϩ], 453 (11), 211 (21), 149 (21), 91 (17), 87
(COOCH3), 30.48, 30.02 (CH2P). Ϫ MS; m/z (%): 623 (1) [Mϩ
Ϫ
(22), 79 (9), 73 (17), 63 (43), 59 (25), 57 (27), 45 (100). Ϫ C31H30O7
Br], 525 (18), 445 (12), 381 (21), 367 (89), 262 (100) [PPh3ϩ], 213 (514.6): calcd. C 72.34, H 5.88; found C 72.02, H 5.79.
(3), 105 (4), 77 (1). Ϫ C40H32BrO5P (703.6): calcd. C 68.29, H 4.58;
[4-(2-Benzyloxy-5-{3-[2-(1,3-dioxolan-2-yl)-4-methoxy-
found C 68.37, H 4.51.
phenoxy]phenethyl}phenoxy)phenyl]methanol (20): 2.00 g (3.89
mmol) of the phenol 19, 0.49 g (3.89 mmol) of benzyl chloride and
0.54 g (3.89 mmol) of K2CO3 in 40 ml of DMF were stirred for 2
h at 120°C. The mixture was poured into 200 ml of H2O and ex-
tracted with CH2Cl2 (4 ϫ 100 ml). The organic layers were dried
(MgSO4) and concentrated and the residue purified by CC (SiO2;
diethyl ether); yield 2.07 g (88%), colourless oil. Ϫ IR (film): ν˜ ϭ
3440 (OH), 2930, 2880, 1585 cmϪ1. Ϫ 1H NMR (CDCl3): δ ϭ
7.27Ϫ7.13 (m, 9 H, Ar-H), 6.90Ϫ6.71 (m, 10 H, Ar-H), 5.99 (s, 1
H, OCHO), 5.02 (s, 2 H, CH2Ph), 4.59 (s, 2 H, CH2OH), 4.11Ϫ3.91
(m, 4 H, OCH2CH2O), 3.77 (s, 3 H, OCH3), 2.80 (s, 4 H, ArCH2-
CH2Ar), 2.02 (br. s, 1 H, OH). Ϫ 13C NMR (CDCl3): δ ϭ 158.55,
158.00, 156.01, 148.76, 148.48, 145.23, 143.31, 137.69, 135.39,
134.87, 130.37, 129.39, 128.47, 128.32, 127.68, 127.11, 124.79,
122.83, 122.07, 121.24, 117.74, 116.67, 116.39, 115.75, 115.23,
112.02, 99.26 (OCHO), 71.36 (OCH2Ph), 65.36 (OCH2CH2O),
64.93 (CH2OH), 55.69 (OCH3), 37.61, 36.64 (ArCH2CH2Ar). Ϫ
MS; m/z (%): 605 (8) [Mϩ], 561 (10), 344 (10), 302 (51), 279 (14),
258 (100), 240 (68), 225 (28), 211 (35), 167 (25), 149 (30), 124 (13),
111 (13), 91 (66), 71 (26), 43 (19). Ϫ C38H36O7 (604.7): calcd. C
75.48, H 6.00; found C 74.93, H 5.86.
Methyl 4-{2-Benzoyloxy-5-[(E/Z)-2-{3-[2-(1,3-dioxolan-2-yl)-
4-methoxyphenoxy]phenyl}-1-ethenyl]phenoxy}benzoate (17): Re-
action between the aldehyde 8 (3.28 g, 10.9 mmol) and the phos-
phonium salt 16 (8.07 g, 11.5 mmol) according to GP 3.1, followed
by CC (SiO2; CH2Cl2) yielded 6.27 g (89%) of 17 as a colourless
viscous oil. Ϫ IR (film): ν˜ ϭ 2940, 2875, 1745, 1720 (CϭO), 1600,
1
1580 cmϪ1. Ϫ H NMR (CDCl3): δ ϭ 7.96Ϫ7.89 (m, 4 H, Ar-H),
7.38Ϫ6.74 (m, 16 H, Ar-H, CHϭCH), 6.58 and 6.48 (d, J ϭ 12.2
Hz, 1 H, CHϭCH), 6.04 and 5.98 (s, 1 H, OϪCHϪO), 4.10Ϫ3.90
(m, 4 H, OϪCH2ϪCH2ϪO), 3.84 and 3.83 (s, 3 H, COOCH3),
3.78 and 3.76 (s, 3 H, OCH3). Ϫ 13C NMR (CDCl3): δ ϭ 166.36
(COOCH3), 164.20, 161.36, 161.09, 159.11, 158.71, 156.25, 156.13,
148.16, 148.02, 146.72, 141.42, 138.62, 138.35, 136.78, 136.34,
133.58, 131.58, 130.98, 130.75, 130.62, 130.08, 129.85, 129.65,
129.51, 129.15, 128.93, 128.44, 127.68, 125.83, 124.79, 124.36,
123.91, 123.59, 122.97, 122.02, 121.47, 120.97, 119.56, 117.57,
117.02, 116.88, 116.80, 116.70, 116.37, 115.40, 112.17, 99.26
(OCHO), 65.32 (OCH2CH2O), 55.86 (OCH3), 51.83 (COOCH3). Ϫ
MS; m/z (%): 645 (25) [Mϩ], 331 (8), 300 (86), 277 (34), 256 (100),
241 (34), 225 (48), 197 (96), 149 (32), 121 (46), 105 (99), 83 (35). Ϫ
C39H32O9 (644.7): calcd. C 72.66, H 5.00; found C 72.72, H 5.04.
2-(3-{4-Benzyloxy-3-[4-(bromomethyl)phenoxy]phenethyl}-
phenoxy)-5-methoxybenzaldehyde (21): 0.55 g (0.91 mmol) of the
benzyl alcohol 20 in diethyl ether was treated with 1 ml of 33%
HBr in acetic acid and stirred for 2 h at 20°C. The organic layer
was washed sufficiently with satd. NaHCO3, dried (MgSO4) and
concentrated. The resulting benzyl bromide was very sensitive and
converted directly .Ϫ IR (film): ν˜ ϭ 2940, 2865, 1695 (CHO), 1615,
Methyl
4-(2-Benzoyloxy-5-{3-[2-(1,3-dioxolan-2-yl)-4-meth-
oxyphenoxy]phenetyl}phenoxy)benzoate (18): 3.70 g (5.74 mmol) of
the stilbene 17 was hydrogenated according to GP 1 (5% Pd/C,
ethyl acetate, 5 bar, 12 h) in the presence of 7 ml of triethylamine.
Filtering through an SiO2 pad (eluent: CH2Cl2) yielded 3.49 g
(94%) of a colourless oil. Ϫ IR (film): ν˜ ϭ 2950, 2890, 1750, 1725
(CϭO), 1610, 1595 cmϪ1. Ϫ 1H NMR (CDCl3): δ ϭ 7.95Ϫ7.91
(m, 4 H, Ar-H), 7.55 (t, J ϭ 8.0 Hz, 1 H, Ar-H), 7.38 (t, J ϭ 7.8
Hz, 2 H, Ar-H), 7.23Ϫ7.15 (m, 3 H, Ar-H), 7.04 (dd, J1 ϭ 8.3 Hz,
J2 ϭ 1.9 Hz, 1 H, Ar-H), 6.91Ϫ6.74 (m, 8 H, Ar-H), 6.02 (s, 1 H,
OCHO), 4.14Ϫ3.95 (m, 4 H, OCH2CH2O), 3.87 (s, 3 H, COOCH3),
3.81 (s, 3 H, OCH3), 2.88 (s, 4 H, ArCH2CH2Ar). Ϫ 13C NMR
(CDCl3): δ ϭ 166.53 (COOCH3), 164.44 (CϭO), 161.50, 158.74,
156.10, 148.40, 146.58, 142.93, 141.00, 140.71, 133.52, 131.61,
130.51, 130.11, 129.52, 129.04, 128.43, 125.43, 124.67, 123.88,
122.75, 121.94, 121.38, 117.60, 116.73, 116.45, 115.35, 112.00,
99.30 (OCHO), 65.40 (OCH2CH2O), 55.70 (OCH3), 51.69 (CO-
OCH3), 37.40, 36.95 (ArCH2CH2Ar). Ϫ MS; m/z (%): 647 (3) [Mϩ],
479 (1), 285 (2), 225 (2), 194 (3), 149 (52), 125 (2), 111 (4), 105
(100) [PhCOϩ], 97 (6), 91 (7), 77 (19), 71 (7), 61 (7), 57 (13). Ϫ
C39H34O9 (646.7): calcd. C 72.43, H 5.30; found C 72.39, H 5.25.
1590 cmϪ1
.
2-[3-(4-Benzyloxy-3-{4-[(1,1,1-triphenylphosphonio)methyl]-
phenoxy}phenethyl)phenoxy]-5-methoxybenzaldehyde Bromide (22):
From the crude benzyl bromide 21 (0.91 mmol) the phosphonium
salt was prepared according to GP 2.3 (10 ml of toluene). The
supernatant toluene was decanted and the viscous residue washed
with 10 ml of toluene. Concentration in vacuo yielded 0.60 g (75%
from 20) of a beige salt, m.p. 175°C. Ϫ IR (KBr): ν˜ ϭ 2855, 1690
1
(CHO), 1610, 1585 cmϪ1. Ϫ H NMR (CDCl3): δ ϭ 10.33 (s, 1 H,
CHO), 7.75Ϫ7.67 (m, 10 H, Ar-H), 7.60Ϫ7.56 (m, 6 H, Ar-H),
7.11 (dd, J1 ϭ 8.9 Hz, J2 ϭ 3.1 Hz, 1 H, Ar-H), 7.01 (dd, J1 ϭ 8.8
Hz, J2 ϭ 2.5 Hz, 2 H, Ar-H), 6.91Ϫ6.71 (m, 6 H, Ar-H), 6.66 (d,
J ϭ 2.0 Hz, 2 H, Ar-H), 5.31 (d, J(31P-1H) ϭ 13.9 Hz, 2 H, CH2P),
5.02 (s, 2 H, CH2Ph), 3.81 (s, 3 H, OCH3), 2.81 (s, 4 H, ArCH2-
CH2Ar). Ϫ 13C NMR (CDCl3): δ ϭ 189.16 (CHO), 158.63, 157.81,
155.90, 153.54, 148.80, 144.47, 143.79, 136.95, 135.22, 134.98,
134.49, 134.39, 132.71, 130.29, 130.11, 129.92, 128.49, 127.84,
127.02, 125.28, 123.87, 123.60, 122.16, 121.47, 118.37, 118.26,
117.52, 116.98, 115.76, 115.52, 110.13, 71.12 (OCH2Ph), 55.90
(OCH3), 37.56, 36.63 (ArCH2CH2Ar), 30.50, 30.04 (CH2P). Ϫ
C54H46BrO5P (885.8): calcd. C 73.22, H 5.23; found C 72.95, H
5.01.
