Synthetic study of optically active and C2-symmetric novel ligand, 7,8-bis(benzyloxy)bicyclo[2.2.2]octa-2,5-diene and a tricarbonyliron complex

Article abstract of DOI:10.1039/b301271a

The 7,8-bis(benzyloxy)bicyclo[2.2.2]octa-2,5-diene derivatives have been synthesized via Diels-Alder reaction of optically active 5,6-bis(benzyloxy)cyclohexa-1,3-diene and dienophiles. The corresponding tricarbonyliron complexes have also been synthesized in enantiomerically pure form.

Full text of DOI:10.1039/b301271a

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Synthetic study of optically active and C2-symmetric novel ligand,
7,8-bis(benzyloxy)bicyclo[2.2.2]octa-2,5-diene and a tricarbonyliron
complex
Akiko Watanabe, Mariko Aso and Hiroshi Suemune*
Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan
Received 4th February 2003, Accepted 26th March 2003
First published as an Advance Article on the web 8th April 2003
The 7,8-bis(benzyloxy)bicyclo[2.2.2]octa-2,5-diene derivatives have been synthesized via Diels–Alder reaction of
optically active 5,6-bis(benzyloxy)cyclohexa-1,3-diene and dienophiles. The corresponding tricarbonyliron complexes
have also been synthesized in enantiomerically pure form.
Introduction
We recently, reported the asymmetric synthesis of both
enantiomers of 5,6-bis(benzyloxy)cyclohexa-1,3-diene and the
corresponding tricarbonyliron complex1a in the course of our
studies on the development of asymmetric reaction using a
metal catalyst with novel diene compounds as chiral lig-
ands.1 In this report, we describe the asymmetric synthesis of
5,6-bis(benzyloxy)bicyclo[2.2.2]oct-2-ene and 7,8-bis(benzyl-
oxy)bicyclo[2.2.2]octa-2,5-diene derivatives, and diene-tricarb-
onyliron complexes. So far, synthetic studies of σ-symmetric
bicyclo[2.2.2]octapolyenes have been reported via [4 ϩ 2] cyclo-
addition,2 however, there are few reports on Diels–Alder
reactions of C2-symmetric optically active cyclic dienes for the
synthesis of this framework.
Results and discussion
The Diels–Alder reaction of optically active 5,6-disubstituted
cyclohexa-1,3-dienes (1 and 2) with several dienophiles (3a–d)
was studied. Reaction of 1 and 3a,b gave [4 ϩ 2] cycloadducts
4a (95%) and 4b (97%) as the sole product, respectively. The
stereochemistry of the products was determined by the NOEs
1
between Ha and Hb in the H–1H NOESY spectra. In these
reactions, the selection of diene-faces may be negligible for the
stereochemistry of the product, and reactivity might be
enhanced by using both faces of diene because of the C2-sym-
metry of 1. The endo–exo selectivity is the key to determining
the stereochemistry, and complete endo-selective [4 ϩ 2] cyclo-
addition was observed in these cases.
The reaction of compounds 1, 2 and dimethyl acetylene-
dicarboxylate (3c) gave cycloadducts 4c and 5c in 93% and 90%
yields, respectively. The former required heating conditions, and
the latter proceeded in CH2Cl2 at room temperature (Scheme 1).
The reaction of 2 and 3c in refluxing benzene gave 5c in 72%
yield. In the reactions of Scheme 1, the dienophile–diene
ratios varied between 0.67 and 11, which gave satisfactory yields
of products. Among them, the use of a smaller amount of 3b
(0.67 equiv.) was required because the separation of 3b and
product 4b was difficult.
In the case of the reaction of 2 and 2-chloroacrylonitrile (3d),
the addition of amine base was required to prevent decom-
position of 2 and cycloadduct by acidic species derived from 3d
under heating conditions.3 In this reaction, cycloadduct 5d was
obtained in 69% yield as the sole product. The structure of 5d
was determined based on further derivatization using ( )-5d as
follows. Reduction of ( )-5d with LiAlH4 afforded an aziridine
derivative ( )-6 (61%) accompanied by an unexpected primary
amine ( )-7 (17%). The structure of ( )-6 and ( )-7 was
Scheme 1
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 1 7 2 6 – 1 7 2 9
T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 3
1726

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determined based on spectroscopic analyses. In 1H-NMR
spectrum of ( )-6, CH2 in the aziridine ring were observed at
δ 1.98 (1H, s) and 1.93 (1H, s). In 1H-NMR spectrum of com-
pound ( )-7, C2-Me was observed at δ 1.10 (3H, s), and C2-Me
carbon in 13C-CMR spectrum was observed at δ 31.7 (q).
