Synthesis of hydroquinone-, biphenol-, and binaphthol-containing aza macroheterocycles via regioselective hydroformylation and reductive amination

Article abstract of DOI:10.1016/j.tet.2003.08.012

Rhodium(I) catalyzed regioselective hydroformylation of diolefins and subsequent reductive amination of the dialdehydes in the presence of α,ω-diamines is applied to azamacroheterocyclic ring synthesis. Starting from aromatic diallyl ethers of hydroquinone, biphenol and binaphthol 20-28 membered macroheterocycles were obtained in up to 78% yield.

Full text of DOI:10.1016/j.tet.2003.08.012

Tetrahedron 59 (2003) 8265–8274
Synthesis of hydroquinone-, biphenol-, and binaphthol-containing
aza macroheterocycles via regioselective hydroformylation and
reductive amination
*
Goran Angelovski and Peter Eilbracht
¨
Fachbereich Chemie, Organische Chemie I, Universitat Dortmund, Otto-Hahn-Strasse 6, 44221 Dortmund, Germany
Received 9 May 2003; revised 2 July 2003; accepted 1 August 2003
Abstract—Rhodium(I) catalyzed regioselective hydroformylation of diolefins and subsequent reductive amination of the dialdehydes in the
presence of a,v-diamines is applied to azamacroheterocyclic ring synthesis. Starting from aromatic diallyl ethers of hydroquinone, biphenol
and binaphthol 20–28 membered macroheterocycles were obtained in up to 78% yield.
q 2003 Elsevier Ltd. All rights reserved.
1. Introduction
from olefins and amines.7 Thus the olefin components react
under hydroformylation conditions (CO, H2, rhodium
catalyst) in the presence of amines in an overall ‘hydro-
aminomethylation’ addition reaction. We recently reported
successful applications of this tandem reaction in the
synthesis of macroheterocycles from diolefins and diamines
in comparatively high yields.8
Macroheterocycles containing chiral subunits are desired
synthetic targets due to their increasing use as tools in chiral
recognition1 and as ligands in asymmetric metal catalysis.2,3
Nonnatural atropisomeric biaryl systems with axial
chirality, e.g. 2,20-substituted 1,10-binaphthyls, are available
in both enantiomeric forms and therefore frequently
integrated into macroheterocyclic systems and used for
various applications.2
2. Results and discussion
There are several methods available for the synthesis of
medium-and large-sized heterocyclic systems.4 The most
common access is provided by the Richman–Atkins
approach,5 which involves nucleophilic substitution of
a,v-dihalides, -ditosylates or -dimesylates with a,v-
ditosylamides or a,v-diols in the presence of base.
However, with this approach the starting materials are
sometimes difficult to obtain and all nitrogen atoms in the
final macrocycle generally have to be protected.
In this work we report the application of this procedure in
the synthesis0 of azamacroheterocycles containing hydro-
quiono0ne, 1,1 -biphenol and finally the axially chiral (R)- or
(S)-1,1 -binaphthol units (Scheme 1). The diolefinic build-
ing blocks were prepared as diallylic ethers of these
phenolic diols.
In one of the alternative approaches azamacroheterocyclic
systems are synthesized starting from dialdehydes and
diamines via diimine formation.6 Frequently these diimines
are reduced to saturated amines in a second step. This type
of reductive amination of aldehydes can also be performed
in a one step procedure and furthermore conveniently be
combined with an in situ generation of the aldehydes via
hydroformylation in a single reaction sequence starting
Scheme 1.
With these substrates, however, possible Claisen rearrange-
ments occuring at elevated temperatures had to be prevented
by choosing appropriate conditions. Furthermore, in order to
prevent the formation of regioisomeric aldehydes (n,n,
n,iso, iso,iso) which are expected, when performing
hydroformylation with unsubstituted diallyl systems, bis-
methylallyl systems of type 1a-c were used. Here, according
to ‘Keuleman’s rule’9 hydroformylation is expected to occur
only in the terminal position. On the other hand, however,
Keywords: macrocycles; hydroaminomethylation; regioselective
hydroformylation; reductive amination; rhodium catalysis; chiral ligands;
BINOL.
*
Corresponding author. Tel.: þ49-231-755-3858; fax: þ49-231-7555363;
e-mail: peter.eilbracht@udo.edu
0040–4020/$ - see front matter q 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2003.08.012

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G. Angelovski, P. Eilbracht / Tetrahedron 59 (2003) 8265–8274
Scheme 2.
upon hydroformylation of the methallylic group two new
stereogenic centers are generated, leading to a mixture of
meso and D,L stereoisomers. Use of the chiral BINOL unit
should reveal a possible stereocontrol.
(808C instead of 1208C) in order to prevent possible Claisen
rearragement of the aromatic allyl ethers at temperatures
higher than 90–1008C. The rhodium catalyst was changed
from [Rh(cod)Cl]2 to [Rh(acac)(CO)2], since the former is
more active at higher while the latter is more active at lower
temperatures. As shown in Table 1 the yields of macro-
cycles 3a,b, 4a,b, and 5a,b are comparetively high.
As model compounds the diamine units 2a,b were easily
prepared from tetramethylene diamine and hexamethylene
diamine.10a,b Monobenzyl protection of both amino groups
prevents overalkylation and leaves the option to prepare
cryptand type molecules after debenzylation followed by a
second hydroaminomethylation of the resulting macrocyclic
diamine with the same or a different diolefin as shown
before.8a Furthermore, the resulting free NH groups can be
used to attach side-chains (e.g. long hydrophobic chains), or
polymer units.
The best yields (78%) were observed for the macrocyclic
compounds 5a and 5b (Scheme 3) containing the S-BINOL
unit. This findings are establishing the hitherto best results
in synthesis of macroheterocycles via hydroaminomethyl-
ation.
According to this procedure, as expected, exclusively the
n,n-dialdehydes and macrocycles thereof are formed, but
with generation of two new stereocenters at both carbons
bearing the methyl groups. Thus, the final products are
obtained as a mixture of enantiomers resp. diastereoisomers
(R,S,R,R,S,S), which could not be separated. According to
As compared to our previous work,8a for the hydroamino-
methylation of bis-methylallyl phenyl ethers (1a-c,
Scheme 2) in the presence of diamines 2a,b milder
conditions could be used. Lower temperatures were chosen
1
the H NMR spectra 3a,b are obtained as a 1:1 mixture of
the DL and meso isomers. 4a,b and 5a,b are also formed as a
mixture of stereoisomers with approximately 1:1 ratio. For
further clarification of the stereocontrol during the hydro-
formylation step aldehyde 5c (Scheme 4) was prepared in
the absence of the diamines 2a,b in a control experiment.
Table 1. Hydroaminomethylation reaction of bis-methylallyl phenyl ethers
1a-c with 2a,b
Entry
Ar
Diamine
Product
Yield (%)
1
1
2
3
4
5
6
Phenyl-
Phenyl-
2a
2b
2a
2b
2a
2b
3a
3b
4a
4b
5a
5b
64
59
68
75
78
78
Here again according to H NMR three stereoisomers are
detectable in a statistical 1:2:1 ratio (Saxial,R,R/Saxial,R,Sþ
axial,R,SþSaxial,S,R/Saxial,S,S). Thus no stereocontrol of the
BINOL unit is effective during hydroformylation under the
chosen conditions.
1,10-Biphenyl-
1,10-Biphenyl-
S-(þ)-binaphthyl-
S-(þ)-binaphthyl-
Scheme 3.

G. Angelovski, P. Eilbracht / Tetrahedron 59 (2003) 8265–8274
8267
hydroformylation of the diolefins in the presence of the
XANTPHOS ligand and the catalyst, isolation and charac-
terization of the n,n-dialdehyde and then converting these in
a second autoclave reaction in the presence of the diamine
and the same rhodium catalyst with 40–50 bar of hydrogen.
The yields are given in Table 3 and, with one exeption,
range from 43 to 71%.
Scheme 4.
In order to avoid these complications with the newly
generated stereogenic centers from the methallyl groups, the
unsubstituted allyl ethers 6a-c of hydroquionone, 1,10-
biphenol and (R)-1,10-binaphthol were prepared and con-
verted under hydroformylation conditions in the presence of
BIPHEPHOS11 and XANTPHOS12a (Scheme 5) to control
the required regioselectivity towards the n,n-dialdehydes.