4-{3-[2-(1,3-Dioxolan-2-yl)-4-methoxyphenoxy]phenetyl}-2-[4-
(hydroxymethyl)phenoxy]phenol (19): 3.50 g (5.41 mmol) of the di-
ester 18 was reduced according to GP 2.2 (5.95 mmol of LiAlH4).
Purification by CC (SiO2; diethyl ether) yielded 2.40 g (86%),
colourless oil. Ϫ IR (film): ν˜ ϭ 3380 (OH), 1595 cmϪ1. Ϫ 1H NMR
(CDCl3): δ ϭ 7.24 (d, J ϭ 8.6 Hz, 2 H, Ar-H), 7.14Ϫ7.11 (m, 2 H,
Ar-H, 6.91Ϫ6.72 (m, 8 H, Ar-H), 6.65 (s, 1 H, Ar-H), 6.58 (d, J ϭ
2.0 Hz, 1 H, Ar-H), 5.97 (s, 2 H, OCHO, OH), 4.95 (s, 2 H,
Benzyl Ether of (E)-Dehydromarchantin I (23): 0.50 g (0.56
CH2OH), 4.10Ϫ3.90 (m, 4 H, OCH2CH2O), 3.78 (s, 3 H, OCH3), mmol) of the phosphonium salt 22 was subjected to a Wittig reac-
2.76Ϫ2.74 (m, 4 H, ArCH2CH2Ar), 2.42 (s, 1 H, CH2OH). Ϫ 13C tion according to GP 3.2; yield 0.24 g (81%), colourless crystals,
882
Eur. J. Org. Chem. 1998, 877Ϫ888

Bryophyte Constituents, 9
FULL PAPER
m.p. 164°C. Ϫ IR (KBr): ν˜ ϭ 3025, 2925, 1610, 1585 cmϪ1. Ϫ UV (331.3): calcd. C 58.01, H 3.96, N 4.23; found C 58.24, H 3.83,
(acetonitrile): λmax (log ε) ϭ 275 (3.87), 218 (4.19) nm. Ϫ 1H NMR N 4.66.
(CDCl3): δ ϭ 7.51Ϫ6.09 (m, 20 H, Ar-H, CHϭCH), 5.69 (d, J ϭ
Methyl 4-[5-(Diacetyloxymethyl)-2-methoxyphenoxy]-3-nitro-
2.0 Hz, 1 H, Ar-H), 5.23 (s, 2 H, CH2Ph), 3.87 (s, 3 H, OCH3),
benzoate (26): 33.1 g (0.10 mol) of the aldehyde 25 in 350 ml of
2.95Ϫ2.85 (m, 4 H, ArCH2CH2Ar). Ϫ 13C NMR (CDCl3): δ ϭ
acetic anhydride together with some drops of concd. H2SO4 was
159.28, 157.03, 155.59, 151.31, 146.51, 146.02, 142.93, 137.53,
stirred for 2 h at 20°C and the mixture was poured into crushed
137.27, 135.95, 132.04, 131.79, 128.57, 127.86, 127.45, 126.99,
ice. The product precipitating within 10 h was filtered off, washed
123.23, 122.80, 122.01, 119.31, 116.71, 115.27, 113.88, 112.90,
(H2O), dried in vacuo and recrystallized from ethanol; yield 37.4 g
111.28, 71.86 (CH2Ph), 55.73 (OCH3), 34.09, 30.87 (ArCH2-
(86%), yellow crystals, m.p. 107°C. Ϫ IR (KBr): ν˜ ϭ 3080, 3055,
CH2Ar). Ϫ MS; m/z (%): 527 (8) [Mϩ], 526 (16), 435 (8), 237 (12),
3020, 2995, 2950, 2845, 1770 (CH3COO), 1720 (COOCH3), 1625,
225 (6), 211 (49), 181 (7), 165 (6), 105 (12), 91 (100), 77 (11), 65
1585, 1535 (NO) cmϪ1. Ϫ 1H NMR (CDCl3): δ ϭ 8.63 (d, J ϭ 2.2
(14), 57 (17), 55 (11), 42 (17). Ϫ C36H30O4 (526.6): calcd. C 82.10,
Hz, 1 H, Ar-H), 8.08 (dd, J1 ϭ 8.8 Hz, J2 ϭ 2.2 Hz, 1 H, Ar-H),
H 5.74; found C 81.91, H 5.80.
7.63 (s, 1 H, OCHO), 7.43 (dd, J1 ϭ 8.5 Hz, J2 ϭ 2.1 Hz, 1 H, Ar-
H), 7.37 (d, J ϭ 2.1 Hz, 1 H, Ar-H), 7.04 (d, J ϭ 8.5 Hz, 1 H, Ar-
Marchantin I (3): 0.20 g (0.38 mmol) of the (E)-stilbene 23 was
H), 6.80 (d, J ϭ 8.8 Hz, 1 H, Ar-H), 3.94 (s, 3 H, COOCH3), 3.77
hydrogenated according to GP 1 (10% Pd/C, methanol, 5 bar, 15
(s, 3 H, OCH3), 2.13 (s, 6 H, CH3COO). Ϫ 13C NMR (CDCl3):
h). Purification by CC (SiO2; CH2Cl2) yielded 150 mg (90%),
δ ϭ 166.70 (CH3COO), 164.80 (COOCH3), 154.78, 152.29, 142.12,
colourless crystals, m.p. 135°C. Ϫ IR (KBr): ν˜ ϭ 3450 (OH), 2935,
139.27, 134.87, 129.21, 127.43, 125.92, 124.30, 120.95, 117.04,
2865, 1740, 1615, 1515, 1455, 1370, 1275, 1245, 1215, 1120, 1040,
113.09, 88.97 (O-CH-O), 56.16 (OCH3), 52.55 (COOCH3), 20.83
920, 820, 785, 740, 705 cmϪ1. Ϫ UV (ethanol): λmax (log ε): 273
(CH3COO). Ϫ MS; m/z (%): 433 (5) [Mϩ], 360 (9), 332 (24), 330
1
(1.64), 217 (4.14) nm. Ϫ H NMR (CDCl3): δ ϭ 7.04 (t, J ϭ 7.5
(18), 300 (13), 284 (5), 270 (5), 180 (7), 151 (35), 123 (5), 108 (8),
Hz, 1 H, Ar-H), 7.00 (d, J ϭ 8.3 Hz, 1 H, Ar-H), 6.92 (d, J ϭ 3.0
95 (14), 71 (10), 57 (13), 43 (100) [CH3COϩ]. Ϫ C20H19NO10
Hz, 2 H, Ar-H), 6.85 (d, J ϭ 8.1 Hz, 1 H, Ar-H), 6.78 (d, J ϭ 8.9
(433.4): calcd. C 55.43, H 4.42, N 3.23; found C 55.44, H 4.55,
Hz, 1 H, Ar-H), 6.72 (dd, J1 ϭ 8.1 Hz, J2 ϭ 1.8 Hz, 1 H, Ar-H),
N 3.27.
6.69 (dd, J1 ϭ 7.7 Hz, J2 ϭ 1.6 Hz, 1 H, Ar-H), 6.65 (dd, J1 ϭ 8.9
Hz, J2 ϭ 3.0 Hz, 1 H, Ar-H), 6.63 (d, J ϭ 8.4 Hz, 2 H, Ar-H),
Methyl 3-Amino-4-[5-(diacetyloxymethyl)-2-methoxyphenoxy]-
6.54 (d, J ϭ 7.3 Hz, 1 H, Ar-H), 6.53 (s, 1 H, Ar-H), 5.87 (d, J ϭ benzoate (27): 34.70 g (80.0 mmol) of the nitroarene 26 was hydro-
1.8 Hz, 1 H, Ar-H), 5.54 (s, 1 H, OH), 3.81 (s, 3 H, OCH3), 3.08 genated according to GP 1 (5% Pd/C, ethyl acetate, 5 bar, 4 h). The
Ϫ 2.98 (m, 4 H, ArCH2CH2Ar), 2.89 Ϫ 2.76 (m, 4 H, ArCH2-
crude yellow amine 27 was very sensitive and converted directly. Ϫ
CH2Ar). Ϫ 13C NMR (CDCl3): δ ϭ 157.09, 155.30, 153.53, 148.07, IR (film): ν˜ ϭ 3470, 3370 (NH2), 3060, 2980, 2945, 2835, 1765
145.56, 144.06, 142.78, 137.93, 133.60, 133.14, 129.88, 128.38,
123.84, 120.43, 118.64, 117.77, 116.18, 116.13, 115.31, 114.97,
111.89, 55.61 (OCH3), 36.77, 35.70, 34.38, 30.33 (ArCH2CH2Ar).
Ϫ MS; m/z (%): 439 (36) [Mϩ], 438 (81), 225 (37), 211 (100), 199
(11), 182 (9), 165 (12), 149 (14), 120 (11), 117 (71), 105 (27), 91
(42), 77 (29), 65 (12), 55 (13), 51 (10), 42 (13). Ϫ C29H26O4 (438.5):
calcd. C 79.94, H 5.98; found C 79.79, H 5.88. Ϫ The 1H-NMR
(CH3 COO), 1720 (COOCH3), 1625, 1600 cmϪ1
.
Methyl 4-(5-Formyl-2-methoxyphenoxy)benzoate (28): To the
crude aminoarene 27 in 120 ml of acetic acid and 65 ml of 15%
HCl was added dropwise 6.40 g (92.8 mmol) of NaNO2 in 15 ml
of H2O at 0°C. After additional stirring for 30 min, 160 ml of 30%
H3PO2 was added and stirring was continued for 12 h at 0°C. The
product was filtered off, washed (H2O), dried (P4O10), filtered
through an SiO2 pad (eluting with CH2Cl2) and recrystallized from
ethanol/H2O, 10:1; yield 16.9 g (74% from 26), colourless crystals,
m.p. 117°C. Ϫ IR (KBr): ν˜ ϭ 3060, 2985, 2945, 2830, 2735, 1715
and MS data were coincidental with those in ref.[7][17]
.