The relative stereochemistry of ( )-7 was determined to be
1RS,2SR,4RS,7RS,8RS based on 1H,1H-NOESY spectrum,
in which correlations were observed between C7–Ha and
C2–NH2, C2–Me and C3–Hb, C2–Me and C6–Hc as illustrated
in Scheme 2. Considering that the reductive aziridine ring
cleavage of ( )-6 might afford ( )-7, the configuration at the
C2-position of ( )-7 should be derived from that of ( )-6. As a
plausible process for the formation of ( )-6, LiAlH4 reduc-
tion of the nitrile function of ( )-5d might afford an amino-
methyl intermediate A, and further intramolecular SN2-type
substitution might construct ( )-6. Based on this consider-
ation, the absolute stereochemistry of the C2-position of
optically active 5d was expected to be R. The above results
suggest that [4 ϩ 2] cycloaddition of 2 and 3d proceeded in
both complete exo-selective and regioselective manner. This
exo-selectivity might be attributable to the steric factor instead
of the secondary orbital effect.
Scheme 4 Reagents: i. KOH, DMSO, H2O, 83%; ii. p-Ts-NHNH2,
MeOH, rt, 94%; iii. BuLi, THF, Ϫ78 ЊC, 48%.
1
spectroscopic analyses. In the H-NMR spectrum, two kinds
of olefinic protons and two kinds of methine protons were
observed, this is attributable to the C2-symmetric property of
11, in addition to 11 carbon signals in the 13C-NMR spectrum.
Metal-diene complex formation was studied by using com-
pounds 5c and 11. In preliminary studies using diene 11 and
several metal species such as RhCl3, Fe2(CO)9, Mo(CO)6
and W(CO)6, only iron-tricarbonyl complex 12 was obtained in
78% yield under refluxing conditions in THF. In the use of
RhCl3 in EtOH, the reaction afforded a complex mixture, and
the use of Mo(CO)6 or W(CO)6 afforded the recovery of
substrate.1d,5 The reaction of 5c and Fe2(CO)9 gave a corre-
sponding iron-tricarbonyl complex 13 in 34% yield (Scheme 5).6
The structure of these complexes 12 and 13 was supported by
spectroscopic analyses.
Scheme 2
Next, the solvolysis of acetate function in 4a–c was per-
formed to study the stability and the possibility of derivation
of cycloadducts. Treatment of 4a,b with K2CO3 in MeOH at
room temperature afforded a complex mixture in both cases.
Reaction of 4c under the same conditions did not afford a
corresponding diol but dimethyl phthalate 8 in 74% yield.
This ring transformation was considered to proceed via retro-
Diels–Alder reaction starting from the corresponding alkoxide
anion B as shown in Scheme 3.
Scheme 5
Thus, novel diene compounds such as 4c, 5c and 11 have been
synthesized. We plan to study further the use of these com-
pounds as a chiral ligand of metal complex. Both enantiomers
of optically active ligands were considered to be necessary to
study the asymmetric reaction. For this purpose, both enantio-
mers of optically active compounds in this paper were
prepared.
Experimental
IR spectra were measured with a JASCO A-202 and Thermo-
Nicolet Avatar 320 KYD spectrometer. 1H-NMR and 13C-
NMR spectra were measured with a JEOL JNM-GX 270 or
Varian Oxford 400 or JNM-GX 500 spectrometer using CDCl3
as a solvent and tetramethylsilane (TMS) as an internal stand-
ard. Mass spectra were taken on a JEOL JMD-D-300 610 HS
and JEOL JMS-SX/SX-102A spectrometer. Optical rotations
were measured on a JASCO DIP-360 polarimeter and are given
in 10Ϫ1 deg cm2 g Ϫ1. For column chromatography, silica gel
(Nakarai Tesque, Silica Gel 60, 230–400 mesh) was used. All
organic solvent extracts were dried over anhydrous MgSO4.