Table 3. Reductive amination of the aldehydes 7a-c with diamines 2a,b
Entry
Aldehyde
Diamine
Product
Yield (%)
1
2
3
4
5
6
7a
7a
7b
7b
7c
7c
2a
2b
2a
2b
2a
2b
8a
8b
9a
9b
10a
10b
52
48
43
29
50
71
The overall yields in the stepwise procedure (hydroformyl-
ation and reductive amination) varied from 18 to 57% for
the macrocycles 8a,b, 9a,b, and 10a,b, whereas yields using
the tandem hydroformylation in the case of the methallyl
ethers 1a-c reaction to form macrocycles 3a,b, 4a,b, and
5a,b were in the range of 59–76%. If, however, comparing
these results with classical methods of reductive
amination14 using NaBH3CN or Na(OAc)3BH as reducing
agents, for 9a a yield of only 32% and for 9b of only 19%
was obtained. Interestingly, to our knowledge, there are
only few examples for the synthesis of azamacrohetero-
cycles via reductive amination starting from dialdehydes
and secondary diamines. In the examples presented here the
comparably high yields with the rhodium catalyzed
reductive ammination may be due to a template effect of
the rhodium during ring closure, which is even more
effective in the tandem procedure with lower stationary
concentrations of the dialdehydes.
Scheme 5.
The first runs with BIPHEPHOS were unsuccessful, since
this ligand is not sufficiently stable under the conditions
required, therefore XANTPHOS (Scheme 5) was used as the
ligand.
It is known that XANTPHOS can be used even under
harsher conditions (up to 1208C) without decomposition and
with good regioselectivities.12b Under the conditions used
here (708C, CO/H2 20 bar), the desired n,n-dialdehydes
were obtained in up to 80% yield (Table 2).
In contrast to the NMR spectra of 8b, 9a, 9b, and 10b those
of the products 8a, and 10a showed splitted signals for the
N-benzyl methylene and the oxygen neighbouring methyl-
ene protons. These splittings are changing towards single
signals upon heating (8a). This is attributed to different rigid
stereoisomeric conformations of the ring and/or different
‘frozen’ pyramidal geometries at the nitrogens with the
benzyl groups either on the same side or on different sides of
the ring. At room temperature this is not observed with
macrocycles 8b, 9b, and 10b containing the longer
hexamethylene diamine chain. Thus the molecular
dynamics of the products obtained appear to be very
sensitive to the chain length of the subunits. These effects
may also influence the tendency of ring closure and the
corresponding yields for the individual macrocycles. The
results presented here, however do not show a clear
tendency in this direction.
Table 2. Hydroformylation of 6a-c in the presence of XANTPHOS
Entry
Ar
Aldehyde
Yield (%)
1
2
3
Phenyl-
1,10-Biphenyl-
R-(2)-1,10-binaphthyl-
7a
7b
7c
78
63
80
The regioselectivity with use of this ligand for allylic ethers
in the best cases ranges in the area of 90–95% (n/iso).
Therefore if using a diolefin, the yield of n,n-dialdehyde
cannot be expected to be better than 80–85%. Heteroallyl
compounds in the absence of any ligands usually prefer
hydroformylation to form the iso-product (1:2 n/iso),13 thus
use of XANTPHOS in the present case gives satisfying
results.
For comparison selected examples of unsaturated ethers as
diolefins other than allyl ethers were stepwise converted
under slightly modified reaction conditions as described
above to form macroheterocycles with up to 28 membered
rings (Table 4, Scheme 6).
First control experiments of a tandem hydroaminomethyl-
ation conversion of the diolefins in the presence of diamines
directly to the macrocycles revealed that XANTPHOS as an
additional ligand controlling the regioselectivity under the
conditions used is not efficient in the presence of the amines.
Consequently macrocycles 8a,b, 9a,b, and 10a,b were
prepared in a stepwise manner, with first running the
Harsher reaction conditions had to be used for the
hydroformylation step in order to obtain the dialdehydes.

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G. Angelovski, P. Eilbracht / Tetrahedron 59 (2003) 8265–8274
Table 4. Regioselective hydroformylation of 11a,b and reductive
amination of 12a,b with diamines 2a,b
chiral aromatic subunits in good yields and selectivities. The
diamine unit as well as the diolefin unit can be varied in
many different ways as already shown in our previous
reports.7,8 Continuing these investigations the method offers
various options for fine-tuning the coordination properties
and geometries of ligands for transition metal catalysts or
hosts for molecular recognition.
Entry
Ar
n
Aldehyde Yield
(%)
m
Product Yield
(%)
1
2
3
Phenyl
S-(þ)-1,10-binaphthyl
3
4
4
12a
12b
12b
74
58
58
5
3
5
13a
13b
13c
53
77
78
S-(þ)-1,10-binaphthyl
Scheme 6.
While typical hydroformylation conditions for O-allylic
olefins were 20 bar of CO/H2 pressure (1:1) and tempera-
tures of 708C, for aldehyde 11a we had to use temperatures
of 120 and 1008C for 11b. In both cases the pressure had to
be increased to 60–80 bar CO/H2 (1:1). The conditions for
the reductive amination step were maintained. The results
compiled in Table 4 again show good yields and
selectivities.
4. Experimental
4.1. General remarks
All chemicals were purchased from commercial sources. 1H
and 13C NMR spectra were recorded at room temperature
with a Bruker DRX 400 and DRX 500 spectrometers using
CDCl3 as solvent and TMS as an internal standard. Infrared
spectra were recorded with a Nicolet Impact 400 D
spectrometer using neat compounds as films between
NaCl plates or as disks with KBr and only the major
bands are noted. Mass spectra were recorded with a JEOL
JMS-SX 102A spectrometer. Elemental analyses were
performed with a Leco CHNS-932 analyzer.
Unexpectedly with increasing ring size compound 13a
according to NMR showed the same rigidity characteristics
as previously described for compounds 8a and 10a while
this could not be observed for compounds 13b or 13c. After
debenzylation of 13a to the secondary diamine ring system
14 (Scheme 7) the observed signal splitting at the
O-neighbouring methylene groups disappeared, thus clearly
showing that the benzyl groups are responsible for this
effect.
Pressure reactions were carried out in autoclaves (250 ml,
PTFE insert) from Berghof, Eningen. After charging the
autoclave with the starting material, the catalyst precursor,
and the solvent (1,4-dioxane or toluene), the reactor was
flushed with argon, pressurised with hydrogen and carbon
monoxide, and heated to the required reaction temperature.
Following the reaction, the solvent was removed by rotary
evaporation and products were purified by column chroma-
tography on silica gel 60 (70–230 mesh ASTM) from
Macherey-Nagel GmbH & Co. KG.
4.1.1. Preparation of 7,12-dibenzyl-4,15-dimethyl-2,17-
dioxa-7,12-diaza-bicyclo[16.2.2]docosa-1(21)18(22),19-
triene (3a). 1,4-Bis-(2-methyl-allyloxy)-benzene (1a)15a
(77 mg, 0.35 mmol), N,N0-dibenzyl-butane-1,4-diamine
(2a)10a (81 mg, 0.30 mmol) and [Rh(acac)(CO)2] (4 mg,
16 mmol) were dissolved in 40 ml of 1,4-dioxane and placed
in the autoclave. The autoclave was pressurised with 80 bar
CO/H2 (1:1) and heated at 808C for 3 days. After cooling the
solvent was removed in a rotary evaporator and the crude
mixture was purified by column chromatography (silica gel,
Scheme 7.
3. Conclusion
In conclusion, the procedure described here shows a high
potential for a versatile synthesis of various macrohetero-
cycles of different ring size containing rigid and axially

G. Angelovski, P. Eilbracht / Tetrahedron 59 (2003) 8265–8274
8269
CH2Cl2/MeOH 97:3) to give 99 mg (64%) of 3a as a viscous
oil.
(100 MHz, CDCl3): d¼156.11, 140.96, 131.44, 128.30,
128.24, 120.24, 112.08, 11.52, 71.63, 19.21. IR (film,
~
NaCl), n [cm21]¼3072, 2911, 1442, 1228. EA: for
1H NMR (400 MHz, CDCl3): signals for a 1:1 mixture of
diastereomers: d¼7.21–7.17 (m, 8H), 7.16–7.13 (m, 2H),
6.82 (s, 2H), 6.81 (s, 2H), 4.06 (dd, J¼11.0, 4.5 Hz, 1H),
3.90 (dd, J¼11.0, 5.3 Hz, 1H), 3.78 (dd, J¼10.8, 8.3 Hz,
1H), 3.66 (dd, J¼10.8, 8.0 Hz, 1H), 3.56 (d, J¼4.0 Hz, 1H),
3.42 (d, J¼13.5 Hz, 1H), 3.21 (d, J¼13.5 Hz, 1H), 3.11 (d.
J¼13.5 Hz, 1H), 2.39–2.24 (m, 2H), 2.20–2.09 (m, 4H),
2.03–1.97 (m, 2H), 1.87–1.80 (m, 1H), 1.76–1.72 (m, 2H),
1.62–1.54 (m, 1H), 1.22–1.16 (m, 1H), 1.12–0.94 (m, 4H),
0.90–0.84 (m, 1H), 0.67 & 0.64 (two d, 1:1, J¼6.8 Hz, 6H).
