Palladium-catalyzed amination in the synthesis of macrocycles comprising cholane, polyamine and pyridine units

Article abstract of DOI:10.1016/j.tetlet.2007.12.049

3,24-Bis(6-chloropyridin-2-yloxy)cholane, obtained from 3,24-cholandiol via a Mitsunobu reaction, was successfully used for the synthesis of a variety of polyazamacrocycles using Pd-catalyzed amination reaction with linear polyamines. The competing formation of cyclodimers and other cyclic oligomers was found to be strongly dependent on the nature of the polyamines employed.

Full text of DOI:10.1016/j.tetlet.2007.12.049

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 1188–1191
Palladium-catalyzed amination in the synthesis of macrocycles
comprising cholane, polyamine and pyridine units
a,
a
a
b
*
Alexei D. Averin , Elena R. Ranyuk , Nikolai V. Lukashev , Svetlana L. Golub ,
Alexei K. Buryak b, Irina P. Beletskaya a,b,
*
a Lomonosov Moscow State University, Department of Chemistry, Leninskie Gory, Moscow 119992, Russia
b A. N. Frumkin Institute of Physical and Electrochemistry, 31 Leninskii Prosp., Moscow 119991, Russia
Received 12 October 2007; revised 30 November 2007; accepted 10 December 2007
Available online 15 December 2007
Abstract
3,24-Bis(6-chloropyridin-2-yloxy)cholane, obtained from 3,24-cholandiol via a Mitsunobu reaction, was successfully used for the syn-
thesis of a variety of polyazamacrocycles using Pd-catalyzed amination reaction with linear polyamines. The competing formation of
cyclodimers and other cyclic oligomers was found to be strongly dependent on the nature of the polyamines employed.
Ó 2007 Elsevier Ltd. All rights reserved.
Macrocycles which contain 2–4 cholic acid fragments
linked with various spacers are known as cholaphanes
and are of great interest as molecular sensors. Steroidal
fragments can be bridged with amide,1–3 ester4–8 groups,
or with ethyleneglycol fragments.9 Another type of
steroid-based macrocycles resembles crown ethers and are
formed from compounds with one steroid unit and one
polyoxyalkyl chain attached.10–13 Recently, we have elabo-
rated another approach to steroid-based macrocycles
which is based on the palladium-catalyzed amination of
haloaryl derivatives of cholanediol with linear poly-
amines.14,15 Now we have attempted the catalytic synthesis
of steroid-based polyazamacrocycles using pyridine moie-
ties as aromatic linkers. This choice is explained by the
presence of an additional nitrogen atom in pyridine which
can facilitate complexation towards cations and polar mol-
ecules and also by a possible increase in biological activity
of the resulting compounds.
ane in absolute THF. The Mitsunobu reaction16 with
1 equiv of 6-chloropyridin-2-ol 3 provided monopyridin-
oxy derivative 4 in 84% yield (Scheme 1), in this case selec-
tive and complete substitution at C(24) occurred, which
was not the case when using 3-bromophenol.14 Treatment
O
OH
OH
H
NaBH4/BF3
THF, r.t.
H
H
H
H
H
HO
HO
H
H
2, 90%
1
1 equiv.
2.5 equiv.
HO
N
Cl
3
Ph3P, (EtO2CN=)2
THF, r.t.
O
N
O
N
H
The synthesis of 3,24-cholanediol 2 in 90% yield was
achieved by the reduction of the lithocholic acid 1 with bor-
Cl
H
H
H
O
Cl
H
H
H
N
HO
5, 85%
H
Cl
4, 84%
*
Corresponding authors. Tel.: +7 495 939 11 39; fax: +7 495 939 36 18
Scheme 1. Synthesis of mono- and di(6-chloropyridin-2-yloxy)cholanes
(A.D.A.).
4 and 5.
E-mail address: averin@org.chem.msu.ru (A. D. Averin).
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.12.049