Scheme 3
Next, compound 5d was transformed into C2-symmetric
(7R,8R)-7,8-bis(benzyloxy)bicyclo[2.2.2]octa-2,5-diene 11 in
the sequence of the following reactions. i. Conversion of 5d into
ketone 9 (83%) under basic conditions. ii. Conversion of 9 into
the corresponding p-tosylhydrazone 10 (94%). iii. Treatment of
10 with a strong base4 to afford the target molecule 11 (48%)
(Scheme 4). Structure of 11 was supported by the following
Diels–Alder reaction of 1, 2 and dienophiles 3a–c
Reaction of 1 and 3a. (R,R)-5,6-Bisacetoxycyclohexa-1,3-
diene 1 (180 mg, 0.9 mmol) and N-phenylmaleimide (3a,
165 mg, 0.9 mmol) were dissolved in CH3CN (1 ml) at room
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 1 7 2 6 – 1 7 2 9
1727

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temperature, and the whole was stirred at the same temperature
for 3 d. The reaction mixture was diluted with hexane (2 ml)
and the resulting precipitates were recrystallized from acetone
to afford 4a (317 mg, 95%) as colorless prisms. Mp 197–198 ЊC;
[α]2D4 = Ϫ61.7 (c = 1.4, CHCl3); δH (270 MHz, CDCl3) 7.49–7.36
(3H, m), 7.19 (2H, dd, J = 1.65, 8.25), 6.37–6.25 (2H, m), 4.85
(1H, s), 4.74 (1H, m), 3.48 (2H, d, J = 2.97), 3.37 (1H, dd,
J = 2.97, 8.25), 3.24 (1H, dd, J = 2.97, 8.25), 2.13 (3H, s), 2.07
(3H, s); νmax/cmϪ1 (KBr) 3045, 2950, 2920, 1740, 1700, 1490,
1375, 1350, 1220, 1200, 1165, 1050, 1025, 870; m/z (FAB) 370
[M ϩ H]ϩ; Anal. Calcd. For C20H19NO6: C, 65.03; H, 5.18; N,
3.79; Found: C, 65.05; H, 5.18; N, 3.79%. Ent-4a; [α]2D4 = ϩ62.9
(c = 1.54, CHCl3).
After removal of 3d in vacuo, the residue was purified by silica-
gel column chromatography (hexane–AcOEt = 10 : 1) to afford
5d (523 mg, 69%) as a yellow oil. [α]2D6 = Ϫ45.98 (c = 1.1, CHCl3);
δH (270 MHz, CDCl3) 7.37–7.28 (10H, m), 6.40 (1H, t, J = 6.93),
6.12 (1H, t, J = 6.93), 4.60–4.42 (4H, m), 3.94 (3H, s), 3.37–3.35
(2H, m), 2.93–2.87 (2H, m), 1.87 (1H, m); νmax/cmϪ1 (neat) 3060,
3030, 2950, 2860, 2240, 1600, 1480, 1445, 1350, 1200, 1080, 920,
730, 690; m/z (FAB) 380 ([M ϩ H]ϩ) [Calcd. For C23H21NO2Cl:
M Ϫ H. 378.126. Found: (M Ϫ H)ϩ 378.127 (FAB)]. Ent-5d;
[α]2D6 = ϩ43.8 (c = 1.0, CHCl3).
LiAlH4 reduction of ( )-5d. A solution of ( )-5d (760 mg,
2 mmol) in THF (10 ml) was added dropwise to the suspension
of LiAlH4 (320 mg, 4 mmol) in THF (10 ml) under an Ar
atmosphere at 0 ЊC. The reaction mixture was refluxed for 11 h.
The reaction was quenched by addition of 15% aqueous
sodium hydroxide. The resulting gel was filtered off and washed
with THF. The combined filtrates were dried, and the solvent
was removed in vacuo. The residue was purified by silica gel
column chromatography (ethyl acetate–methanol = 10 : 1) to
afford ( )-6 (163 mg, 23%) and ( )-7 (232 mg, 33%).
( )-6; 23% yield; a colorless oil; δH (270 MHz, CDCl3) 7.35–
7.23 (10H, m), 6.34–6.24 (2H, m), 4.61–4.44 (4H, m), 4.02 (1H,
s), 3.49 (1H, s), 2.91 (1H, t, J = 2.64), 2.08 (1H, t, J = 2.64), 1.94
(1H, dd, J = 2.0, 13.0), 1.68, 1.63 (1H, each, s), 1.54 (1H, d,
J = 13.0); νmax/cmϪ1 (neat) 3300, 3060, 3032, 2946, 2866, 1496,
1454, 1361, 1205, 1097, 1074, 1028, 908, 780, 732, 698; m/z
(FAB) 348 ([M ϩ H]ϩ), 362 ([M ϩ Na]ϩ); [Calcd. For C23H26-
NO2: M ϩ H. 348.196. Found: (MϩH)ϩ 348.195 (FAB)].