13C NMR (100 MHz, CDCl3): signals for a 1:1 mixture of
diastereomers: d¼152.22, 140.12, 128.95 & 128.88, 127.98,
126.62, 116.15 & 115.95, 72.86 & 72.74, 59.00 & 58.88,
53.38 & 53.08, 50.90 & 50.73, 29.12 & 29.04, 29.06 &
C20H22O2 (294.40 g/mol) calcd: C: 81.6%, H: 7.5%,
found: C: 81.4%, H: 7.4%. MS (FAB): 294 [M]þ, 239,
154, 136.
4.1.4. Preparation of 10,15-dibenzyl-7,18-dimethyl-
6,7,8,9,10,11,12,13,14,15,16,17,18,19-tetradecahydro-
5,20-dioxa-10,15-diaza-dibenzo[a,c]cycloeicosene (4a).
2,20-Bis-(2-methyl-allyloxy)-biphenyl
0.22 mmol),
(1b)
N,N0-dibenzyl-butane-1,4-diamine
(66 mg,
(2a)
(65 mg, 0.24 mmol) and [Rh(acac)(CO)2] (3 mg, 12 mmol)
were dissolved in 40 ml of 1,4-dioxane and placed in the
autoclave. The autoclave was pressurised with 80 bar CO/
H2 (1:1) and heated at 808C for 3 days. After cooling solvent
was removed in a rotary evaporator and the crude mixture
was purified by column chromatography (silica gel, CH2Cl2/
MeOH 97:3) to give 90 mg (68%) of 4a as a viscous oil.
28.87, 25.84 & 25.69, 16.44 & 16.05. IR (film, NaCl), n
~
[cm21]¼2952, 2794, 1506, 1228, 1207. HRMS (FAB): for
C34H46N2O2 calcd: 513.3481 [M2H]þ, 515.3638 [MþH]þ;
found: 513.3469, 515.3612.
1H NMR (500 MHz, CDCl3): signals for a 1:1 mixture of
diastereomers: d¼7.22–7.12 (m, 14H), 6.89–6.81 (m, 4H),
3.93–3.51 (m, 4H), 3.49–3.27 (m, 4H), 2.29–2.16 (m, 8H),
1.84–1.77 (m, 2H), 1.49–1.41 (m, 2H), 1.38–1.22 (m, 4H),
1.16–1.04 (m, 2H), 0.67–0.55 (m, 6H). 13C NMR
(125 MHz, CDCl3): signals for a 1:1 mixture of dia-
stereomers: d¼156.80 & 156.66, 140.10 & 140.04 &
140.01, 131.67 & 131.32 & 131.09, 128.93 & 128.88
& 128.82, 128.60 & 128.57, 128.22 & 128.16 & 128.07 &
128.02, 126.67 & 126.59, 120.15 & 120.00, 119.87 &
119.43, 112.99 & 112.93 & 112.12 & 111.94, 73.83 & 73.50
& 73.32, 59.16 & 58.93 & 58.87, 53.36 & 53.20, 51.36 &
51.13 & 51.10 & 50.81, 31.39 & 31.33 & 31.18, 30.68 &
30.11, 25.12 & 24.86 & 24.69, 17.31 & 17.05 & 16.92
4.1.2. Preparation of 7,14-dibenzyl-4,17-dimethyl-2,19-
dioxa-7,14-diaza-bicyclo[18.2.2]tetracosa-1(23),
20(24),21-triene (3b). 1,4-Bis-(2-methyl-allyloxy)-benzene
(1a) (53 mg, 0.24 mmol), N,N0-dibenzyl-hexane-1,6-dia-
mine (2b)10b (72 mg, 0.24 mmol) and [Rh(acac)(CO)2]
(3 mg, 12 mmol) were dissolved in 40 ml of 1,4-dioxane and
placed in the autoclave. The autoclave was pressurised with
80 bar CO/H2 (1:1) and heated at 808C for 3 days. After
cooling the solvent was removed in a rotary evaporator and
the crude mixture was purified by column chromatography
(silica gel, CH2Cl2/MeOH 97:3) to give 78 mg (59%) of 3b
as a viscous oil.
& 16.82. IR (film, NaCl), n [cm21]¼2929, 2796, 1444,
~
1259, 1236. HRMS (FAB): for C40H50N2O2 calcd:
1H NMR (400 MHz, CDCl3): signals for a 1:1 mixture of
diastereomers: d¼7.20–7.18 (m, 8H), 7.15–7.11 (m, 2H),
6.79 (s, 4H), 3.87–3.77 (m, 4H), 3.46 (d, J¼5.0 Hz, 1H),
3.43 (d, J¼4.8 Hz, 1H), 3.31 (s, 1H), 3.28 (s, 1H), 2.40–
2.25 (m, 4H), 2.23–2.16 (m, 2H), 2.12–2.05 (m, 2H),
2.03–1.96 (m, 2H), 1.64–1.57 (m, 2H), 1.31–1.25 (m, 2H),
1.20–1.11 (m, 4H), 0.88–0.86 (m, 4H), 0.78 (two d, 1:1,
J¼6.8 Hz, 6H) 13C NMR (100 MHz, CDCl3): signals for a
1:1 mixture of diastereomers: d¼152.69, 152.62, 140.05,
128.91, 128.84, 127.99, 126.60, 115.63, 72.76, 72.70, 59.04,
58.98, 53.41, 53.34, 50.37, 29.90, 29.79, 29.52, 29.48,
591.3951 [MþH]þ, found: 591.3984.
4.1.5. Preparation of 10,17-dibenzyl-7,20-dimethyl-
6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21-hexadeca-
hydro-5,22-diox0a-10,17-diaza-dibenzo[a,c]cyclo-
docosene (4b). 2,2 -Bis-(2-methyl-allyloxy)-biphenyl (1b)
(162 mg, 0.55 mmol), N,N0-dibenzyl-hexane-1,6-diamine
(2b) (151 mg, 0.51 mmol) and [Rh(acac)(CO)2] (4 mg,
16 mmol) were dissolved in 40 ml of 1,4-dioxane and
placed in the autoclave. The autoclave was pressurised with
80 bar CO/H2 (1:1) and heated at 808C for 3 days. After
cooling solvent was removed in a rotary evaporator and the
crude mixture was purified by column chromatography
(silica gel, CH2Cl2/MeOH 97:3) to give 235 mg (75%) of 4b
as a viscous oil.
27.82, 27.77, 26.87, 17.15, 17.09. IR (film, NaCl), n
~
[cm21]¼2931, 2794, 1506, 1228, 1028. HRMS (FAB): for
C36H50N2O2 calcd: 543.3951 [MþH]þ; found: 543.3946.
4.1.3. Preparation of 2,20-bis-(methyl-allyloxy)-biphenyl
(1b). Biphenyl-2,20diol (6.02 g, 32.3 mmol) was added to a
stirred mixture of methylallyl chloride (7.6 g, 84.5 mmol)
and potassium carbonate (11.1 g, 80.5 mmol) in 50 ml of
acetone and heated under reflux for 2 days. After cooling
K2CO3 was removed by filtration and the acetone was
evaporated. The crude product was purified by column
chromatography (silica gel, cyclohexane/MTBE 9:1) to give
4.97 g (52%) of 1b as a yellow oil.
1H NMR (500 MHz, CDCl3): signals for a 1:1 mixture of
diastereomers: d¼7.19–7.10 (m, 14H), 6.81 (t, J¼7.2 Hz,
2H), 6.71 (t, J¼8.2 Hz, 2H), 3.57–3.50 (m, 4H), 3.32 (dd,
J¼22.9, 13.7 Hz, 4H), 2.26–2.17 (m, 8H), 1.71–1.66 (m,
2H), 1.30–1.23 (m, 4H), 1.09–1.03 (m, 8H), 0.67 (d,
J¼6.7 Hz, 6H). 13C NMR (125 MHz, CDCl3): signals for a
1:1 mixture of diastereomers: d¼156.75 & 156.61, 139.38
& 139.88, 131.55 & 131.46, 128.88, 128.64, 128.36, 128.13,
128.01 & 127.96, 126.62 & 126.57, 120.00 & 119.95 &
119.90, 112.64 & 112.36, 74.05 & 73.89 & 73.55 & 73.46,
58.94 & 58.85 & 58.76, 53.07 & 52.98 & 52.82, 51.13 &
1H NMR (400 MHz, CDCl3): d¼7.22–7.17 (m, 4H), 6.90
(dt, J¼6.8, 1.0 Hz, 2H), 6.83 (d, J¼8.3 Hz, 2H), 4.77 (d,
J¼26.1 Hz, 4H), 4.26 (s, 4H), 1.57 (s, 6H). 13C NMR

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G. Angelovski, P. Eilbracht / Tetrahedron 59 (2003) 8265–8274
50.96 & 50.90 & 50.87, 31.44 & 31.29 & 31.23 & 31.13,
30.95 & 30.91, 30.29, 26.69 & 26.65 & 26.51 & 26.45,
134.25 & 134.22, 129.29, & 129.24 & 129.92, 128.99 &
129.96, 128.89 & 128.86 & 128.82, 128.01 & 127.97,
127.73 & 127.70, 126.60 & 126.53, 125.94, 125.52 &
125.47, 123.34, 120.84 & 120.76 & 120.71, 116.02 &
115.92 & 115.85, 75.23 & 75.02 & 74.82 & 74.72, 58.87
& 58.75 & 58.66 & 58.61, 53.03 & 52.98 & 52.78, 50.99 &
50.88 & 50.74, 31.27 & 31.11 & 31.07 & 31.03, 30.63 &
30.50, 30.09, 26.88 & 26.76 & 26.64 & 26.48, 16.70 & 16.65
~
1506, 1456, 1263, 1242. HRMS (FAB): for C50H58N2O2
calcd: 719.4577 [MþH]þ; found: 719.4567.