Methyl 4-(5-Formyl-2-methoxyphenoxy)-3-nitrobenzoate (25): To
a suspension of 4.80 g (0.20 mol) of NaH in 100 ml of DMF was
added dropwise 30.4 g (0.20 mol) of isovanilline (24) in 200 ml of
DMF. After stirring for 20 min at 20°C for hydrogen evolution,
43.1 g (0.20 mol) of methyl 4-chloro-3-nitrobenzoate (9) in 200 ml
of DMF was added dropwise with ice-cooling. The mixture was
allowed to warm up to 20°C and stirred for additional 2 h. After
evaporation of the solvent, the residue was taken up in 500 ml of
CHCl3, washed with each 300 ml of 2  NaOH, 2  HCl and H2O,
dried (MgSO4) and concentrated. The crude material was purified
by filtration through an SiO2 pad eluting with CHCl3 followed by
recrystallization from ethanol/chloroform, 1:2; yield 58.5 g (88%),
slightly yellow crystals, m.p. 114°C. Ϫ IR (KBr): ν˜ ϭ 3075, 3040,
3010, 2940, 2850 (COOCH3), 1685 (CHO), 1625, 1610, 1580, 1540
1
(COOCH3), 1695 (CHO), 1610, 1585 cmϪ1. Ϫ H NMR (CDCl3):
δ ϭ 9.86 (s, 1 H, CHO), 8.02Ϫ7.98 (m, 2 H, Ar-H), 7.75 (dd, J1 ϭ
8.4 Hz, J2 ϭ 2.0 Hz, 1 H, Ar-H), 7.59 (d, J ϭ 2.0 Hz, 1 H, Ar-H),
7.14 (d, J ϭ 8.4 Hz, 1 H, Ar-H), 6.95Ϫ6.92 (m, 2 H, Ar-H), 3.89
(s, 6 H, COOCH3, OCH3). Ϫ 13C NMR (CDCl3): δ ϭ 189.96
(CHO), 166.51 (COOCH3), 161.39, 156.80, 144.40, 131.69, 130.48,
129.07, 124.76, 121.92, 116.27, 112.55, 56.25 (OCH3), 51.96 (CO-
OCH3). Ϫ MS; m/z (%): 286 (92) [Mϩ], 255 (100) [Mϩ Ϫ OCH3],
240 (6), 212 (7), 183 (7), 155 (6), 149 (10), 127 (20), 119 (9), 92 (7),
79 (8), 76 (13), 63 (9), 59 (10), 50 (12). Ϫ C16H14O5 (286.3): calcd.
C 67.13, H 4.93; found C 67.56, H 4.98.
Methyl
4-[5-(1,3-Dioxolan-2-yl)-2-methoxyphenoxy]benzoate
(NO) cmϪ1. Ϫ 1H NMR (CDCl3): δ ϭ 9.89 (s, 1 H, CHO), 8.63 (29): 12.2 g (44.7 mmol) of the aldehyde 28 was dissolved in 250
(d, J ϭ 2.1 Hz, 1 H, Ar-H), 8.10 (dd, J1 ϭ 8.8 Hz, J2 ϭ 2.2 Hz, 1 ml of toluene together with 28.0 g (0.45 mol) of 1,2-dihydroxyeth-
H, Ar-H), 7.83 (dd, J1 ϭ 8.5 Hz, J2 ϭ 1.9 Hz, 1 H, Ar-H), 7.68 ane. 20.0 g of alumina (acidic, dried at 100°C in vacuo) was added
(d, J ϭ 1.9 Hz, 1 H, Ar-H, 7.18 (d, J ϭ 8.5 Hz, 1 H, Ar-H), 6.84
(d, J ϭ 8.8 Hz, 1 H, Ar-H), 3.94 (s, 3 H, COOCH3), 3.88 (s, 3 H,
OCH3). Ϫ 13C NMR (CDCl3): δ ϭ 189.66 (CHO), 164.66 (CO-
and the mixture refluxed for 24 h with vigorous stirring. After cool-
ing, the alumina was filtered off and washed several times with
CH2Cl2. The combined organic layers were washed (H2O), dried
OCH3), 156.28, 154.29, 143.11, 139.67, 134.98, 130.60, 130.18, (MgSO4) and concentrated. The crude dioxolane crystallized with
127.50, 124.94, 122.16, 117.49, 112.92, 56.42 (OCH3), 52.60 (CO-
ethanol and was recrystallized from ethanol/H2O, 5:1; yield 12.5 g
OCH3). Ϫ MS; m/z (%): 331 (13) [Mϩ], 300 (5) [Mϩ Ϫ OCH3], 284 (85%), colourless crystals, m.p. 74°C. Ϫ IR (KBr): ν˜ ϭ 2985, 2945,
(5), 225 (4), 180 (4), 151 (100) [ether cleavage], 139 (5), 119 (4), 95 2885, 1720 (CϭO), 1620, 1605, 1585 cmϪ1. Ϫ H NMR (CDCl3):
1
(53), 85 (41), 83 (64), 77 (23), 67 (9), 50 (10), 46 (18). Ϫ C16H13NO7 δ ϭ 7.97 (dd, J1 ϭ 7.0 Hz, J2 ϭ 2.0 Hz, 2 H, Ar-H), 7.32 (dd, J1 ϭ
Eur. J. Org. Chem. 1998, 877Ϫ888
883

T. Eicher, S. Fey, W. Puhl, E. Büchel, A. Speicher
FULL PAPER
8.4 Hz, J2 ϭ 2.0 Hz, 1 H, Ar-H), 7.21 (d, J ϭ 2.0 Hz, 1 H, Ar-H),
Methyl
3-Methoxy-4-[(trifluoromethylsulfonyl)oxy]benzoate
7.01 (d, J ϭ 8.4 Hz, 1 H, Ar-H), 6.91 (dd, J1 ϭ 7.0 Hz, J2
ϭ
(35): To 9.10 g (50.0 mmol) of methyl 4-hydroxy-3-methoxybenzo-
2.0 Hz, 2 H, Ar-H), 5.73 (s, 1 H, OCHO), 4.12Ϫ3.98 (m, 4 H, ate (methyl vanillinate, 33) and 6.00 g (75.8 mmol) of pyridine in
OCH2CH2O), 3.88 (s, 3 H, COOCH3), 3.79 (s, 3 H, OCH3). Ϫ 13C 150 ml of CH2Cl2 was added dropwise a solution of 15.0 g (53.2
NMR (CDCl3): δ ϭ 166.68 (COOCH3), 162.11, 152.41, 143.39, mmol) of trifluoromethanesulfonic anhydride in 20 ml of CH2Cl2
131.55, 131.36, 124.33, 124.07, 120.55, 115.92, 112.77, 103.13 at T < 0°C. Stirring was continued at 0°C for 30 min and the
(OCHO), 65.29 (OCH2CH2O), 56.04 (OCH3), 51.87 (COOCH3). Ϫ mixture poured into ice-cold water. The organic layer was washed
MS; m/z (%): 330 (78) [Mϩ], 299 (20) [Mϩ Ϫ OCH3], 285 (29), 258 with satd. NaHCO3, dried (MgSO4) and concentrated. The crude
(100) [Mϩ Ϫ dioxolane], 227 (25), 198 (6), 184 (8), 149 (29), 127 material was filtered through an SiO2 pad eluting with CH2Cl2;
(21), 119 (20), 92 (9), 76 (13), 73 (32) dioxolaneϩ], 59 (12), 44 (23).
yield 15.0 g (95%), colourless oil. Ϫ IR (film): ν˜ ϭ 3005, 2950,
1
Ϫ C18H18O6 (330.3): calcd. C 65.45, H 5.49; found C 65.75, H 5.35. 2840, 1735 (CϭO), 1610 cmϪ1. Ϫ H NMR (CDCl3): δ ϭ 7.72 (d,
J ϭ 1.9 Hz, 1 H, Ar-H), 7.67 (dd, J1 ϭ 8.4 Hz, J2 ϭ 1.9 Hz, 1 H,
{4-[5-(1,3-Dioxolan-2-yl)-2-methoxyphenoxy]phenyl}methanol
Ar-H), 7.28 (d, J ϭ 8.4 Hz, 1 H, Ar-H), 3.97 (s, 3 H, COOCH3),
(30): 11.5 g (34.8 mmol) of the methyl benzoate 29 was reduced
3.93 (s, 3 H, OCH3). Ϫ 13C NMR (CDCl3): δ ϭ 165.48 (COOCH3),
according to GP 2.2 (32.0 mmol of LiAlH4). The crude product
was recrystallized from ethanol/H2O, 2:1; yield 8.80 g (84%),
151.29, 141.71, 131.08, 122.37, 120.25, 117.07, 114.15, 56.32
(OCH3), 52.43 (COOCH3). Ϫ MS; m/z (%): 314 (81) [Mϩ], 283 (16)
colourless crystals, m.p. 80°C. Ϫ IR (KBr): ν ϭ 3460 (OH), 2965,
˜
[Mϩ Ϫ OCH3], 181 (100) [Mϩ Ϫ CF3SO2], 149 (11), 125 (8), 121
(9), 94 (4), 79 (6), 59 (4). Ϫ C10H9F3O6S (314.2): calcd. C 38.22, H
2.89; found C 38.37, H 2.74.
2885, 2800, 1625, 1610, 1590 cmϪ1. Ϫ 1H NMR (CDCl3): δ ϭ
7.26Ϫ7.23 (m, 3 H, Ar-H), 7.09 (d, J ϭ 2.0 Hz, 1 H, Ar-H), 6.98
(d, J ϭ 8.4 Hz, 1 H, Ar-H), 6.93Ϫ6.89 (m, 2 H, Ar-H), 5.68 (s, 1
H, OCHO), 4.58 (d, J ϭ 5.7 Hz, 2 H, CH2OH), 4.07Ϫ3.93 (m, 4
H, OCH2CH2O), 3.81 (s, 3 H, OCH3), 2.08 (s, 1 H, CH2OH). Ϫ
13C NMR (CDCl3): δ ϭ 157.35, 152.16, 144.92, 135.16, 131.01,
128.52, 123.15, 119.31, 117.25, 112.63, 103.24 (OCHO), 65.20
(OCH2CH2O), 64.82 (CH2OH), 56.11 (OCH3). Ϫ MS; m/z (%):
302 (100) [Mϩ], 257 (30), 243 (22), 230 (99) [Mϩ Ϫ dioxolane], 213
(9), 149 (15), 128 (13), 124 (20), 119 (25), 107 (23), 89 (31), 79 (37),
77 (57), 73 (59) dioxolaneϩ], 65 (19), 50 (25), 44 (56). Ϫ C17H18O5
(302.3): calcd. C 67.54, H 6.00; found C 67.23, H 6.05.