( )-7; 33% yield; a colorless oil; δH (500 MHz, CDCl3) 7.35–
7.23 (10H, m), 6.25 (1H, t, J = 6.87), 6.15 (1H, t, J = 6.87), 4.58
(1H, d, J = 11.9), 4.53 (1H, d, J = 11.9), 4.49 (1H, d, J = 11.9),
4.45 (1H, d, J = 11.9), 4.03 (1H, s), 3.43 (1H, t, J = 1.83),
2.88 (1H, dd, J = 2.97, 6.41), 2.50 (1H, dd, J = 2.74, 6.4), 1.77
(1H, dd, J = 2.28, 13.04), 1.69 (2H, s), 1.21 (1H, dq, J = 1.61,
13.05), 1.10 (3H, s); δC (125 MHz, CDCl3) 138.4 (s), 138.2 (s),
133.3 (d), 129.6 (d), 128.1 (d), 128.0 (d), 127.5 (d), 127.4 (d),
127.3 (d), 127.2 (d), 81.7 (d), 80.1 (d), 70.4 (t), 70.0 (t), 52.4 (s),
48.1 (d), 35.5 (d), 35.4 (t), 31.7 (q); νmax/cmϪ1 (neat) 3366, 3289,
3050, 3030, 2940, 2866, 1586, 1496, 1453, 1364, 1205, 1094,
1074, 1028, 909, 734, 697; m/z (FAB) 350 ([M ϩ H]ϩ) [Calcd.
For C23H28NO2: M ϩ H. 350.212. Found: (M ϩ H)ϩ 350.212
(FAB)].
Reaction of 1 and 3b. Compound 1 (300 mg, 1.5 mmol) and
α-naphthoquinone (3b, 160 mg, 1 mmol) were dissolved in tolu-
ene (1 ml), and the whole was refluxed for 10 h. After cooling to
room temperature, the reaction mixture was diluted with hex-
ane (2 ml), then the resulting precipitate was recrystallized from
EtOH to afford 4b (230 mg, 97% based on 3b, 65% based on 1)
as colorless prisms. Mp 148–149 ЊC; [α]2D4 = Ϫ52.6 (c = 0.76,
CHCl3); δH (270 MHz, CDCl3) 8.04 (2H, dd, J = 3.3, 5.94), 7.73
(2H, dd, J = 3.3, 5.94), 6.27–6.15 (2H, m), 4.94 (1H, t, J = 2.31),
4.71 (1H, m), 3.63 (2H, dd, J = 2.64, 5.94), 3.54 (1H, dd,
J = 2.64, 10.23), 3.38 (1H, dd, J = 2.64, 10.23), 2.13 (3H, s), 2.06
(3H, s); νmax/cmϪ1 (KBr) 3040, 2950, 1730, 1670, 1650, 1570,
1355, 1345, 1265, 1215, 1040, 1020, 1000, 725, 700; m/z (FAB)
355 ([M ϩ H]ϩ); Anal. Calcd. for C20H18O6: C, 67.79; H, 5.12;
Found: C, 67.67; H, 5.15%. Ent-4b; [α]2D4 = ϩ51.8 (c = 1.34,
CHCl3).
Dimethyl (1R,4S,7R,8R)-7,8-bisacetoxybicyclo[2.2.2]octa-2,5-
diene-2,3-dicarboxylate 4c
Compound 1 (370 mg, 1.8 mmol) and dimethyl acetyl-
enedicarboxylate 3c (2.5 ml, 20 mmol) were dissolved in ben-
zene (2 ml) and the whole was refluxed for 4 h. After removal of
the solvent in vacuo, the residue was purified by silica-gel
column chromatography (hexane–AcOEt = 4 : 1) to afford 4c
(563 mg, 93%) as a yellow oil. [α]2D2 = Ϫ96.4 (c = 0.93, CHCl3);
δH (270 MHz, CDCl3) 6.52–6.45 (2H, m), 4.75 (1H, dd, J = 1.65,
3.30), 4.59 (1H, dd, J = 1.65, 3.30), 4.21 (2H, ddd, J = 2.64, 5.28,
10.56), 3.82 (3H, s), 3.79 (3H, s), 2.05 (3H, s), 2.04 (3H, s);
νmax/cmϪ1 (neat) 3070, 3000, 2960, 2850, 1740, 1650, 1430, 1360,
1350, 1250, 1140, 1165, 1070, 1040, 950, 890; m/z (FAB) 339
([M ϩ H]ϩ) [Calcd. For C16H19O8: M ϩ H. 339.108. Found: (M
ϩ H)ϩ 339.109 (FAB)]. Ent-4c; [α]2D2 = ϩ110.0 (c = 1.33, CHCl3).