4.1.8. Preparation of 3-methyl-4-[20-(2-methyl-4-oxo-
butoxy)-[1,10]binaphthalenyl-2-yloxy]-but0yraldehyde
(5c). (S)-(2)-2,20-Bis-(2-methyl-allyloxy)-[1,1 ]binaphthal-
enyl (3c) (135 mg, 0.34 mmol) and [Rh(acac)(CO)2] (4 mg,
16 mmol) were dissolved in 15 ml of toluene and placed in
the autoclave. Mixture was pressurised with 60 bar CO/H2
(1:1) and heated at 808C for 1 day. After cooling solvent was
removed in a rotary evaporator and the crude mixture was
purified by column chromatography (silica gel, CH2Cl2) to
give 114 mg (73%) of 5c as a colourless viscous oil.
17.09 & 17.02 & 16.85. IR (film, NaCl), n [cm21]¼2927,
~
2794, 1466, 1261. HRMS (FAB): for C42H54N2O2 calcd:
618.4185 [M]þ; found: 618.4172.
4.1.6. Preparation of 10,15-dibenzyl-7,18-dimethyl-
6,7,8,9,10,11,12,13,14,15,16,17,18,19-tetradecahydro-
5,20-dioxa-10,15-diaza-dinaphtho[a,c]cycloeicosene
(5a). (S)-(2)-2,20-Bis-(2-methyl-allyloxy)-[1,10]binaphthal-
enyl (3c)16 (153 mg, 0.39 mmol), N,N0-dibenzyl-butane-1,4-
diamine (2a) (100 mg, 0.37 mmol) and [Rh(acac)(CO)2]
(4 mg, 16 mmol) were dissolved in 40 ml of 1,4-dioxane and
placed in the autoclave. The autoclave was pressurised with
80 bar CO/H2 (1:1) and heated at 808C for 3 days. After
cooling solvent was removed in a rotary evaporator and the
crude mixture was purified by column chromatography
(silica gel, CH2Cl2/MeOH 97:3) to give 200 mg (78%) of 5a
as a viscous oil.
& 16.55. IR (film, NaCl), n [cm21]¼2927, 2794, 1591,
1H NMR (400 MHz, CDCl3): signals for a 1:1 mixture of
diastereomers: d¼7.85–7.71 (m, 4H), 7.35–7.07 (m, 18H),
3.94–3.85 (m, 2H), 3.64–3.51 (m, 2H), 3.48–3.15 (m, 4H),
2.23–2.13 (m, 4H), 2.07–1.95 (m, 4H), 1.71–1.59 (m, 2H),
1.37–1.01 (m, 8H), 0.39–0.27 (m, 6H). 13C NMR
(100 MHz, CDCl3): signals for a 1:1 mixture of dia-
stereomers: d¼154.75 & 154.63 & 154.40, 140.31 &
140.12, 134.25 & 134.21, 129.34 & 129.28, 129.10 &
129.06, 128.99 & 128.97 & 128.94, 128.87, 128.81
& 128.75, 128.01 & 127.97, 127.73 & 127.70, 126.60 &
126.59, 126.50, 125.96 & 125.93, 125.46 & 125.45 &
125.42, 123.38 & 123.24, 120.91 & 120.52 & 120.38,
116.24 & 116.17, 115.63 & 115.49, 74.88 & 74.69 & 74.62,
59.09 & 58.98 & 58.83 & 58.70, 53.44 & 53.16 & 53.13,
50.95 & 50.93 & 50.84 & 50.75, 31.19 & 31.11 & 31.09,
30.61 & 30.57, 29.98 & 29.89, 25.19 & 25.14 & 25.00 &
1H NMR (500 MHz, CDCl3), signals for a 1:1:2 mixture of 3
diastereomers: d¼9.04, 9.03 & 8.92 (three t, 1:1:2,
J¼1.7 Hz, 1H), 7.87 (d, J¼2.7 Hz, 1H), 7.85 (d,
J¼2.7 Hz, 1H), 7.77 (d, J¼8.2 Hz, 2H), 7.31–7.27 (m,
2H), 7.24 (t, J¼7.2 Hz, 2H), 7.16–7.08 (m, 4H), 3.87 (dd,
J¼8.7, 4.7 Hz, 1H), 3.82–3.78 (m, 1H), 3.69–3.66 (m, 1H),
3.59–3.54 (m, 1H), 2.11–1.99 (m, 2H), 1.86–1.79 (m, 2H),
1.70–1.61 (m, 2H), 0.60, 0.59 & 0.56 (three d, 1:1:2, J¼5.0,
5.0, 7.0 Hz, 6H). 13C NMR (125 MHz, CDCl3): signals for a
1:1:2 mixture of 3 diastereomers: d¼201.99 & 201.96 &
201.87, 154.00 & 153.91, 133.99, 129.32, 129.29, 127.84,
126.28, 125.32 & 125.29, 123.72 & 123.69, 120.50 &
120.47 & 120.38, 115.52 & 115.43 & 115.34 & 115.28,
73.64 & 73.60 & 73.55 & 73.52, 47.30 & 47.16, 28.36 &
24.72, 16.78 & 16.69 & 16.48. IR (film, NaCl), n
~
[cm21]¼2951, 2796, 1508, 1456, 1265, 1244. HRMS
(FAB): for C48H54N2O2 calcd: 691.4264 [MþH]þ, found:
691.4294.
28.33, 16.62 & 16.47. IR (film, NaCl), n [cm21] 2960, 1722,
~
1591, 1506, 1271, 1242. HRMS (FAB): for C30H30O4 calcd:
454.2144 [M]þ; found: 454.2155.
4.1.7. Preparation of 10,17-dibenzyl-7,20-dimethyl-
6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21-hexadeca-
hydro-5,22-dioxa-10,17-diaza-dinaphtho[a,c]cyclodoc0o-
sene (5b). (S)-(2)-2,20-Bis-(2-methyl-allyloxy)-[1,1 ]-
binaphthalenyl (3c) (150 mg, 0.38 mmol), N,N0-dibenzyl-
hexane-1,6-diamine (2b) (113 mg, 0.38 mmol) and
[Rh(acac)(CO)2] (4 mg, 16 mmol) were dissolved in 40 ml
of 1,4-dioxane and placed in the autoclave. The autoclave
was pressurised with 80 bar CO/H2 (1:1) and heated at 808C
for 3 days. After cooling solvent was removed in a rotary
evaporator and the crude mixture was purified by column
chromatography (silica gel, CH2Cl2/MeOH 97:3) to give
213 mg (78%) of 5b as a viscous oil.
4.1.9. Preparation of 4-[4-(4-oxo-butoxy)-phenoxy]-
butyraldehyde (7a). 1,4-Bis-allyloxy-benzene (6a)15b
(500 mg, 2.63 mmol), [Rh(acac)(CO)2] (5 mg, 19 mmol),
XANTPHOS (50 mg, 86 mmol) and toluene (15 ml) were
dissolved in the autoclave. The solution was pressurised
with 20 bar CO/H2 (1:1) and heated at 708C for 18 h. The
solvent was removed in a rotary evaporator and the crude
mixture was purified by column chromatography (silica gel,
Et2O/n-hexane 1:1) to give 515 mg (78%) of 7a as a white
solid.
1H NMR (400 MHz, CDCl3): d¼9.77 (s, 2H), 6.73 (s, 4H),
3.88 (t, J¼6.0 Hz, 4H), 2.59 (dt, J¼5.7, 1.2 Hz, 4H), 2.04–
2.01 (m, 4H). 13C NMR (100 MHz, CDCl3): d¼201.95,
1H NMR (400 MHz, CDCl3): signals for a 1:1 mixture of
diastereomers: d¼7.82–7.74 (m, 4H), 7.33–7.28 (m, 2H),
7.21–7.12 (m, 16H), 3.84–3.76 (m, 2H), 3.63–3.56 (m,
1H), 3.49–3.41 (m, 1H), 3.36–3.28 (m, 3H), 3.21–3.15
(m, 1H), 2.26–2.14 (m, 4H), 2.09–2.01 (m, 4H), 1.69–1.54
(m, 2H), 1.32–0.95 (m, 12H), 0.35 & 0.29 (two m, 1:1, 3H).