Methyl 3-Methoxy-4-(4-methoxy-2-methylphenyl)benzoate (36):
To 11.8 g (71.1 mmol) of the boronic acid 34 and 20.0 g (63.6
mmol) of the triflate 35 together with 2.30 g (2.00 mmol) of
Pd0(PPh3)4 in 350 ml of DMF was added 22.0 g (95.5 mmol) of
K3PO4 ·H2O and the mixture heated to 100°C for 2 h with vigorous
stirring. The batch was cooled to 20°C, poured into 300 ml of
diethyl ether, filtered and washed with H2O. The organic layer was
dried (MgSO4), concentrated and filtered through an alumina pad
(eluting with CH2Cl2) for removal of the remaining catalyst. The
crude product was recrystallized from methanol/H2O, 10:1; yield
16.9 g (93%), colourless crystals, m.p. 64°C. Ϫ IR (KBr): ν˜ ϭ 3000,
4-[5-(1,3-Dioxolan-2-yl)-2-methoxyphenoxy]benzaldehyde (31):
To a solution of 8.60 g (28.4 mmol) of benzyl alcohol 30 in 250 ml
of CH2Cl2 were added 25 ml of pyridine and 50.0 g (50 mmol) of
pyridinium chlorochromate (PCC) on alumina. The mixture was
stirred for 3 h at 20°C, filtered and the alumina washed several
times with diethyl ether. The combined organic layers were washed
(H2O), dried (MgSO4) and concentrated. The crude aldehyde was
filtered through an alumina pad eluting with diethyl ether; yield
7.30 g (86%), colourless unstable oil. Ϫ IR (film): ν˜ ϭ 3060, 2955,
2885, 2835, 2735, 1700 (CHO), 1605, 1585 cmϪ1. Ϫ 1H NMR
(CDCl3): δ ϭ 9.89 (s, 1 H; CHO), 7.82Ϫ7.79 (m, 2 H, Ar-H), 7.35
(dd, J1 ϭ 8.4 Hz, J2 ϭ 2.1 Hz, 1 H, Ar-H), 7.24 (d, J ϭ 2.1 Hz, 1
H, Ar-H), 7.03 (d, J ϭ 8.4 Hz, 1 H, Ar-H), 7.00Ϫ6.97 (m, 2 H,
Ar-H), 5.74 (s, 1 H, OCHO), 4.13Ϫ4.00 (m, 4 H, OCH2CH2O),
3.79 (s, 3 H, OCH3). Ϫ 13C NMR (CDCl3): δ ϭ 190.71 (CHO),
163.41, 152.41, 142.92, 131.84, 131.46, 131.08, 124.73, 120.80,
116.34, 112.81, 103.07 (OCHO), 65.31 (OCH2CH2O), 56.04
(OCH3).
1
2945, 2830, 1725 (CϭO), 1610, 1565 cmϪ1. Ϫ H NMR (CDCl3):
δ ϭ 7.69 (dd, J1 ϭ 7.8 Hz, J2 ϭ 1.3 Hz, 1 H, Ar-H), 7.62 (s, 1 H,
Ar-H), 7.19 (d, J ϭ 7.8 Hz, 1 H, Ar-H), 7.08 (d, J ϭ 8.3 Hz, 1 H,
Ar-H), 6.82Ϫ6.77 (m, 2 H, Ar-H), 3.94 (s, 3 H, COOCH3), 3.82 (s,
6 H, OCH3), 2.10 (s, 3 H, CH3). Ϫ 13C NMR (CDCl3): δ ϭ 167.06
(COOCH3), 159.15, 156.88, 138.02, 135.65, 131.35, 130.72, 130.31,
130.13, 121.96, 115.34, 111.44, 110.93, 55.63, 55.17 (OCH3), 52.17
(COOCH3), 20.14 (CH3). Ϫ MS; m/z (%): 286 (100) [Mϩ], 255 (15)
[Mϩ Ϫ OCH3], 239 (7), 212 (22), 197 (10), 169 (5), 152 (7), 141 (8),
128 (9), 115 (7), 104 (3), 92 (4), 59 (9). Ϫ C17H18O4 (286.3): calcd.
C 71.31, H 6.34; found C 71.05, H 6.60.
{5-Methoxy-2-[2-methoxy-4-(methoxycarbonyl)phenyl]-
benzyl}triphenylphosphonium Bromide (37): From 8.00 g (27.9
mmol) of the methylarene 36 the crude benzyl bromide was ob-
tained according to GP 2.1 and the corresponding phosphonium
salt using GP 2.3 (acetonitrile, reflux 2 h). After evaporation of the
4-Methoxy-2-methylphenylboronic Acid (34): To a solution of solvent, the phosphonium salt precipitated on digesting with hot
80.6 g (0.35 mol) of tributyl borate in 150 ml of THF and 150 ml toluene; yield 11.4 g (68%), colourless crystals, m.p. 212°C. Ϫ IR
of diethyl ether was added at T < Ϫ60°C a Grignard solution,pre-
(KBr): ν˜ ϭ 3040, 3000, 2950, 2830, 1720 (CϭO), 1610, 1570, 1545
pared from 70.4 g (0.35 mol) of 1-bromo-4-methoxy-2-methylben- cmϪ1. Ϫ 1H NMR (CDCl3): δ ϭ 7.79Ϫ7.75 (m, 3 H, Ar-H),
zene (32) and 8.50 g (0.35 mol) of Mg in 250 ml of THF. The 7.57Ϫ7.54 (m, 7 H, Ar-H), 7.39Ϫ7.34 (m, 7 H, Ar-H), 7.00 (d, J ϭ
mixture was allowed to warm up to 20°C within about 12 h and 8.4 Hz, 1 H, Ar-H), 6.92Ϫ6.86 (m, 2 H, Ar-H), 6.35 (d, J ϭ 7.7
hydrolysed by adding dropwise 300 ml of 10% HCl. Stirring was Hz, 1 H, Ar-H), 5.42 and 4.60 (t, J( 31P-1H) ϭ 14.3 Hz, each 1 H,
continued for 30 min and the mixture extracted three times with CH2P), 3.97 (s, 3 H; COOCH3), 3.74 and 3.54 (s, each 3 H, OCH3).
diethyl ether. The combined organic layers were extracted three
times with 1  NaOH and the alkaline solution acidified with
Ϫ
13C NMR (CDCl3): δ ϭ 166.62 (COOCH3), 159.44, 156.13,
134.99, 134.28, 134.18, 133.23, 132.41, 131.11, 131.03, 130.85,
concd. HCl. The product precipitated and was filtered off and 130.28, 130.14, 127.59, 127.51, 123.96, 122.22, 118.06, 117.22,
dried; yield 43.3 g (75%); colourless crystals, m.p 191°C. Ϫ IR 116.43, 115.85, 111.91, 56.10, 55.82 (OCH3), 29.73, 29.26 (CH2P).
1
(KBr): ν˜ ϭ 3300 (OH), 3000, 2960, 2930, 1565 cmϪ1. Ϫ H NMR Ϫ MS; m/z (%): 531 (45) [Mϩ Ϫ Br Ϫ CH3], 515 (13) [Mϩ Ϫ Br
([D6]DMSO): δ ϭ 7.73 (s, 2 H, OH), 7.45 (dd, J1 ϭ 5.0 Hz, J2 ϭ Ϫ OCH3], 445 (26), 370 (7), 284 (22) [Mϩ Ϫ Br Ϫ PPh3], 269 (73),
3.9 Hz, 1 H, Ar-H), 6.69Ϫ6.67 (m, 2 H, Ar-H), 3.72 (s, 3 H, 262 (100) [PPh3ϩ], 239 (33), 183 (38), 139 (13), 108 (11). Ϫ
OCH3), 2.41 (s, 3 H, CH3). Ϫ 13C NMR ([D6]DMSO): δ ϭ 159.97, C35H32BrO4P (627.5): calcd. C 66.99, H 5.14; found C 67.11, H
143.97, 135.42, 115.00, 109.79, 54.65 (OCH3), 22.32 (CH3).
5.15.
884
Eur. J. Org. Chem. 1998, 877Ϫ888

Bryophyte Constituents, 9
FULL PAPER
Methyl
phenoxy]phenyl}-1-ethenyl]-4-methoxyphenyl}-3-methoxybenzoate (19), 227 (15), 213 (11), 196 (6), 152 (5), 91 (9), 73 (11) dioxolaneϩ],
(38): Reaction between 7.30 g (24.3 mmol) of the aldehyde 31 and
57 (15), 42 (43), 31 (90) [OCH3ϩ]. Ϫ C33H34O7 (542.6): calcd. C
4-{2-[(E/Z)-2-{4-[5-(1,3-Dioxolan-2-yl)-2-methoxy- 542 (24) [Mϩ], 526 (4), 285 (100) benzyl cleavage], 258 (18), 241
16.8 g (26.8 mmol) of the phosphonium salt 37 according to GP 73.04, H 6.32; found C 73.00, H 6.45.
3.1, followed by filtration through an Al2O3 pad (eluent: CH2Cl2)
4-Methoxy-3-[4-(5-methoxy-2-{2-methoxy-4-[(1,1,1-triphenyl-
resulted in a yellow oil which was purified by CC (Al2O3; diethyl
ether/petroleum ether, 3:1); yield 11.8 g (85%), colourless viscous
oil. Ϫ IR (film): ν˜ ϭ 2990, 2945, 2885, 2830, 1725 (CϭO), 1605,
1565 cmϪ1. Ϫ 1H NMR (CDCl3): δ ϭ 7.71Ϫ6.17 (m, 15 H, Ar-H,
CHϭCH), 5.70 and 5.69 (s, 1 H, OCHO), 4.08Ϫ3.96 (m, 4 H,
OCH2CH2O), 3.94Ϫ3.81 (s not resolved, 12 H, COOCH3, OCH3).
phosphonio)methyl]phenyl}phenethyl)phenoxy]benzaldehyde Bro-
mide (41): Gaseous HBr was passed with vigorous stirring into a
solution of 9.20 g (17.0 mmol) of benzyl alcohol 40 in 300 ml of
CHCl3 for 15 min at 20°C and stirring was continued for 2 h. The
solution was washed with satd. NaHCO3, followed by H2O and
dried (MgSO4). From the crude benzyl bromide obtained after
evaporation of the solvent the phosphonium salt was prepared ac-
cording to GP 2.3 (toluene); yield 10.8 g (77%), colourless crystals,
m.p. 209°C. Ϫ IR (KBr): ν˜ ϭ 3045, 2995, 2950, 2890, 2775, 1690
Ϫ
13C NMR (CDCl3): δ ϭ 167.00 (COOCH3), 159.40, 158.85,
157.61, 157.00, 156.88, 152.24, 144.84, 144.64, 138.20, 137.25,
135.07, 134.69, 132.01, 131.58, 131.41, 131.26, 131.12, 130.57,
130.25, 129.76, 129.50, 129.35, 128,78, 127,71, 126.03, 123.83,
123.32, 123.12, 121.93, 121.79, 119.62, 119.35, 117.18, 116.79,
114.02, 113.47, 113.15, 112.84, 111.79, 109.89, 103.23 (OCHO),
65.23 (OCH2CH2O), 56.12, 55.81, 55.46, 55.34, 55.18 (OCH3),
53.40, 52.14 (COOCH3). Ϫ MS; m/z (%): 569 (100) [Mϩ], 524 (12),
496 (5) [Mϩ Ϫ dioxolane], 466 (3), 340 (11), 315 (7), 285 (17), 253
(8), 239 (8), 145 (5), 73 (17) dioxolaneϩ], 59 (12), 44 (17), 42 (20).
Ϫ C34H32O8 (568.6): calcd. C 71.82, H 5.67; found C 71.38, H 5.89.