Solvolysis of 4c. K2CO3 (10 mg) was added to a stirred solu-
tion of 4c (162 mg, 0.48 mmol) in MeOH (1 ml) at room tem-
perature. After being stirred for 2 h at room temperature, water
was added to the reaction mixture. The whole was extracted
with ethyl acetate. The extracts were combined, dried over
MgSO4 and condensed in vacuo. The obtained residue was
purified by column chromatography (hexane–AcOEt = 2 : 1) to
give dimethyl phthalate 8 (70 mg, 74%).
Dimethyl (1R,4S,7R,8R)-7,8-bis(benzyloxy)bicyclo[2.2.2]-
octa-2,5-diene-2,3-dicarboxylate 5c
(R,R)-5,6-Bis(benzyloxy)cyclohexa-1,3-diene 2 (600 mg, 2
mmol) and 3c (0.5 ml, 4 mmol) were dissolved in CH2Cl2 (2 ml)
and the whole was stirred for 4 d at room temperature. After
removal of the solvent in vacuo, the residue was purified by
column chromatography (hexane–AcOEt = 15 : 1) to afford 5c
(764 mg, 88%) as a yellow oil. [α]2D6= Ϫ106.9 (c = 1.16, CHCl3);
δH (270 MHz, CDCl3) 7.36–7.24 (10H, m), 6.46–6.37 (2H, m),
4.64 (1H, d, J = 11.88), 4.57 (1H, d, J = 11.88), 4.46 (1H, d,
J = 11.88), 4.43 (1H, d, J = 11.88), 4.28 (1H, dd, J = 2.64, 5.28),
4.16 (1H, dt, J = 2.64, 5.28), 3.77(5) (3H, s), 3.77(1) (3H, s), 3.58
(1H, d, J = 2.31), 3.46 (1H, dd, J = 1.65, 2.97); νmax/cmϪ1 (neat)
3070, 3000, 2960, 2850, 1740, 1650, 1430, 1360, 1350, 1250,
1140, 1165, 1070, 1040, 950, 890, 810, 760, 720; m/z (FAB) 435
([M ϩ H]ϩ) [Calcd. For C26H27O6: M ϩ H. 435.181 Found:
435.182 (M ϩ H)ϩ (FAB)]. Ent-5c; [α]2D6 = ϩ99.3 (c = 1.00,
CHCl3).
(1S,4R,7R,8R)-7,8-Bis(benzyloxy)bicyclo[2.2.2]oct-5-en-2-one
9
Aqueous solution of 50% KOH (2 ml) was added to a stirred
solution of 5d (1.87 g, 4.9 mmol) in DMSO (5 ml) at room
temperature. After being stirred for 2 d at the same temperature,
the whole was poured into water (80 ml) and extracted with
ether. The combined extracts were washed with brine and dried.
After removal of the solvent in vacuo, the residue was purified
by silica-gel column chromatography (hexane–AcOEt = 3 : 1) to
afford 9 (1.36 g, 83%) as a yellow oil. [α]2D6 = ϩ154.9 (c = 1.00,
CHCl3); δH (500 MHz, CDCl3) 7.38–7.26 (10H, m), 6.45 (1H,
dt, J = 1.14, 6.87), 6.15 (1H, t, J = 6.87), 4.57 (2H, dd, J = 2.75,
11.9), 4.48 (2H, dd, J = 3.2, 11.9), 3.79 (1H, s), 3.69 (1H, m),
3.46 (1H, d, J = 5.72), 3.17 (1H, m), 2.44 (1H, dd, J = 1.83,
18.58), 1.96 (1H, ddd, J = 2.06, 3.21, 18.54); νmax/cmϪ1 (neat)
3055, 3025, 2860, 1720, 1605, 1490, 1445, 1395, 1350, 1305,
Reaction of 2 and 3d. A mixture of 2 (600 mg, 2 mmol),
2-chloroacrylonitrile 3d (0.6 ml, 10 mmol) and 2,6-lutidine
(0.12 ml, 2 mmol) was stirred at 95 ЊC for 12 h without solvent.