13C NMR (100 MHz, CDCl3): signals for a 1:1 mixture of
diastereomers: d¼154.63, 154.55 & 154.52, 140.20, 139.95,
152.88, 115.32, 67.21, 40.60, 22.03. IR (disk, KBr), n
~
[cm21]¼2951, 2833, 2727, 1714, 1512, 1238. EA: for
C14H18O4 (250.29 g/mol) calcd: C: 67.2%, H: 7.2%, found:
C: 66.7%, H: 7.2%. HRMS (EI): calcd: 250.1205 [M]þ;
found: 250.1196. Mp: 498C.
4.1.10. Preparation of 4-[20-(4-ox0o-butoxy)-biphenyl-2-
yloxy]-butyraldehyde (7b). 2,2 -Bis-allyloxy-biphenyl

G. Angelovski, P. Eilbracht / Tetrahedron 59 (2003) 8265–8274
8271
(6b)17 (586 mg, 2.20 mmol), [Rh(acac)(CO)2] (4 mg,
16 mmol), XANTPHOS (41 mg, 71 mmol) and toluene
(15 ml) were dissolved in the autoclave. The solution was
pressurised with 20 bar CO/H2 (1:1) and heated at 708C for
18 h. The solvent was removed in a rotary evaporator and
the crude mixture was purified by column chromatography
(silica gel, Et2O/n-hexane 1:1) to give 451 mg (63%) of 7b
as a colourless viscous oil.
126.67 & 126.60, 116.58 & 115.42 & 115.30, 68.34 & 68.32
& 67.86, 58.92 & 58.85, 53.54 & 53.47, 53.23 & 53.12 &
~
2796, 1506, 1228. HRMS (FAB): for C32H42N2O2 calcd:
487.3325 [MþH]þ; found: 487.3341.
53.05, 26.17, 25.67, 21.90. IR (film, NaCl), n [cm21]¼2943,
4.1.13. Preparation of 7,14-dibenzyl-2,19-dioxa-7,14-
diaza-bicyclo[18.2.2]tetracosa-1(23),20(24),21-triene
(8b). 4-[4-(4-Oxo-butoxy)-phenoxy]-butyraldehyde (7a)
(104 mg, 0.42 mmol), N,N0-dibenzyl-hexane-1,6-diamine
(2b) (126 mg, 0.42 mmol) and [Rh(acac)(CO)2] (4 mg,
16 mmol) were mixed in 40 ml of toluene and stirred for
1 hour. The solution was placed in the autoclave,
pressurised with 50 bar hydrogen and heated at 508C for 2
days. The solvent was removed in a rotary evaporator and
the crude product was purified by column chromatography
(silica gel, CH2Cl2/MeOH 97:3) to give 103 mg (48%) of 8b
as a white amorphous solid.
1H NMR (400 MHz, CDCl3): d¼9.46 (s, 2H), 7.23 (dt,
J¼6.5, 1.5 Hz, 2H), 7.14 (dd, J¼5.8, 1.8 Hz, 2H), 6.94 (dt,
J¼6.3, 1.0 Hz, 2H), 6.87 (d, J¼8.3 Hz, 2H), 3.87 (t,
J¼5.8 Hz, 4H), 2.29 (dt, J¼5.8, 1.2 Hz, 4H), 1.88–1.82
(m, 4H). 13C NMR (100 MHz, CDCl3): d¼202.05, 156.14,
131.32, 128.52, 128.45, 120.62, 110.57, 67.39, 40.35, 22.00.
IR (film, NaCl), n [cm21]¼2937, 1722, 1441, 1234. EA: for
~
C20H22O4 (326.40 g/mol) calcd: C: 73.6%, H: 6.8%, found:
C: 73.3%, H: 6.9%. MS (EI): 326 [M]þ, 256, 228, 212, 197.
4.1.11. Preparation of (R)-(1)-4-[20-(4-oxo-butoxy)-
[1,10]binaphtalenyl-2-ylo0xy]-butyraldehyde (7c). (R)-
(þ)-2,20-Bis-allyloxy-[1,1 ]binaphthalenyl (6c)16 (412 mg,
1H NMR (400 MHz, CDCl3): d¼7.22–7.12 (m, 10H), 6.81
(s, 4H), 4.02 (t, J¼6.0 Hz, 4H), 3.38 (s, 4H), 2.31 (t,
J¼6.3 Hz, 4H), 2.16 (t, J¼7.3 Hz, 4H), 1.69–1.64 (m, 4H),
1.57–1.52 (m, 4H), 1.22–1.12 (m, 4H), 0.93–0.87 (m, 4H).
13C NMR (100 MHz, CDCl3): d¼152.61, 140.18, 128.80,
128.02, 126.59, 115.97, 67.85, 59.06, 53.42, 52.44, 27.85,
1.12 mmol),
[Rh(acac)(CO)2]
(3 mg,
12 mmol),
XANTPHOS (30 mg, 52 mmol) and toluene (15 ml) were
dissolved in the autoclave. The solution was pressurised
with 20 bar CO/H2 (1:1) and heated on 708C for 18 h. The
solvent was removed in a rotary evaporator and the crude
mixture was purified by column chromatography (silica gel,
toluene/EtOAc 9:1) to give 384 mg (80%) of 7c as a
colourless viscous oil.
26.22, 22.06. IR (disk, KBr), n [cm21]¼2931, 2794, 1506,
~
1228. EA: for C34H46N2O2 (514.74 g/mol) calcd: C: 79.3%,
H: 9.0%, N: 5.4%, found: C: 79.0%, H: 8.8%, N: 5.4%.
HRMS (FAB): calcd: 515.3638 [MþH]þ; found: 515.3636.
4.1.14. Preparation of 10,15-dibenzyl-6,7,8,9,10,
11,12,13,14,15,16,17,18,19-tetradecahydro-5,20-dioxa-
10,15-diaza-dibenzo[a,c]cycloeicosene (9a). 4-[20-(4-Oxo-
butoxy)-biphenyl-2-yloxy]-butyraldehyde (7b) (42 mg,
1H NMR (400 MHz, CDCl3): d¼9.05 (s, 2H), 7.88 (t,
J¼9.0 Hz, 2H), 7.80 (d, J¼8.2 Hz, 2H), 7.33 (d, J¼9.0 Hz,
2H), 7.27 (t, J¼8.0 Hz, 2H), 7.16 (dt, J¼5.7, 1.0 Hz, 2H),
4.00–3.96 (m, 2H), 3.85–3.81 (m, 2H), 1.85–1.72 (m, 4H),
1.66–1.58 (m, 4H). 13C NMR (100 MHz, CDCl3):
d¼201.78, 153.93, 131.89, 129.32, 129.26, 127.84,
126.27, 125.20, 123.71, 120.58, 115.75, 68.42, 39.70,
~
1506, 1263. HRMS (EI): for C28H26O4 calcd: 426.1831
[M]þ; found: 426.1816. [a]D20¼292.9 (c¼0.8, CH2Cl2).
0.13 mmol),
N,N0-dibenzyl-butane-1,4-diamine
(2a)
(45 mg, 0.17 mmol) and [Rh(acac)(CO)2] (3 mg, 12 mmol)
were mixed in 40 ml of toluene and stirred for 1 hour. The
solution was placed in the autoclave, pressurised with 60 bar
hydrogen and heated at 708C for 2 days. The solvent was
removed in a rotary evaporator and the crude product was
purified by column chromatography (silica gel, CH2Cl2/
MeOH 97:3) to give 31 mg (43%) of 9a as a colourless
viscous oil.
21.75. IR (film, NaCl), n [cm21]¼2937, 1722, 1591,
4.1.12. Preparation of 7,12-dibenzyl-2,17-dioxa-7,12-
diaza-bicyclo[16.2.2]docosa-1(21)18(22),19-triene (8a).
4-[4-(4-Oxo-butoxy)-phenoxy]-butyraldehyde (7a) (136 mg,
0.54 mmol), N,N0-dibenzyl-butane-1,4-diamine(2a) (160 mg,
0.60 mmol) and [Rh(acac)(CO)2] (4 mg, 16 mmol) were
mixed in 40 ml of toluene and stirred for 1 hour. The solution
was placed in the autoclave, pressurised with 60 bar hydrogen
and heated at 708C for 2 days. The solvent was removed in a
rotary evaporator and the crude product was purified by
column chromatography (silica gel, CH2Cl2/MeOH 97:3) to
give 137 mg (52%) of 8a as a colourless viscous oil.
1H NMR (500 MHz, CDCl3): d¼7.23–7.12 (m, 14H),
6.92–6.85 (m, 4H), 3.89–3.80 (m, 4H), 3.47–3.33 (dd,
J¼58.3, 13.7 Hz, 4H), 2.32–2.21 (m, 8H), 1.71–1.61 (m,
2H), 1.58–1.49 (m, 2H), 1.39–1.37 (m, 8H). 13C NMR
(125 MHz, CDCl3): d¼156.81, 131.15, 128.96, 128.79,
128.31, 128.04, 126.62, 120.24, 112.27, 68.65, 59.25, 53.34,
27.27, 24.95, 23.53. IR (film, NaCl), n [cm21]¼2960, 2796,
~
1593, 1261, 1026. HRMS (FAB): for C38H46N2O2 calcd:
563.3638 [MþH]þ; found: 563.3665.