1
(CHO), 1605, 1575 cmϪ1. Ϫ H NMR (CDCl3): δ ϭ 9.75 (s, 1 H,
CHO), 7.78Ϫ7.70 (m, 10 H, Ar-H), 7.63 (dd, J1 ϭ 8.4 Hz, J2
ϭ
1.9 Hz, 1 H, Ar-H), 7.57Ϫ7.52 (m, 6 H, Ar-H), 7.31 (d, J ϭ 1.9
Hz, 1 H, Ar-H), 7.12 (d, J ϭ 8.4 Hz, 1 H, Ar-H), 6.98Ϫ6.90 (m, 3
H, Ar-H), 6.85Ϫ6.70 (m, 6 H, Ar-H), 5.42 (br. s, 2 H, CH2P), 3.92,
3.79, 3.40 (s, each 3 H, OCH3), 2.68 (br. s, 4 H, ArCH2CH2Ar). Ϫ
13C NMR (CDCl3): δ ϭ 190.22 (CHO), 159.14, 157.01, 156.41,
155.06, 146.75, 141.23, 137.13, 134.97, 134.61, 134.53, 131.57,
131.29, 130.30, 130.17, 130.05, 129.56, 129.05, 128.35, 127.74,
127.65, 123.95, 123.02, 122.98, 118.85, 118.47, 118.05, 117.63,
114.92, 114.42, 112.40, 111.27, 56.43, 55.90, 55.26 (OCH3), 36.08,
35.48 (ArCH2CH2Ar), 31.02, 30.56 (CH2P). Ϫ MS; m/z (%): 557
(100), 524 (8), 479 (26), 463 (15), 445 (4), (13), 329 (4), 279 (25),
263 (26), 262 (39) [PPh3ϩ]. Ϫ C49H44BrO5P (823.8): calcd. C 71.44,
H 5.38; found C 71.27, H 5.23.
Methyl
4-(2-{4-[5-(1,3-Dioxolan-2-yl)-2-methoxyphenoxy]-
phenetyl}-4-methoxyphenyl)-3-methoxybenzoate (39): 11.8 g (20.8
mmol) of the (E/Z)-stilbene 38 was hydrogenated according to GP
1 (5% Pd/C, ethyl acetate, 5 bar, 18 h) in presence of 30 ml of
triethylamine. Filtering through an Al2O3 pad (eluent: CH2Cl2)
yielded 11.0 g (93%) of a colourless oil. Ϫ IR (film): ν˜ ϭ 2990,
1
2975, 2830, 1720 (CϭO), 1610, 1570 cmϪ1. Ϫ H NMR (CDCl3):
δ ϭ 7.68 (dd, J1 ϭ 7.7 Hz, J2 ϭ 1.6 Hz, 1 H, Ar-H), 7.62 (d, J ϭ
1.4 Hz, 1 H, Ar-H), 7.22 (dd, J1 ϭ 8.4 Hz, J2 ϭ 2.0 Hz, 1 H, Ar-
H), 7.13 (d, J ϭ 7.7 Hz, 1 H, Ar-H), 7.07 (s, 1 H, Ar-H), 7.05 (d,
J ϭ 1.6 Hz, 1 H, Ar-H), 6.97 (d, J ϭ 8.4 Hz, 1 H, Ar-H), 6.84Ϫ6.76
(m, 6 H, Ar-H), 5.68 (s, 1 H, OCHO), 4.07Ϫ3.95 (m, 4 H, OCH2-
CH2O), 3.94 (s, 3 H, COOCH3), 3.82, 3.81, 3.80 (s, each 3 H,
OCH3), 2.65 (br. s, 4 H, ArCH2CH2Ar). Ϫ 13C NMR (CDCl3): δ ϭ
166.98 (COOCH3), 159.20, 156.86, 155.87, 152.09, 145.22, 141.46,
135.92, 135.45, 131.55, 130.95, 130.40, 129.85, 129.30, 122.77,
121.91, 119.08, 117.13, 114.56, 112.52, 111.42, 111.22, 103.25
(OCHO), 65.19 (OCH2CH2O), 56.10, 55.64, 55.17 (OCH3), 52.14
(COOCH3), 36.30, 35.85 (ArCH2CH2Ar). Ϫ MS; m/z (%): 570 (20)
[Mϩ], 285 (100) benzyl cleavage], 241 (21), 213 (21), 205 (9), 167
(8), 149 (30), 91 (18), 83 (16), 73 (23) dioxolaneϩ], 71 (26), 69 (15),
57 (35), 55 (24), 42 (58). Ϫ C34H34O8 (570.6): calcd. C 71.56, H
6.01; found C 71.08, H 6.18.
Trimethyl Ether of (E/Z)-Dehydroriccardin C (42): 3.00 g (3.64
mmol) of the phosphonium salt 41 was subjected to a Wittig cycli-
zation according to GP 3.2. The residue was purified by CC (SiO2;
diethyl ether/petroleum ether, 2:1); yield 1.35 g (80%), colourless
crystals, m.p. 166Ϫ170°C (ethanol/CHCl3, 3:1). Ϫ IR (KBr): ν˜ ϭ
3000, 2930, 2825, 1610, 1570, 1550 cmϪ1. Ϫ 1H NMR (CDCl3):
δ ϭ 7.36Ϫ6.15 (m, 15 H, Ar-H, CHϭCH), 3.96Ϫ3.64 (s, not re-
solved, 9 H, OCH3), 3.13Ϫ2.59 (m, 4 H, ArCH2CH2Ar). Ϫ 13C
NMR (CDCl3): δ ϭ 159.28, 159.11, 158.53, 155.78, 154.52, 152.48,
148.80, 148.39, 147.58, 142.80, 141.20, 139.32, 136.70, 135.91,
134.41, 132.53, 131.87, 131.50, 130.97, 130.85, 129.88, 129.68,
129.19, 129.01, 128.76, 128.49, 127.88, 124.05, 123.87, 123.65,
122.74, 122.46, 122.07, 121.73, 120.41, 119.59, 115.46, 113.59,
111.82, 111.59, 111.35, 110.86, 110.40, 56.30, 56.00, 55.75, 55.23,
55.16 (OCH3), 36.54, 35.81, 35.33, 34.15 (ArCH2CH2Ar). Ϫ MS;
m/z (%): 464 (100) [Mϩ], 449 (3), 358 (6), 343 (3), 311 (3), 232 (6),
216 (5), 152 (3), 107 (2), 91 (3), 77 (3), 43 (4). Ϫ C31H28O4 (464.6):
calcd. C 80.15, H 6.08; found C 79.95, H 6.40.
[4-(2-{4-[5-(1,3-Dioxolan-2-yl)-2-methoxyphenoxy]phenethyl}-
4-methoxyphenyl)-3-methoxyphenyl]methanol (40): 11.0 g (19.3
mmol) of the methyl benzoate 39 was reduced according to GP 2.2
(18.0 mmol of LiAlH4). The crude product was purified by fil-
Trimethyl Ether of Riccardin C (43): 1.30 g (2.80 mmol) of the
tration through an Al2O3 pad (eluent: diethyl ether); yield 9.20 g (E/Z)-stilbene 42 was hydrogenated according to GP 1 (5% Pd/C,
(88%), colourless oil. IR (film): ν˜ ϭ 3470 (OH), 2990, 2930, 2885, ethyl acetate, 5 bar, 15 h). Purification (CC: SiO2; CH2Cl2) resulted
1
2830, 1610, 1575 cmϪ1. Ϫ H NMR (CDCl3): δ ϭ 7.22 (dd, J1 ϭ in a viscous oil which crystallized on heating with ethanol; yield
8.4 Hz, J2 ϭ 2.0 Hz, 1 H, Ar-H), 7.07Ϫ7.04 (m, 3 H, Ar-H), 6.96 1.20 g (92%), colourless crystals, m.p. 155°C. Ϫ IR (KBr): ν˜ ϭ
(d, J ϭ 8.6 Hz, 1 H, Ar-H), 6.93 (s, 1 H, Ar-H), 6.85 (d, J ϭ 8.6 3020, 3000, 2925, 2850, 2825, 1610, 1585, 1575 cmϪ1. Ϫ UV (etha-
Hz, 1 H, Ar-H), 6.81Ϫ6.76 (m, 6 H, Ar-H), 5.67 (s, 1 H, OCHO),
4.71 (d, J ϭ 5.5 Hz, 2 H, CH2OH), 4.07Ϫ3.93 (m, 4 H, OCH2-
nol): λmax (log ε) ϭ 280 (3.73), 220 (4.10) nm. Ϫ 1H NMR (CDCl3):
δ ϭ 7.05 (d, J ϭ 8.5 Hz, 1 H, Ar-H), 6.96 (d, J ϭ 2.7 Hz, 1 H,
CH2O), 3.81, 3.80, 3.75 (s, each 3 H, OCH3), 2.67 (br. s, 4 H, Ar-H), 6.87 (d, J ϭ 8.2 Hz, 1 H, Ar-H), 6.83Ϫ6.68 (m, 7 H, Ar-
ArCH2CH2Ar), 2.01 (t, J ϭ 5.5 Hz, 1 H, CH2OH). Ϫ 13C NMR H), 6.43 (d, J ϭ 1.3 Hz, 1 H, Ar-H), 6.23 (dd, J1 ϭ 7.6 Hz, J2 ϭ
(CDCl3): δ ϭ 158.88, 157.06, 155.78, 152.11, 145.27, 141.72,
1.4 Hz, 1 H, Ar-H), 5.36 (d, J ϭ 2.0 Hz, 1 H, Ar-H), 3.93, 3.87,
141.60, 136.23, 131.64, 131.32, 130.87, 130.57, 129.64, 129.33,
3.66 (s, each 3 H, OCH3), 3.07, 2.92, 2.84, 2.62 (each mc, total 8 H,
122,77, 119.07, 118.75, 117.11, 114.43, 112.52, 111.11, 109.28, ArCH2CH2Ar). Ϫ 13C NMR (CDCl3): δ ϭ 159.20, 156.07, 152.88,
103.27 (O-CH-O), 65.31 (CH2OH), 65.19 (OCH2CH2O), 56.11,
148.80, 147.03, 143.28, 141.23, 139.73, 133.89, 132.47, 132.43,
55.46, 55.16 (OCH3), 36.25, 35.82 (ArCH2CH2Ar). Ϫ MS; m/z (%): 130.97, 129.37, 127.70, 123.84, 122.29, 121.70, 121.45, 116.79,
Eur. J. Org. Chem. 1998, 877Ϫ888
885

T. Eicher, S. Fey, W. Puhl, E. Büchel, A. Speicher
FULL PAPER
115.41, 112.07, 111.48, 111.30, 56.18 (OCH3), 55.23 (OCH3), 38.25, NMR ([D6]DMSO): δ ϭ 191.4, 167.8, 136.9, 133.6, 129.1, 110.7,
38.08, 37.21, 35.64 (ArCH2CH2Ar). Ϫ MS; m/z (%): 466 (95) [Mϩ], 55.8.
239 (100) benzyl cleavage], 233 (14), 227 (10), 225 (12), 211 (14),
209 (7), 165 (5), 153 (4), 121 (4), 105 (12), 90 (21), 77 (8). Ϫ
C31H30O4 (466.6): calcd. C 79.80, H 6.48; found C 79.70, H 6.65.