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 1 7 2 6 – 1 7 2 9
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1200, 1175, 1080, 1020; m/z (FAB) 335 ([M ϩ H]ϩ) [Calcd. For
C22H23O3: M ϩ H. 335.165 Found: (M ϩ H)ϩ 335.162 (FAB)].
Ent-9; [α]2D6 = Ϫ147.6 (c = 1.01, CHCl3).
column with ether. The ether eluent was concentrated in vacuo.
The residue was purified by silica-gel column chromatography
(hexane–ethyl acetate = 10 : 1) to give 12 (236 mg, 78%)
as a yellow oil. [α]2D5 = Ϫ67.0 (c = 1.0, CHCl3); δH (270 MHz,
CDCl3) 7.37–7.28 (10H, m), 4.52 (2H, d, J = 11.9), 4.43 (2H, d,
J = 11.9), 3.81–3.76 (2H, m), 3.14–3.09 (4H, m), 3.00–2.95 (2H,
m); νmax /cmϪ1 (neat) 3063 (m), 3030 (m), 2967 (m), 2867 (s),
2025 (s), 1944 (vs), 1497 (m), 1454 (m), 1357 (m), 1211 (m),
1093 (s), 1027 (m), 737 (m), 698 (s); m/z (FAB) 458 ([M]ϩ)
[Calcd. For C25H22O5Fe: M. 458.082 Found: Mϩ 458.083
(FAB)]. Ent-12; [α]2D5 = ϩ61.0 (c = 1.3, CHCl3).
p-Tosylhydrazone of (1S,4R,7R,8R)-7,8-bis(benzyloxy)bicyclo-
[2.2.2]oct-5-en-2-one 10
A mixed solution of 9 (250 mg, 0.75 mmol) and p-tosylhydra-
zine (140 mg, 0.75 mmol) in MeOH (2 ml) was stirred at room
temperature for 1 d. After removal of the solvent in vacuo,
the residue was purified by silica-gel column chromatography
(hexane–AcOEt = 2 : 1) to afford 10 (355 mg, 94%) as colorless
solids. [α]2D4 = ϩ34.7 (c = 1.03, CHCl3); δH (270 MHz, CDCl3)
7.81 (2H, d, J = 8.25), 7.37–7.22 (12H, m), 6.29 (1H, t, J = 6.6),
6.17 (1H, t, J = 6.6), 4.56–4.36 (4H, m), 3.59 (1H, d, J = 4.95),
3.54 (1H, m), 3.48 (1H, m), 3.10 (1H, m), 2.40 (3H, s), 2.34 (1H,
dd, J = 2.31, 16.82), 1.78 (1H, dd, J = 1.64, 13.86); νmax/cmϪ1
(KBr) 3190, 3025, 2860, 1730, 1650, 1595, 1490, 1450, 1385,
1355, 1320, 1250, 1150, 1080, 1010, 915, 810, 725, 680; m/z
(FAB) 503 ([M ϩ H]ϩ) [Calcd. For C29H31N2O4S: M ϩ H.
503.201 Found: (M ϩ H)ϩ 503.202 (FAB)]. Ent-10; [α]2D4 = Ϫ31.8
(c = 1.02, CHCl3).