1H NMR (400 MHz, CDCl3): signals for a 2:1 mixture of
two stereoisomeric forms: d¼7.22–7.13 (m, 10H), 6.83 &
6.67 (two s, 1:2, 4H), 4.08 & 3.79–3.74 (t and m, 1:2,
J¼5.8 Hz, 4H), 3.45 & 3.35 (two s, 2:1, 4H), 2.38–2.35 &
2.33–2.30 & 2.22 (two m and t, J¼6.5 Hz, 8H), 2.06–1.99
(m, 4H), 1.70–1.63 & 1.61–1.53 & 1.39–1.37 (three m,
8H). 13C NMR (100 MHz, CDCl3): signals for a 2:1 mixture
of two stereoisomeric forms: d¼153.07 & 152.18, 140.05 &
139.95 & 139.91, 128.85 & 128.74, 128.08 & 128.02,
4.1.15. Preparation of 10,17-dibenzyl-6,7,8,9,10,
11,12,13,14,15,16,17,18,19,20,21-hexadecahydro-5,22-
dioxa-10,17-diaza-dibenzo[a,c]cyclodocosene (9b). 4-[20-
(4-Oxo-butoxy)-biphenyl-2-yloxy]-butyraldehyde
(7b)
(48 mg, 0.15 mmol), N,N0-dibenzyl-hexane-1,6-diamine
(2b) (44 mg, 0.15 mmol) and [Rh(acac)(CO)2] (3 mg,
12 mmol) were mixed in 40 ml of toluene and stirred for
1 h. The solution was placed in the autoclave, pressurised
with 60 bar hydrogen and heated at 708C for 2 days. The

8272
G. Angelovski, P. Eilbracht / Tetrahedron 59 (2003) 8265–8274
solvent was removed in a rotary evaporator and the crude
product was purified by column chromatography (silica gel,
CH2Cl2/MeOH 97:3) to give 25 mg (29%) of 9b as a
colourless viscous oil.
J¼23.1, 13.8 Hz, 4H), 2.20 (t, J¼6.5 Hz, 4H), 2.15–2.04
(m, 4H), 1.44–1.31 (m, 8H), 1.23–1.20 (m, 4H), 1.17–1.10
(m, 4H). 13C NMR (100 MHz, CDCl3): d¼154.66, 140.19,
134.18, 129.29, 129.06, 128.77, 127.99, 127.77, 126.55,
126.03, 125.46, 123.40, 120.79, 116.25, 70.04, 58.84, 52.91,
1H NMR (400 MHz, CDCl3): d¼7.22–7.12 (m, 14H),
6.92–6.82 (m, 4H), 3.82 (t, J¼6.5 Hz, 4H), 3.40 (s, 4H),
2.28–2.22 (m, 8H), 1.59–1.54 (m, 4H), 1.41–1.33 (m, 8H),
1.24–1.18 (m, 4H). 13C NMR (100 MHz, CDCl3):
d¼156.76, 140.18, 131.17, 128.84, 128.79, 128.28,
128.02, 126.59, 120.24, 112.37, 68.68, 59.08, 53.09,
52.78, 27.26, 26.58, 26.39, 23.20. IR (film, NaCl), n
~
[cm21]¼2929, 2794, 1508, 1454, 1263, 1085. HRMS
(FAB): for C48H54N2O2 calcd: 691.4264 [MþH]þ,
713.4083 [MþNa]þ; found: 691.4250, 713.4091.
[a]2D0¼265.4 (c¼0.44, CH2Cl2).
27.33, 26.44, 26.29, 23.70. IR (film, NaCl),
n
4.1.18. Preparation of 1,4-bis-pent-4-enyloxy-benzene
(11a). Potassium hydroxide (3.08 g, 54.9 mmol) was
dissolved in absolute ethanol (200 ml) at room temperature.
To this stirred solution were added hydroquinone (2.00 g,
18.2 mmol) and 5-bromo-pent-1-ene (8.12 g, 54.5 mmol).
The solution was heated at 808C and allowed to stir for 24 h.
After being cooled to a room temperature, the mixture was
diluted with water and CH2Cl2, and the layers were
separated. The aqueous phase was further extracted with
CH2Cl2, and combined organic layers were dried over
MgSO4, filtered and concentrated. The residue was purified
by column chromatography (silica gel, CH2Cl2) to give
3.81 g (85%) of 11a as a white solid.
~
[cm21]¼2935, 2794, 1504, 1442, 1261. HRMS (FAB): for
C40H50N2O2 calcd: 591.3951 [MþH]þ; found: 591.3922.
4.1.16. Preparation of 10,15-dibenzyl-6,7,8,9,10,
11,12,13,14,15,16,17,18,19-tetradecahydro-5,20-dioxa-
10,15-diaza-dinaphtho[a,c]cycloeicosene (10a). 4-[20-(4-
Oxo-butoxy)-[1,10]binaphthalenyl-2-yloxy]-butyraldehyde
(7c) (50 mg, 0.12 mmol), N,N0-dibenzyl-butane-1,4-dia-
mine (2a) (33 mg, 0.12 mmol) and [Rh(acac)(CO)2]
(3 mg, 12 mmol) were mixed in 40 ml of toluene and stirred
for 1 h. The solution was placed in the autoclave,
pressurised with 50 bar hydrogen and heated at 608C for 1
day. The solvent was removed in a rotary evaporator and the
crude product was purified by column chromatography
(silica gel, CH2Cl2/MeOH 97:3) to give 39 mg (50%) of 10a
as a colourless viscous oil.
1H NMR (500 MHz, CDCl3): d¼6.74 (s, 4H), 5.82–5.74
(m, 2H), 4.98 (dd, J¼17.2, 1.7 Hz, 2H), 4.92 (d, J¼9.5 Hz,
2H), 3.84 (t, J¼6.5 Hz, 4H), 2.18–2.13 (m, 4H), 1.81–1.75
(m, 4H). 13C NMR (125 MHz, CDCl3): d¼153.15, 137.90,
1H NMR (500 MHz, CDCl3): signals for a 2:1 mixture of
two stereoisomeric forms: d¼7.86 (dd, J¼14.2, 9.0 Hz, 2H),
7.77 (d, J¼8.0 Hz, 2H), 7.34 (dd, J¼9.0, 1.7 Hz, 2H), 7.24–
7.05 (m, 16H), 4.16–4.12 & 3.95–3.91 (two m, 1:2, 2H),
3.86–3.82 & 3.81–3.77 (two m, 1:2, 2H), 3.54–3.50 & 3.33
& 3.30–3.28 (two m and s, 1:2:1, 4H), 2.44–2.36 (m, 1H),
2.23–2.10 (m, 7H), 1.50–1.41 (m, 5H), 1.34–1.31 (m, 3H),
1.20–1.13 (m, 4H). 13C NMR (125 MHz, CDCl3): signals
for a 2:1 mixture of two stereoisomeric forms: d¼154.63 &
154.02, 140.16, 134.21, 129.26, 129.05, 128.88 & 128.85,
128.76, 128.04 & 127.99, 127.77 & 127.73, 126.67 & 126.57,
126.07 & 126.03, 125.43 & 125.26, 123.38 & 123.03, 120.68,
116.13 & 113.83, 69.81 & 66.74, 59.02, 53.17 & 52.84, 51.31,
115.40, 115.07, 67.81, 30.11, 28.52. IR (disk, KBr), n
~
[cm21]¼2939, 2868, 1510, 1057. EA: for C16H22O2
(246.35 g/mol) calcd: C: 78.0%, H: 9.0%, found: C:
78.2%, H: 9.1%. MS (FAB): 246 [M]þ, 191, 178, 123,
110, 70. Mp: 34–368C.
4.1.19. Preparation of S-(1)-2,20-bis-hex-5-enyloxy-
[1,100]binaphthalenyl (11b). To a solution of S(þ)-
[1,1 ]binaphthalenyl-2,20-diol (3.03 g, 10.6 mmol) in THF
(30 ml) were added 5-hexen-1-ol (3.47 g, 34.6 mmol) and
triphenylphosphine (6.88 g, 26.2 mmol) at room tempera-
ture. Diisopropyl azodicarboxylate (5.30 g, 26.2 mmol) was
then added dropwise. The reaction mixture was stirred at
room temperature for 24 h. The solution was decanted, and
solids were washed several times with hexanes. The organic
solutions were combined and concentrated. The residue was
purified by column chromatography (silica gel, CH2Cl2/
n-hexane 4:1) to give 4.14 g (87%) of 11b as a yellow oil.
27.23 & 26.52, 24.89, 23.12. IR (film, NaCl), n [cm21]¼2944,
~
2796, 1508, 1263. HRMS (FAB): for C46H50N2O2 calcd:
663.3951 [MþH]þ; found: 663.3981.