3-[5-(1,3-Dioxan-2-yl)-2-methoxyphenyl]-4-methoxybenz-
aldehyde (47): 4.00 g (22.2 mmol) of the boronic acid 46 in 20 ml
of ethanol was added to a mixture of 5.46 g (20.0 mmol) of bromo-
Riccardin C (4): 1.00 g (2.14 mmol) of the trimethyl ether 43 was
cleaved according to GP 4 (20.0 mmol of BBr3, 0°C Ǟ 20°C). 20 ml of 2  aq. Na2CO3. After heating to reflux for 24 h the
arene 45, 40 ml of toluene, 0.70 g (0.61 mmol) of Pd0(PPh3)4 and
The crude product was isolated by extraction with CH2Cl2 and
purification by CC (SiO2; diethyl ether) resulting in a foam which
crystallized on heating with n-hexane; yield 0.80 g (88%), colourless
mixture was cooled and water was added followed by extraction
with diethyl ether. The combined organic layers were dried
(MgSO4) and concentrated. The crude biphenyl was purified by CC
crystals, m.p. 194°C. Ϫ IR (KBr): ν˜ ϭ 3600, 3400 (OH), 3015, (alumina; CH2Cl2); yield 5.65 g (86%), colourless oil, solidifying,
2960, 2915, 2845, 1605, 1580, 1565, 1505, 1435, 1340, 1275, 1225,
m.p. 105°C. Ϫ IR (film): ν˜ ϭ 2965, 2840, 2725, 1690 (CϭO), 1605
1190, 1160, 1105, 1015, 975, 930, 900, 850, 810, 720 cmϪ1. Ϫ UV cmϪ1. Ϫ 1H NMR (CDCl3): δ ϭ 9.89 (s, 1 H, CHO), 7.86 (dd,
(ethanol): λmax (log ε) ϭ 280 (3.90), 225 (4.14) nm. Ϫ 1H NMR J1 ϭ 8.8 Hz, J2 ϭ 2.2 Hz, 1 H, Ar-H), 7.76 (d, J ϭ 2.2 Hz, 1 H,
(CDCl3 / [D6]DMSO): δ ϭ 8.48 (s, 1 H, OH), 6.98 (d, J ϭ 8.4 Hz,
Ar-H), 7.47 (dd, J1 ϭ 8.4 Hz, J2 ϭ 2.2 Hz, 1 H, Ar-H), 7.35 (d,
1 H, Ar-H), 6.94 (d, J ϭ 2.5 Hz, 1 H, Ar-H), 6.88 (d, J ϭ 8.0 Hz, J ϭ 2.2 Hz, 1 H, Ar-H), 7.03 (d, J ϭ 8.4 Hz, 1 H, Ar-H), 6.95 (d,
1 H, Ar-H), 6.79 (d, J ϭ 2.5 Hz, 1 H, Ar-H), 6.78Ϫ6.68 (m, 6 H, J ϭ 8.8 Hz, 1 H, Ar-H), 5.49 (s, 1 H, OCHO), 4.25Ϫ4.22 and
Ar-H), 6.70 (s, 1 H, OH), 6.36 (d, J ϭ 1.3 Hz, 1 H, Ar-H), 6.24 (s, 4.00Ϫ3.93 (m, each 2 H, OCH2), 3.81 (s, 3 H, OCH3), 3.75 (s, 3 H,
1 H, OH), 6.16 (dd, J1 ϭ 7.6 Hz, J2 ϭ 1.3 Hz, 1 H, Ar-H), 5.34
(d, J ϭ 1.8 Hz, 1 H, Ar-H), 3.00, 2.88, 2.62 (each br. s, total 8
H, ArCH2CH2Ar). Ϫ 13C NMR (CDCl3/[D6]DMSO): δ ϭ 157.09,
152.78, 152.58, 146.72, 143.65, 143.38, 141.34, 139.98, 133.02,
OCH3), 2.26Ϫ2.14 and 1.44Ϫ1.40 (m, each 1 H, HCH). Ϫ 13C
NMR (CDCl3): δ ϭ 190.9. 162.3, 157.5, 133.5, 131.2, 131.1, 129.6,
129.1, 128.7, 127.0, 126.4, 110.8, 101.5, 67.4, 55.9, 25.8. Ϫ MS; m/z
(%): 328 (31) [Mϩ], 270 (100), 92 (11), 87 (18), 77 (30), 65 (12), 63
132.53, 131.67, 129.33, 127.94, 125.22, 122.25, 122.02, 121.08, (15), 57 (23), 55 (12), 51 (14), 45 (18). Ϫ C19H20O5 (328.4): calcd.
117.40, 116.47, 116.10, 115.30, 114.19, 38.13, 37.76, 37.03, 35.07. C 69.50, H 6.14; found C 69.10, H 6.14.
Ϫ MS; m/z (%): 424 (88) [Mϩ], 225 (7), 212 (40), 211 (100) benzyl
Methyl 4-{2-[(E/Z)-2-{3-[5-(1,3-Dioxan-2-yl)-2-methoxyphen-
yl]-4-methoxyphenyl}-1-ethenyl]-4-methoxyphenyl}-3-methoxy-
benzoate (48): Reaction between 5.00 g (15.2 mmol) of the aldehyde
47 and 10.5 g (16.7 mmol) of the phosphonium bromide 37 accord-
cleavage], 197 (9), 152 (4), 120 (7), 107 (24), 91 (19), 77 (10), 55 (5),
1
31 (12). The H-NMR and MS data were coincidental with those
reported in ref.[18]
.
2-(3-Bromo-4-methoxyphenyl)-1,3-dioxane (45): 4.30
g
(20.0
ing to GP 3.1, followed by filtration through an Al2O3 pad (CH2Cl2
mmol) of 3-bromo-4-methoxybenzaldehyde (44) and 1.60 ml (1.67 as eluent) yielded 8.00 g (88%), colourless viscous oil. Ϫ IR (KBr):
g, 22.0 mmol) of 1,3-propanediol together with 0.10 g of toluene-
4-sulfonic acid in 50 ml of toluene were heated to reflux for 24 h
ν˜ ϭ 2945, 2830, 1720 (CϭO), 1600 cmϪ1. Ϫ 1H NMR (CDCl3):
δ ϭ 7.69Ϫ7.15 (m, 9 H, Ar-H), 6.97 (d, J ϭ 16.2 Hz, 1 H, E-CHϭ
in a Dean-Stark water separator. After cooling, the toluene layer CH), 6.95Ϫ6.73 (m, 3 H, Ar-H), 6.69 (d, J ϭ 16.2 Hz, 1 H, E-
was washed (1  NaOH, satd. NaCl), dried (MgSO4) and concen- CHϭCH), 6.34 (d, J ϭ 12.2 Hz, 1 H, Z-CHϭCH), 6.15 (d, J ϭ
trated. The crude dioxane was purified by CC (SiO2; ethyl acetate/
hexane, 1:1) or distillation; yield 5.30 g (97%), colourless oil, soli-
12.2 Hz, 1 H, Z-CHϭCH), 5.46 (s, 1 H, OCHO, E), 5.45 (s, 1 H,
OCHO, Z), 4.23Ϫ4.19 and 3.97Ϫ3.94 (m, each 2 H, OCH2), 3.93,
difying; m.p. 66°C, b.p.0.001 116°C. Ϫ IR (film): ν˜ ϭ 2955, 2840 3.88, 3.78, 3.72, 3.70 (s, each 3 H, OCH3), 2.22Ϫ2.12 and
1
(OCϪH), 1610 cmϪ1. Ϫ H NMR (CDCl3): δ ϭ 7.67 (d, J ϭ 1.8 1.40Ϫ1.37 (m, each 1 H, HCH). Ϫ 13C NMR (CDCl3): δ ϭ 167.1,
Hz, 1 H), 7.37 (dd, J1 ϭ 8.4 Hz, J2 ϭ 2.2 Hz, 1 H), 6.86 (d, J ϭ
159.5, 157.1, 156.9, 137.6, 134.9, 132.1, 131.7, 131.4, 131.1, 130.6,
8.4 Hz, 1 H), 5.42 (s, 1 H, OCHO), 4.26Ϫ4.21 and 3.98Ϫ3.92 (m, 130.2, 130.0, 129.8, 129.4, 129.3, 128.0, 127.6, 126.7, 126.4, 125.5,
each 2 H, OCH2), 3.87 (s, 3 H, OCH3), 2.25Ϫ2.13 and 1.45Ϫ1.40
(m , each 1 H, HCH). Ϫ 13C NMR (CDCl3): δ ϭ 156.1, 132.7,
122.0, 113.1, 111.9, 111.5, 110.8, 110.1, 101.7, 67.4, 55.9, 55.4, 52.2,
27.0. Ϫ MS; m/z (%): 597 (4) [Mϩ], 539 (18), 387 (100), 327 (49),
131.2, 126,3, 111.5, 100.5, 67.3, 56.3, 25.7. Ϫ MS; m/z (%): 273 (13) 299 (15), 269 (26), 195 (11), 193 (29), 134 (11), 87 (28), 59 (11), 57
[Mϩ], 243 (18), 241 (11), 193 (90), 188 (24), 186 (19), 163 (13), 157 (15). Ϫ C36H36O8 (596.6): calcd. C 72.46, H 6.08; found C 72.22,
(12), 155 (17), 134 (22), 120 (14), 118 (12), 107 (25), 104 (32), 103
(16), 86 (27), 82 (17), 78 (14), 69 (22), 65 (41), 55 (41), 43 (100). Ϫ
C11H13BrO3 (273.1): calcd. C 48.37, H 4.80; found C 49.02, H 4.90.
H 5.98.