(1R,4S,7R,8R)-7,8-Bis(benzyloxy)-2,3-bis(methoxycarbonyl)-
bicyclo[2.2.2]octa-2,5-dienyltricarbonyliron 13
A similar procedure described to prepare 12 using iron non-
acarbonyl (1.5 g, 4 mmol) and 5c (870 mg, 2 mmol) in 4 h
reaction afforded 13 (390 mg, 34%) as a yellow oil. [α]2D6 = ϩ20.6
(c = 0.88, CHCl3); δH (270 MHz, CDCl3) 7.37–7.23 (10H, m),
4.65 (1H, d, J = 12.2), 4.51 (1H, q, J = 3.3), 4.42 (2H, dd,
J = 2.64, 12.21), 4.02 (1H, m), 3.83 (2H, dt, J = 0.99, 5.61),
3.75 (1H, m), 3.72 (3H, s), 3.69 (1H, m), 3.66 (3H, m), 3.61
(1H, t, J = 2.64), 3.11 (1H, dd, J = 1.98, 2.97); νmax /cmϪ1
(neat) 3030 (w), 2950 (m), 2867 (w), 2051 (s), 1967 (vs), 1708 (s),
1496 (w), 1454 (m), 1436 (m), 1401 (m), 1343 (m), 1306 (m),
1235 (s), 1092 (s), 738 (m), 698 (m), 676 (m); m/z (FAB) 575
([M ϩ H]ϩ) [Calcd. For C29H27O9Fe: M ϩ H. 575.101 Found:
(M ϩ H)ϩ 575.099 (FAB)]. Ent-13; [α]2D6 = Ϫ19.5 (c = 0.88,
CHCl3).
(7R,8R)-7,8-Bis(benzyloxy)bicyclo[2.2.2]octa-2,5-diene 11
To a solution of 10 (500 mg, 1 mmol) in THF (40 ml) was added
a 15% solution of butyllithium in hexane (12.6 ml, 4 mmol)
at Ϫ78 ЊC under an Ar atmosphere. The whole was stirred at
Ϫ78 ЊC for 20 min, then allowed to warm to room temperature
for 2 h. The reaction was quenched by the addition of MeOH
(2 ml) and saturated aqueous NH4Cl. After removal of organic
solvent in vacuo, the aqueous layer was extracted with CH2Cl2.
The extracts were dried and condensed in vacuo. The obtained
residue was purified by silica-gel column chromatography
(hexane–AcOEt = 5 : 1) to give 11 (154 mg, 48%) as a yellow oil.
[α]2D7 = Ϫ96.1 (c = 1.031, CHCl3); δH (270 MHz, CDCl3) 7.37–
7.24 (10H, m), 6.43–6.31 (4H, m), 4.52 (4H, dd, J = 12.21,
27.38), 3.81–3.76 (2H, m), 3.46 (1H, t, J = 1.65); δC (100 MHz,
CDCl3) 138.3 (s), 133.8 (d), 131.5 (d), 128.2 (d), 127.6 (d), 127.4
(d), 83.9 (d), 70.8 (t), 41.4 (d); νmax/cmϪ1 (neat) 3070, 3045, 2980,
2870, 1590, 1495, 1450, 1100, 1030, 740, 705, 670; m/z (FAB)
317 ([M Ϫ H]ϩ) [Calcd. For C22H21O2: M Ϫ H. 317.158 Found:
(M Ϫ H)ϩ 317.162 (FAB)]. Ent-11; [α]2D7 = ϩ94.1 (c = 1.0,
CHCl3).
References
1 (a) A. Watanabe, T. Kamahori, M. Aso and H. Suemune, J. Chem.
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K. Sakai, Tetrahedron: Asymmetry, 1995, 6, 55; (c) J. Gawronski,
K. Gawronska, G. Buczak, A. Katrusiak, P. Skowronek and
H. Suemune, Tetrahedron: Asymmetry, 1996, 7, 301; (d ) A. Taka-
hashi, M. Aso, M. Tanaka and H. Suemune, Tetrahedron, 2000, 56,
1999 and references cited therein.
2 (a) T. Ohwada, I. Okamoto, N. Haga and K. Shudo, J. Org. Chem.,
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3 M. Ohkita, O. Nishizawa, T. Tsuji and S. Nishida, J. Org. Chem.,
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4 R. H. Shapiro and M. J. Heath, J. Am. Chem. Soc., 1967, 89, 5734.
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C24.
(7R,8R)-7,8-Bis(benzyloxy)bicyclo[2.2.2]octa-2,5-dienyltricarb-
onyliron 12
Iron nonacarbonyl (520 mg, 1.45 mmol) was added to a solu-
tion of 11 (210 mg, 0.66 mmol) in THF (15 ml) under an Ar
atmosphere at room temperature. The whole was refluxed for
1 h. After cooling, the whole was passed though short silica-gel
6 H.-J. Knölker, B. Ahrens, P. Gonster, M. Heininger and P. G. Jones,
Tetrahedron, 2000, 56, 2259 and references cited therein.
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 1 7 2 6 – 1 7 2 9
1729