4.1.17. Preparation of (R)-(1)-10,17-dibenzyl-6,7,8,
9,10,11,12,13,14,15,16,17,18,19,20,21-hexadecahydro-
5,22-dioxa-10,17-diaza-dinaphtho[a,c0]cyclodocosene
(10b). (R)-(2)-4-[20-(4-Oxo-butoxy)-[1,1 ]binaphthalenyl-
2-yloxy]-butyraldehyde (7c) (115 mg, 0.27 mmol), N,N0-
dibenzyl-hexane-1,6-diamine (2b) (83 mg, 0.28 mmol) and
[Rh(acac)(CO)2] (3 mg, 12 mmol) were mixed in 40 ml of
toluene and stirred for 1 h. The solution was placed in the
autoclave, pressurised with 50 bar hydrogen and heated at
658C for 2 days. The solvent was removed in a rotary
evaporator and the crude product was purified by column
chromatography (silica gel, CH2Cl2/MeOH 97:3) to give
132 mg (71%) of 10b as a colourless viscous oil.
1H NMR (500 MHz, CDCl3): d¼7.87 (d, J¼9.0 Hz, 2H),
7.80 (d, J¼8.0 Hz, 2H), 7.35 (d, J¼9.0 Hz, 2H), 7.35 (t,
J¼6.5 Hz, 2H), 7.17–7.11 (m, 4H), 5.53–5.45 (m, 2H),
4.79–4.73 (m, 2H), 3.94–3.84 (m, 4H), 1.71–1.67 (m, 4H),
1.40–1.33 (m, 4H), 1.00–0.94 (m, 4H). 13C NMR
(125 MHz, CDCl3): d¼154.45, 138.66, 134.19, 129.26,
129.05, 127.77, 126.04, 125.46, 123.40, 120.68, 115.78,
114.15, 69.48, 33.04, 28.74, 24.78. IR (film, NaCl), n
~
[cm21]¼2935, 1591, 1508, 1271, 1242. EA: for C32H34O2
(246.35 g/mol) calcd: C: 85.3%, H: 7.6%, found: C: 85.5%,
H: 7.4%. MS (FAB): 450 [M]þ, 368, 286, 269. [a]2D0¼þ75.3
(c¼0.6, CH2Cl2).
1H NMR (400 MHz, CDCl3): d¼7.83 (d, J¼9.0 Hz, 2H),
7.76 (d, J¼8.3 Hz, 2H), 7.32 (d, J¼9.0 Hz, 2H), 7.24–7.06
(m, 16H), 3.91–3.85 (m, 2H), 3.83–3.77 (m, 2H), 3.32 (dd,
4.1.20. Preparation of 6-[4-(6-oxo-hexyloxy)-phenoxy]-
hexanal (12a). 1,4-Bis-pent-4-enyloxy-benzene (11a)

G. Angelovski, P. Eilbracht / Tetrahedron 59 (2003) 8265–8274
8273
(200 mg, 0.81 mmol), [Rh(acac)(CO)2] (3 mg, 12 mmol),
XANTPHOS (29 mg, 50 mmol) and toluene (15 ml) were
dissolved in the autoclave. The solution was pressurised
with 80 bar CO/H2 (1:1) and heated at 1208C for 18 h.
Solvent was removed in a rotary evaporator and the crude
mixture was purified by column chromatography (silica gel,
Et2O/n-hexane 3:2) to give 0.183 g (74%) of 12a as a white
solid.
stereoisomeric forms: d¼153.12 & 152.87, 140.27 &
140.23, 128.78, 128.02 & 128.01, 126.58 & 126.54,
116.05 & 115.33, 68.49 & 68.30, 58.76, 53.75, 53.31,
28.13, 27.53 & 27.48, 26.98, 26.56 & 26.14, 25.16. IR (film,
NaCl), n [cm21]¼2933, 2792, 1506, 1228. HRMS (FAB):
~
for C38H54N2O2 calcd: 570.4185 [M]þ; found: 570.4186.
4.2. Preparation of S-(1)-13,18-dibenzyl-6,7,8,9,10,11,
12,13,14,15,16,17,18,19,20,21,22,23,24,25-eicosahydro-
5,26-dioxa-13,18-diaza-dinaphtho[a,c]cyclohexacosene
(13b)
1H NMR (400 MHz, CDCl3): d¼9.70 (s, 2H), 6.73 (s, 4H),
3.83 (t, J¼6.3 Hz, 4H), 2.39 (dt, J¼7.3, 1.5 Hz, 4H), 1.73–
1.66 (m, 4H), 1.66–1.58 (m, 4H), 1.46–1.39 (m, 4H). 13C
NMR (100 MHz, CDCl3): d¼202.47, 153.02, 115.28,
S-(þ)-7-[20-(7-Oxo-heptyloxy)-[1,10]binaphthalenyl-2-
yloxy]-heptanal (12b) (55 mg, 0.11 mmol), N,N0-dibenzyl-
butane-1,4-diamine (2a) (27 mg, 0.10 mmol) and
[Rh(acac)(CO)2] (4 mg, 16 mmol) were dissolved in 30 ml
of toluene and stirred for 1 h. The solution was placed in the
autoclave, pressurised with 40 bar hydrogen and heated at
508C for 1 day. The solvent was removed in a rotary
evaporator and the crude product was purified by column
chromatography (silica gel, CH2Cl2/MeOH 97:3) to give
58 mg (77%) of 13b as a yellow viscous oil.
68.08, 43.71, 29.05, 25.62, 21.73. IR (disk, KBr), n
~
[cm21]¼2943, 2729, 1712, 1510, 1227. EA: for C18H26O4
(306.40 g/mol) calcd: C: 70.6%, H: 8.6%, found: C: 70.3%,
H: 8.7%. HRMS (EI): calcd: 306.1831 [M]þ; found:
306.1825. Mp: 42–448C.
4.1.21. Preparation of S-(1)-7-[20-(7-oxo-heptyl0oxy)-
[1,10]binaphthalen0yl-2-yloxy]-heptanal (12b). 2,2 -Bis-
hex-5-enyloxy-[1,1 ]binaphthalenyl
(11b)
(212 mg,
0.47 mmol), [Rh(acac)(CO)2] (3 mg, 12 mmol), XANT-
PHOS (31 mg, 53 mmol) and toluene (15 ml) were dis-
solved in the autoclave. The solution was pressurised with
60 bar CO/H2 (1:1) and heated at 1008C for 18 h. Solvent
was removed in a rotary evaporator and the crude mixture
was purified by column chromatography (silica gel,
CH2Cl2) to give 0.139 g (58%) of 12b as a yellow oil.
1H NMR (500 MHz, CDCl3): d¼7.85–7.74 (m, 4H), 7.35–
7.02 (m, 18H), 3.86–3.80 (m, 4H), 3.42–3.38 (m, 4H),
2.27–2.22 (m, 8H), 1.42–1.26 (m, 12H), 1.21–1.18 (m,
2H), 1.13–1.07 (m, 6H), 1.04–1.01 (m, 4H). 13C NMR
(125 MHz, CDCl3): d¼154.57, 154.51, 140.34, 134.24,
129.17, 129.00, 128.79, 128.01, 127.75, 126.57, 126.04,
125.43 & 125.40, 123.31, 120.55, 120.47, 115.75, 69.77 &
69.63, 59.19 & 59.11, 53.69 & 53.46 & 53.42, 52.76, 29.35,
29.09, 28.55, 27.24 & 27.40, 26.72 & 26.56, 25.70, 25.41,
1H NMR (500 MHz, CDCl3): d¼9.56 (s, 2H), 7.83 (d,
J¼9.0 Hz, 2H), 7.75 (d, J¼8.2 Hz, 2H), 7.31 (d, J¼9.0 Hz,
2H), 7.21 (dt, J¼7.7, 1.2 Hz, 2H), 7.12–7.05 (m, 4H),
3.91–3.87 (m, 2H), 3.81–3.77 (m, 2H), 2.05 (dt, J¼7.5,
1.7 Hz, 4H), 1.33–1.26 (m, 4H), 1.23–1.16 (m, 4H), 0.91–
0.86 (m, 4H), 0.80–0.74 (m, 4H). 13C NMR (125 MHz,
CDCl3): d¼202.80, 154.41, 134.13, 129.23, 129.00, 127.72,
125.99, 125.41, 123.40, 120.68, 115.81, 69.51, 43.47, 29.01,
24.88. IR (film, NaCl), n [cm21]¼2941, 1593, 1508, 1271,
~
1088. HRMS (FAB): for C52H62N2O2 calcd: 747.5290
[MþH]þ; found: 747.4899. [a]D20¼þ82.1 (c¼0.7, CH2Cl2).