Methyl 4-(2-{3-[5-(1,3-Dioxan-2-yl)-2-methoxyphenyl]-4-meth-
oxyphenetyl}-4-methoxyphenyl)-3-methoxybenzoate (49): 8.00
g
5-Formyl-2-methoxyphenylboronic Acid (46): To 1.10 g (4.02 (13.4 mmol) of the (E/Z)-stilbene 48 was hydrogenated according
mmol) of the bromoarene 45 in 15 ml of diethyl ether was added to GP 1 (2.5 g 5%, Pd/C ethyl acetate, 3.5 bar, 24 h) in the presence
1.80 ml (4.50 mmol) of 2.5  nBuLi in hexane at T < Ϫ70°C. After of 25 ml of triethylamine. Filtering through an Al2O3 pad (eluting
stirring for additional 4 h at Ϫ70°C, 1.40 ml (1.16 g, 5.04 mmol) with CH2Cl2) yielded 7.50 g (93%) of a colourless oil. Ϫ IR (KBr):
of tributyl borate was added and the mixture was allowed to warm ν˜ ϭ 2935, 2830, 1720 (CϭO), 1610, 1570 cmϪ1. Ϫ 1H NMR
up to 20°C within about 12 h and hydrolysed by adding 8 ml of 2 (CDCl3): δ ϭ 7.66 (dd, J1 ϭ 7.5 Hz, J2 ϭ 1.3 Hz, 1 H, Ar-H), 7.61
 HCl. The product precipitated and was filtered off. A second
fraction could be obtained by extracting the ethereal layer with 2
 NaOH and acidifying. The combined boronic acid was recrys-
tallized from water and dried in vacuo (extensive drying over P4O10
(d, J ϭ 1.3 Hz, 1 H, Ar-H), 7.42 (dd, J1 ϭ 8.4 Hz, J2 ϭ 2.2 Hz, 1
H, Ar-H), 7.24 (d, J ϭ 2.2 Hz, 1 H, Ar-H), 7.15 (d, J ϭ 7.5 Hz, 1
H, Ar-H), 7.05 (d, J ϭ 8.4 Hz, 1 H, Ar-H), 6.91 (d, J ϭ 8.8 Hz, 1
H, Ar-H), 6.86 (d, J ϭ 2.2 Hz, 1 H, Ar-H), 6.83Ϫ6.78 (m, 3 H,
may result in formation of the anhydride); yield 0.54 g (75%), Ar-H), 6.75 (d, J ϭ 8.4 Hz, 1 H, Ar-H), 5.47 (s, 1 H, OCHO),
colourless crystals, m.p. 160°C. Ϫ IR (KBr): ν˜ ϭ 3235 (OH), 1685 4.26Ϫ4.22 and 4.00Ϫ3.96 (m, each 2 H, OCH2), 3.93, 3.80, 3.79,
(CϭO), 1660, 1600, 1575 cmϪ1. Ϫ 1H NMR ([D6]DMSO): δ ϭ 3.72, 3.67 (s, each 3 H, OCH3), 2.67 (br. s, 4 H, CH2CH2),
9.88 (s, 1 H, CHO), 8.06 (d, J ϭ 2.0 Hz, 1 H), 7.93 [m, 3 H, Ar-
2.26Ϫ2.14 and 1.43Ϫ1.39 (m, each 1 H, HCH). Ϫ 13C NMR
(CDCl3): δ ϭ 167.0, 159.3, 157.5, 156.9, 155.5, 141.8, 135.6, 133.5,
H, B(OH)2], 7.17 (d, J ϭ 8.6 Hz, 1 H), 3.90 (s, 3 H, OCH3). Ϫ 13C
886
Eur. J. Org. Chem. 1998, 877Ϫ888

Bryophyte Constituents, 9
131.6, 131.4, 131.0, 130.9, 130.4, 129.9, 129.3, 128.1, 127.9, 127.7, 132.1, 131.4, 131.2, 131.0, 130.3, 129.6, 128.9, 127.2, 127.0, 120.8,
FULL PAPER
126.2, 122.0, 114.4, 111.5, 111.4, 111.2, 110.8, 101.7, 67.3, 55.8,
114.2, 113.9, 111.5, 111.0, 110.8, 110.6, 110.4, 55.8, 55.6, 55.5, 55.1,
55.7, 55.2, 52.1, 36.2, 35.8, 25.9. Ϫ MS; m/z (%): 599 (100) [Mϩ], 37.9, 37.6. Ϫ MS; m/z (%): 478 (97) [Mϩ], 302 (19), 300 (24), 288
313 (35), 290 (10), 117 (19), 89 (82). Ϫ C36H38O8 (598.7): calcd. C (36), 286 (41), 268 (35), 266 (28), 254 (59), 252 (55), 239 (18), 167
72.22, H 6.40; found C 71.86, H 6.40.
(16), 149 (26), 97 (12), 85 (68), 83 (100), 71 (21), 69 (16), 57 (33),
55 (16), 49 (11), 47 (26). Ϫ C32H30O4 (478.6): calcd. C 80.31, H
6.32; found C 80.12, H 6.42.
3-(5-{2-[4-(Hydroxymethyl)-2-methoxyphenyl]-5-methoxy-
phenethyl}-2-methoxyphenyl)-4-methoxybenzaldehyde (50): 5.00 g
(8.35 mmol) of the methyl benzoate 49 was reduced according to
GP 2.2 (8.00 mmol of LiAlH4). The crude benzyl alcohol still bear-
Isoplagiochin C (5): 480 mg (1.00 mmol) of the tetramethyl ether
52 was cleaved according to GP 4 (8.00 mmol BBr3, Ϫ78°C Ǟ
ing a dioxane moiety was stirred in 40 ml of acetic acid/10 ml of 20°C). The crude product was isolated by extraction with CH2Cl2
H2O for 2 h at 20°C. 300 ml of an ice-cold satd. Na2CO3 solution and purified by flash chromatography on RP-18 using methanol/
was added, followed by 250 ml of a satd. NaCl solution. The mix- H2O, 1:1; yield 363 mg (86%), colourless oil. Ϫ IR (film): ν˜ ϭ 3435
ture was extracted exhaustively with diethyl ether and the organic (OH), 2925, 1685, 1670, 1650, 1635, 1625, 1575, 1560, 1540, 1520,
layers were dried (MgSO4) and concentrated. The crude product
was purified by CC (SiO2; CHCl3/ethyl acetate, 1:1); yield 4.00 g
1505, 1475, 1460, 1440, 1420, 1375, 1340, 1300, 1280, 1240, 1215,
1160, 1110, 1080, 1030, 980, 905, 820, 760 cmϪ1. Ϫ 1H NMR
(93%), colourless oil. Ϫ IR (film): ν˜ ϭ 3445 (OH), 2930, 2830, 1690 (CD3OD ): δ ϭ 7.13 (d, J ϭ 2.2 Hz, 1 H, Ar-H), 7.05 (dd, J1 ϭ
1
(CϭO), 1600, 1580 cmϪ1. Ϫ H NMR (CDCl3): δ ϭ 9.91 (s, 1 H,
8.0 Hz, J2 ϭ 2.2 Hz, 1 H, Ar-H), 7.00 (d, J ϭ 7.5 Hz, 1 H), 6.91
CHO), 7.86 (dd, J1 ϭ 8.4 Hz, J2 ϭ 1.8 Hz, 1 H, Ar-H), 7.68 (d, (d, J ϭ 8.4 Hz, 1 H), 6.88 (dd, J1 ϭ 8.4 Hz, J2 ϭ 2.6 Hz, 1 H, Ar-
J ϭ 2.2 Hz, 1 H, Ar-H), 7.08Ϫ7.06 (m, 2 H, Ar-H), 7.02 (d, J ϭ H), 6.76 (d, J ϭ 8.0 Hz, 1 H, Ar-H), 6.74 (d, J ϭ 1.8 Hz, 1 H, Ar-
8.4 Hz, 1 H, Ar-H), 6.98 (d, J ϭ 2.2 Hz, 1 H, Ar-H), 6.93Ϫ6.91
H), 6.71 (dd, J1 ϭ 7.5 Hz, J2 ϭ 1.8 Hz, 1 H, Ar-H), 6.68 (d, J ϭ
(m, 2 H, Ar-H), 6.83 (d, J ϭ 2.2 Hz, 1 H, Ar-H), 6.80 (dd, J1 ϭ 2.6 Hz, 1 H, Ar-H), 6.64 (d, J ϭ 8.4 Hz, 1 H, Ar-H), 6.59 (dd,
8.0 Hz, J2 ϭ 2.6 Hz, 2 H, Ar-H), 6.74 (d, J ϭ 2.2 Hz, 1 H, Ar-H), J1 ϭ 8.0 Hz, J2 2.2 Hz, 1 H, Ar-H), 6.55 (d, J ϭ 12.0 Hz, 1 H,
4.66 (s, 2 H, CH2OH), 3.83, 3.81, 3.74, 3.71 (s, each 3 H, OCH3), CHϭCH), 6.48 (d, J ϭ 2.2 Hz, 1 H, Ar-H), 6.46 (d, J ϭ 12.0
2.69 (br. s, 4 H, CH2CH2), 1.94 (br. s, 1 H, CH2OH). Ϫ 13C NMR Hz, 1 H, CHϭCH), 2.60Ϫ2.51 (m, 4 H, CH2CH2). Ϫ 13C NMR
(CDCl3): δ ϭ 191.1, 162.3, 159.0, 157.2, 155.3, 141.9, 141.8, 134.2,
(CD3OD): δ ϭ 157.9, 156.2, 153.9, 152.2, 144.7, 141.1, 137.1, 134.5,
132.8, 131.8, 131.7, 131.4, 131.2, 130.8, 129.7, 129.2, 128.9, 126.3, 134.3, 133.4, 132.6, 131.4, 130.9, 130.7, 130.6, 129.9, 128.8, 128.6,
118.7, 114.5, 111.2, 111.1, 110.9, 109.3, 65.3, 56.0, 55.9, 55.5, 55.2, 128.0, 127.3, 120.8, 117.7, 116.8, 113.8, 39.5, 38.6. Ϫ MS; m/z (%):
36.3, 36.1. Ϫ MS; m/z (%): 513 (5) [Mϩ], 330 (3), 272 (62), 258 423 (4) [Mϩϩ1], 422 (2) [Mϩ], 421 (4), 255 (5), 178 (12), 165 (12),
(100), 255 (19), 241 (22), 227 (8), 213 (8), 152 (8), 89 (15), 83 (14), 98 (14), 95 (12), 91 (28), 89 (16), 87 (18), 83 (38), 81 (22), 78 (100),
61 (12), 57 (18), 45 (12). Ϫ C32H32O6 (512.6): calcd. C 74.98, H
73 (23), 71 (22), 69 (22), 57 (49), 55 (59), 51 (27), 45 (46). Ϫ
6.29; found C 74.75, H 6.32.
C28H22O4 (422.5): calcd. C 79.60, H 5.25; found C 79.77, H 5.32.
Ϫ For reference data see ref.[16]
.
4-Methoxy-3-[2-methoxy-5-(5-methoxy-2-{2-methoxy-4-[(1,1,1-
triphenylphosphonio)methyl]phenyl}phenethyl)phenyl]benzaldehyde
Isoplagiochin D Tetramethyl Ether (53): 480 mg (1.00 mmol) of
Bromide (51): To a solution of 3.20 g (6.25 mmol) of benzyl alcohol the (Z)-stilbene 52 was hydrogenated according to GP 1 (ethyl ace-
50 in 40 ml of CH2Cl2 was added 0.60 ml (1.70 g, 6.25 mmol) of tate, 5% Pd/C, 3.5 bar, 24 h). The crude product was purified by
PBr3 and the mixture was stirred for 2 h at 20°C, washed with cold
satd. NaHCO3, dried (MgSO4) and concentrated. The crude and
CC (SiO2; CH2Cl2); yield 438 mg (91%), colourless crystals, m.p.
134°C. Ϫ IR (KBr): ν˜ ϭ 2920, 2845, 1610, 1575 cmϪ1. Ϫ 1H NMR
unstable benzyl bromide was converted directly to the phos- (CDCl3): δ ϭ 7.17Ϫ7.09 (m, 2 H, Ar-H), 7.05Ϫ7.00 (m, 2 H, Ar-
phonium salt according to GP 2.3 (toluene); yield 3.10 g (60%), H), 6.88Ϫ6.87 (m, 1 H, Ar-H), 6.85 (d, J ϭ 8.4 Hz, 1 H, Ar-H),
colourless salt, m.p. 184°C (ethyl acetate). Ϫ IR (KBr): ν˜ ϭ 2990, 6.78 (dd, J1 ϭ 8.4 Hz, J2 ϭ 2.6 Hz, 1 H, Ar-H), 6.71 (dd, J1 ϭ 8.4
2930, 2825, 1680 (CϭO), 1600 cmϪ1. Ϫ 1H NMR (CDCl3): δ ϭ
Hz, J2 ϭ 2.6 Hz, 1 H, Ar-H), 6.38 (m, 1 H, Ar-H), 6.33Ϫ6.26 (m,
9.84 (s, 1 H, CHO), 7.82Ϫ7.67 (m, 10 H, Ar-H), 7.57Ϫ7.51 (m, 8 2 H, Ar-H), 6.21 (m, 1 H, Ar-H), 3.81, 3.77, 3.75, 3.73 (s, each
H, Ar-H), 7.16Ϫ7.12 (m, 3 H, Ar-H), 6.97Ϫ6.90 (m, 2 H, Ar-H), 3 H, OCH3), 2.88Ϫ2.66 (m, 4 H, CH2CH2), 2.54Ϫ2.45 (m, 4 H,
6.82Ϫ6.68 (m, 4 H, Ar-H), 5.35 (d, J ϭ 14.1 Hz, 2 H, CH2P), 3.87 CH2CH2). Ϫ 13C NMR (CDCl3): δ ϭ 158.9, 156.7, 155.4, 143.6,
(s, 3 H, OCH3), 3.76 (s, 6 H, OCH3) 3.69 (s, 3 H, OCH3), 2.68 (br. 142.0, 135.6, 135.3, 134.4, 132.9, 131.7, 130.8, 131.4, 130.5, 129.1,
s, 4 H, CH2CH2). Ϫ 13C NMR (CDCl3): δ ϭ 191.0, 162.4, 159.1, 128.1, 126.8, 123.2, 120.7, 113.9, 111.2, 110.7, 110.2, 55.8, 55.7,
157.0, 155.4, 141.5, 139.5, 135.0, 134.6, 134.5, 133.9, 132.4, 132.1,
131.6, 131.1, 130.2, 130.1, 129.6, 129.2, 129.1, 128.9, 128.3, 127.7, 241 (12), 239 (26), 225 (10), 121 (10), 111 (14), 97 (18), 95 (13), 85
55.5, 55.1, 37.7, 36.9, 36.6, 36.0. Ϫ MS; m/z (%): 480 (100) [Mϩ],
126.4, 125.3, 122.9, 121.5, 118.4, 117.5, 114.8, 111.3, 110.9, 56.1,
56.0, 55.9, 55.1, 35.9, 35.6, 30.6.
(14), 83 (15), 81 (12), 71 (21), 69 (18), 57 (36), 55 (23). Ϫ C32H32O4
(480.6): calcd. C 79.97, H 6.71; found C 79.81, H 6.83.
Isoplagiochin C Tetramethyl Ether (52): 2.50 g (3.00 mmol) of
the phosphonium bromide 51 was subjected to a Wittig reaction
according to GP 3.2. Purification by CC (SiO2; CH2Cl2) afforded
Isoplagiochin D (54): 240 mg (0.50 mmol) of the tetramethyl
ether 53 was cleaved according to GP 4 (4.00 mmol BBr3, Ϫ78°C
Ǟ 20°C). The crude product was isolated by extraction with
1.07 g (74%), colourless viscous oil. Ϫ IR (film): ν˜ ϭ 2905, 1560, CH2Cl2 and purified by flash chromatography on RP-18 using
1
1535 cmϪ1. Ϫ H NMR (CDCl3): δ ϭ 7.21Ϫ7.19 (m, 1 H, Ar-H), methanol/H2O, 1:1; yield 175 mg (82%), colourless viscous oil. Ϫ
7.14Ϫ7.11 (m, 2 H, Ar-H), 7.08Ϫ7.02 (m, 2 H, Ar-H), 6.98Ϫ6.96 IR (film): ν˜ ϭ 3300 (OH), 2920, 2860, 1610, 1580, 1570, 1495, 1445,
(m, 1 H, Ar-H), 6.88Ϫ6.87 (m, 2 H, Ar-H), 6.83 (d, J ϭ 8.4 Hz, 1 1420, 1370, 1345, 1285, 1235, 1160, 1015, 960, 895, 865, 820, 730
1
H, Ar-H), 6.79 (dd, J1 ϭ 8.4 Hz, J2 ϭ 2.7 Hz, 2 H, Ar-H), 6.73 cmϪ1. Ϫ H NMR (CD3OD): δ ϭ 7.04 (dd, J1 ϭ 8.0 Hz, J2 ϭ 2.2
(d, J ϭ 8.0 Hz, 1 H, Ar-H), 6.66 and 6.60 (d, J ϭ 11.9 Hz, each 1 Hz, 1 H, Ar-H), 7.00 (d, J ϭ 7.5 Hz, 1 H, Ar-H), 6.96 (d, J ϭ 8.0
H, CHϭCH), 6.49 (d, J ϭ 2.2 Hz, 1 H, Ar-H), 3.83, 3.79, 3.78, Hz, 1 H, Ar-H), 6.91 (dd, J1 ϭ 8.0 Hz, J2 ϭ 2.2 Hz, 1 H, Ar-H),
3.74( s, each 3 H, OCH3), 2.88Ϫ2.63 (m, 4 H, CH2CH2). Ϫ 13C 6.79 (d, J ϭ 8.4 Hz, 1 H, Ar-H), 6.78 (d, J ϭ 2.6 Hz, 1 H, Ar-H),
NMR (CDCl3): δ ϭ 159.0, 156.3, 155.3, 143.7, 140.1, 135.5, 133.7,
6.70Ϫ6.67 (m, 3 H, Ar-H), 6.64 (d, J ϭ 1.3 Hz, 1 H), 6.47 (d, J ϭ
Eur. J. Org. Chem. 1998, 877Ϫ888
887

T. Eicher, S. Fey, W. Puhl, E. Büchel, A. Speicher
FULL PAPER
[8]
[9]
Riccardin C was synthesized in a 14-step sequence with 0.04%
overall yield: A. Gottsegen, M. Nogradi, B. Vermes, M. Kajtar-
Peredy, E. Bihatsi-Karsei, J. Chem. Soc., Perkin Trans. 1 1990,
315Ϫ320.
Syntheses on preparative scale are relevant for the systematic
screening of natural products on biological acitivites. We grate-
fully acknowledge the collaboration with the BASF AG, Lud-
wigshafen, the Landwirtschaftliche Versuchsstation Limburger-
hof, and the Bayer AG, Leverkusen, Zentrale Forschung, Fach-
bereich Leitstrukturforschung.
T. Kametani, Y. Hirai, M. Kajiwara, T. Takahashi, T. Fuku-
moto, Chem. Pharm. Bull. 1975, 23, 2634Ϫ2642.
D. C. Remy, S. W. King, D. Cochran, J. P. Springer, J. Hirsch-
field, J. Org. Chem. 1985, 50, 4120Ϫ4125.
R. M. Boden, Synthesis 1975, 784.
N. Miyaura, T. Yanagi, A. Suzuki, Synth. Commun. 1981, 11,
513Ϫ519.
2.2 Hz, 1 H), 6.37 (d, J ϭ 2.2 Hz, 1 H, Ar-H), 2.93Ϫ2.83 (m, 4 H,
CH2CH2), 2.78Ϫ2.64 (m, 4 H, CH2CH2). Ϫ 13C NMR (CD3OD):
δ ϭ 157.7, 155.5, 153.3, 152.9, 144.8, 143.4, 136.3, 134.7, 134.3,
132.9, 132.7, 130.7, 129.7, 128.7, 128.0, 127.1, 122.1, 118.0, 117.5,
116.7, 116.5, 113.8, 39.8, 39.3, 38.8, 37.0. Ϫ MS; m/z (%): 424 (61)
[Mϩ], 320 (12), 227 (14), 213 (100), 211 (81), 199 (15), 197 (15),
195 (19), 181 (11), 149 (12), 107 (70), 83 (12), 77 (11), 73 (10), 71
(15), 69 (17), 57 (36), 45 (10). Ϫ C28H24O4 (424.5): calcd. C 79.23,
[10]
[11]
H 5.70; found C 79.07, H 6.94. Ϫ For reference data see ref.[16]
.
[1]
H. D. Zinsmeister, H. Becker, T. Eicher, Angew. Chem. 1991,
103, 134Ϫ151; Angew. Chem. Int. Ed. Engl. 1991, 30, 130Ϫ147.
H. D. Zinsmeister, H. Becker, T. Eicher, R. Mues, Naturwiss.
Rundschau 1994, 47, 131Ϫ136.
[12]
[13]
[2]
[3]
[14]
[15]
[16]
Y. Oh-e, N. Miyaura, A. Suzuki, Synlett 1990, 221Ϫ223.
W. Watanabe, N. Miyaura, A. Suzuki, Synlett 1992, 207Ϫ210.
T. Hashimoto, S. Kanayama, Y. Kan, M. Tori, Y. Asakawa,
Chem. Lett. 1996, 9, 741Ϫ742.
M. Tori, M. Toyota, L. Harrison, K. Takikawa, Y. Asakawa,
Tetrahedron Lett. 1985, 4735Ϫ4738.
Y. Asakawa in Progress in the Chemistry of Organic Natural
Products (Eds.: E. Herz, G. W. Kirby, R. E. Moore, W. Steglich,
C. Tamm), Springer, Wien, New York, 1995, p. 5.
[4]
[5]
For the syntheses of Plagiochins see ref.[3] and Ph. D. thesis of
M. Scherer, Universität des Saarlandes, 1996.
[17]
[18]
For the biogenesis of cyclic bisbibenzyls Lunularin and Perrotte-
tins are discussed as precursors for oxidative coupling reactions,
Y. Asakawa, R. Matsuda, Phytochemistry 1982, 21, 2143Ϫ2144;
C.-L. Wu, H.-R. Lin, Phytochemistry 1997, 44, 101Ϫ105; T.
Yoshida, T. Hashimoto, S. Takaoka, Y. Kan, M. Tori, Y. Asa-
kawa, Tetrahedron 1996, 52, 14487Ϫ14500.
see ref.[3]
.
[6]
[7]
T. Eicher, M. Walter, Synthesis 1991, 469Ϫ473.
Marchantin I was synthesized in a 12-step sequence with 0.6%
overall yield: Z. Dienes, M. Nogradi, B. Vermes, M. Kajtar-
Peredy, Liebigs Ann. Chem. 1989, 1141Ϫ1143.
[97349]
888
Eur. J. Org. Chem. 1998, 877Ϫ888