4.3. Preparation of S-(1)-13,18-dibenzyl-6,7,8,9,10,11,
12,13,14,15,16,17,18,19,20,21,22,23,24,25-eicosahydro-
5,26-dioxa-13,18-diaza-dinaphtho[a,c]cyclohexacosene
(13c)
28.33, 25.20, 21.64. IR (film, NaCl), n [cm21]¼2933, 1722,
~
1591, 1508, 1263. HRMS (EI): for C34H38O4 calcd:
510.2770 [M]þ; found: 510.2767. [a]2D0¼þ48.4 (c¼0.58,
CH2Cl2).
S-(þ)-7-[20-(7-Oxo-heptyloxy)-[1,10]binaphthalenyl-2-
yloxy]-heptanal (12b) (49 mg, 0.10 mmol), N,N0-dibenzyl-
hexane-1,4-diamine (2b) (34 mg, 0.11 mmol) and
[Rh(acac)(CO)2] (3 mg, 12 mmol) were dissolved in 30 ml
of toluene and stirred for 1 h. The solution was placed in the
autoclave, pressurised with 50 bar hydrogen and heated at
608C for 1 day. The solvent was removed in a rotary
evaporator and the crude product was purified by column
chromatography (silica gel, CH2Cl2/MeOH 97:3) to give
58 mg (78%) of 13c as a yellow viscous oil.
4.1.22. Preparation of 9,16-dibenzyl-2,23-dioxa-9,16-
diaza-bicyclo[22.2.2]octacosa-1(27),24(28),25-triene
(13a). 6-[4-(6-Oxo-hexylo0xy)-phenoxy]-hexanal (12a)
(53 mg, 0.17 mmol), N,N -dibenzyl-hexane-1,6-diamine
(2b) (59 mg, 0.2 mmol) and [Rh(acac)(CO)2] (3 mg,
12 mmol) were dissolved in 20 ml of toluene and stirred
for 1 h. The solution was placed in the autoclave,
pressurised with 40 bar hydrogen and heated at 508C for 1
day. The solvent was removed in a rotary evaporator and the
crude product was purified by column chromatography
(silica gel, CH2Cl2/MeOH 97:3) to give 52 mg (53%) of 13a
as a yellow viscous oil.
1H NMR (500 MHz, CDCl3): d¼7.81 (d, J¼9.0 Hz, 2H),
7.74 (d, J¼8.2 Hz, 2H), 7.30 (d, J¼9.0 Hz, 2H), 7.24–7.18
(m, 10H), 7.14–7.08 (m, 4H), 7.06–7.03 (m, 2H), 3.88–
3.80 (m, 4H), 3.43 (d, J¼2.2 Hz, 4H), 2.30–2.24 (m, 8H),
1.38–1.34 (m, 8H), 1.32–1.26 (m, 4H), 1.23–1.21 (m, 4H),
1.09–1.07 (m, 4H), 0.99–0.97 (m, 8H). 13C NMR
(125 MHz, CDCl3): d¼154.49, 140.33, 134.24, 129.18,
129.00, 128.79, 128.02, 127.75, 126.57, 126.03, 125.45,
123.31, 120.59, 115.74, 69.58, 59.07, 53.45, 53.34, 29.27,
1H NMR (400 MHz, CDCl3): signals for a 2:1 mixture of
two stereoisomeric forms: d¼7.25–7.18 (m, 10H), 6.78 &
6.72 (two s, 2:1, 4H), 3.94 & 3.79 (two t, 2:1, J¼6.5 Hz,
4H), 3.45 & 3.40 (two s, 2:1, 4H), 2.33–2.25 & 2.20 (m and
t, 2:1, J¼7.0 Hz, 8H), 1.69–1.62 (m, 4H), 1.44–1.23 (m,
16H), 1.18–1.15 & 1.08–1.05 (two m, 1:2, 4H). 13C NMR
(100 MHz, CDCl3): signals for a 2:1 mixture of two
28.95, 27.17, 27.04, 26.94, 26.88, 25.59. IR (film, NaCl), n
~
[cm21]¼2931, 2794, 1593, 1508, 1263. HRMS (FAB): for

8274
G. Angelovski, P. Eilbracht / Tetrahedron 59 (2003) 8265–8274
C54H66N2O2 calcd: 774.5124 [M]þ; found: 774.5118.
5. Richman, J. E.; Atkins, T. J. J. Am. Chem. Soc. 1974, 96,
2268–2270.
[a]2D0¼þ54.3 (c¼0.88, CH2Cl2).
6. (a) Armstrong, L. G.; Lindoy, L. F. Inorg. Chem. 1975, 14,
1322–1326. (b) Lindoy, L. F.; Lip, H. C.; Power, L. F.; Rea,
J. H. Inorg. Chem. 1976, 15, 1724–1727. (c) Armstrong, L. G.;
Grimsley, P. G.; Lindoy, L. F.; Lip, H. C.; Norris, V. A.;
Smith, R. J. Inorg. Chem. 1978, 17, 2350–2352.
4.4. Preparation of 2,23-dioxa-9,16-diaza-bicyclo-
[22.2.2]octacosa-1(27),24(28),25-triene (14)
9,16-Dibenzyl-2,23-dioxa-9,16-diaza-bicyclo[22.2.2]octa-
cosa-1(27),24(28),25-triene (13a) (114 mg, 0.20 mmol),
palladium on charcoal (150 mg, 10% Pd) and ethanol
(100 ml) were stirred under hydrogen (1 bar) for 24 h. After
removal of palladium by filtration, the solvent was removed
in a rotary evaporator to give 75 mg (96%) of 14 as a yellow
viscous oil.
¨
7. Eilbracht, P.; Barfacker, L.; Buss, C.; Hollmann, C.; Kitsos-
Rzychon, B. E.; Kranemann, C. L.; Rische, T.; Roggenbuck,
R.; Schmidt, A. Chem. Rev. 1999, 99, 3329–3365.
8. (a) Kranemann, C. L.; Eilbracht, P. Eur. J. Org. Chem. 2000,
2367–2377. (b) Kranemann, C. L.; Costisella, B.; Eilbracht, P.
Tetrahedron Lett. 1999, 40, 7773–7776.
9. Pruett, R. L. Adv. Organomet. Chem. 1979, 17, 1–60.
10. (a) Devinsky, F.; Lacko, I.; Krasnec, L. Synthesis 1980,
303–305. (b) Bhuniya, D.; Singh, V. K. Synth. Commun. 1994,
24, 375–385.
1H NMR (500 MHz, CDCl3): d¼6.77 (s, 4H), 3.93 (t,
J¼6.0 Hz, 4H), 2.59–2.54 (m, 8H), 1.70–1.65 (m, 4H),
1.51–1.38 (m, 12H), 1.35–1.30 (m, 4H), 1.27–1.23 (m,
4H), 1.19 (s, 2H). 13C NMR (125 MHz, CDCl3): d¼202.80,
154.41, 134.13, 129.23, 129.00, 127.72, 125.99, 125.41,
123.40, 120.68, 115.81, 69.51, 43.47, 29.01, 28.33, 25.20,
11. (a) Cuny, G. D.; Buchwald, S. L. J. Am. Chem. Soc. 1993, 115,
2066–2068. (b) Moasser, B.; Gladfelter, W. L. Organo-
metallics 1995, 14, 3832–3838.
21.64. IR (film, NaCl), n [cm21]¼2929, 1506, 1286. HRMS
~
12. (a) van der Veen, L. A.; Keeven, P. H.; Schoemaker, G. C.;
Reek, J. N. H.; Kamer, P. C. J.; van Leeuwen, P. W. N. M.;
Lutz, M.; Spek, A. L. Organometallics 2000, 19, 872–883.
(b) Kranenburg, M.; van der Burgt, Y. E. M.; Kamer, P. C. J.;
van Leeuwen, P. W. N. M.; Goubitz, K.; Fraanje, J.
Organometallics 1995, 14, 3081–3089.
(FAB): for C24H42N2O2 calcd: 391.3325 [MþH]þ; found:
391.3319.
Acknowledgements
13. Kranemann, C. L.; Eilbracht, P. Synthesis 1998, 71–77.
´ ´
14. (a) Joseph, B.; Chapellier, V.; Merour, J.-Y.; Leonce, S.
We are grateful to Deutscher Akademischer Austausch-
dienst (DAAD) for financinal support. We also thank
Degussa-Hu¨ls AG Frankfurt for donations of chemicals.
Heterocycles 1998, 48, 1423–1430. (b) Mouadibb, A.; Joseph,
´
´
B.; Hasnaoui, A.; Merour, J.-Y.; Leonce, S. Heterocycles
1999, 51, 2127–2137. (c) Dinsmore, C. J.; Bergman, J. M.
J. Org. Chem. 1998, 63, 4131–4134. (d) Rocaboy, C.; Bauer,
W.; Gladysz, J. A. Eur. J. Org. Chem. 2000, 2621–2628.
15. (a) Roffia, P.; Conti, F.; Gregorio, G.; Pregaglia, G. F.
J. Organomet. Chem. 1973, 54, 357–360. (b) Wang, Z.-M.;
Shen, M. J. Org. Chem. 1998, 63, 1414–1418.
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