A. D. Averin et al. / Tetrahedron Letters 49 (2008) 1188–1191
1189
same reaction with triamine 6b gave 25% of cyclodimer
8b and 46% of a mixture of cyclodimer 8b, cyclotrimer 9b
and cyclotetramer 10b (entry 2). The desired macrocycle
7b was registered only as a tiny component of a mixture
with cyclodimer 8b, in a MALDI mass spectrum (m/z
615.7 [M+]). The longer chain triamine 6c provided the tar-
get macrocycle 7c (10%) as a mixture with cyclodimer 8c in
ca. equimolar ratio, and a mixture of cyclodimer 8c, cyclo-
trimer 9c and cyclotetramer 10c was obtained separately in
33% yield (entry 3). A better result was observed in the case
of tetraamine 6d, macrocycle 7d was obtained in 26% yield
though it contained cyclodimer 8d as an admixture (entry
4). A slightly longer tetraamine 6e provided the best yield
of monomeric macrocycle 7e with its cyclodimer 8e, their
yields being 29% and 66%, respectively (entry 5). 1,3-
Bis(2-aminoethyl)adamantane 6f reacted with di(chloropy-
ridinyloxy)cholane 5 to afford macrocycle 7f with a valu-
able adamantyl spacer in 15% yield, and cyclic oligomers
were obtained as mixtures (22%, entry 6). Similar results
were obtained with oxadiamines 6g–i. While the shortest
dioxadiamine 6g afforded macrocycle 7g in a low 6% yield
(entry 7), the longer dioxadiamine 6h gave 7h in 22% yield
(entry 8) and the reaction with trioxadiamine 6i resulted in
a 21% yield of macrocycle 7i (entry 9). In these reactions
cyclooligomers were isolated in 35–75% yields.
O
O
N
N
H
H
HN
Cl
H
H
H
H
H2N
X
6a-i
NH2
O
O
H
H
N
N
X
Pd(dba)2/BINAP
8/9 mol%
tBuONa, dioxane
reflux, 15 h
5
N
Cl
H
7b-i
+
Cyclic oligomers:
H2N
NH2
6a:
6b:
6c:
6d:
6e:
H
N
O
H
N
H2N
H2N
H2N
H2N
NH2
N
N
H
NH2
H
N
NH2
H
N
H
H
H
N
H
N
NH2
H
H
X
O
H2N
N
6f:
NH
NH2
NH2
n
O
6g:
H2N
O
8: n = 2
9: n = 3
10: n = 4
O
NH2
NH2
6h:
6i:
H2N
H2N
O
O
O
O
Scheme 2. Synthesis of macrocycles 7.
of cholanediol 2 with 2.5 equiv of chloropyridinol under
Mitsunobu conditions gave an 85% yield of 3,24-di(6-chloro-
pyridin-2-yloxy)cholane 5 (Scheme 1).
The results of the catalytic amination with 3,24-di(6-
chloropyridin-2-yloxy)cholane 5 were found to be different
from those described earlier for 3,24-di(3-bromophen-
oxy)cholane.14 Yields of the target macrocycles 7 proved
to be in general lower and also the formation of large
amounts of cyclodimers and cyclic oligomers was observed.
This could be due to the lower reactivity of the chlorine
in the amination reaction compared to bromine, which
could lead to a lower rate of intramolecular amination after
the first chlorine substitution with the nitrogen of the poly-
amine. This intermediate could react with a second mole-
cule of compound 5 giving rise to oligomeric products
though sufficiently dilute solutions (c = 0.02 M) were
employed to suppress this undesirable effect. It should be
noted that cyclodimers 8 can exist as two regioisomers
(head-to-head and head-to-tail) which could not be
distinguished using NMR spectra. For cyclic oligomers 9
and 10 of higher mass a greater number of possible regioi-
somers can be proposed. However, cyclic monomers 7 and
Compound 5 was reacted in the palladium-catalyzed
amination reactions17,18 with various polyamines 6a–i
using 8 mol % Pd(dba)2 and 9 mol % BINAP in boiling
dioxane (c = 0.02 M), sodium tert-butoxide was employed
as a base (Scheme 2). The reactions were complete in
15 h, and the composition of the reaction mixtures was
1
identified by H and 13C NMR spectra prior to isolation
of the products by column chromatography on silica gel.
The yields of the target macrocycles 7 were found to be
strongly dependent on the nature of the starting poly-
amines 6, especially on the length of the aminoalkyl chains.
Application of the shortest 1,3-diaminopropane 6a
resulted in the formation of only cyclodimer 8a in 38%
yield (Table 1, entry 1). An additional amount (21%) of
cyclodimer 8a was obtained as a separate fraction in a
4:1:2 mole ratio with BINAP dioxide and dioxane. The
Table 1
Yields of macrocycles 7
Entry
Amine
Yield of 7
Yield of cyclic oligomers
1
2
3
4
5
6
7
8
9
6a
6b
6c
6d
6e
6f
0
8a, 38%; in a 4:1:2 mole ratio with BINAP dioxide and dioxane, 21%
8b, 25%; 8b+9b+10b, 46%
8c, 11%; 8c+9c+10c, 33%
Traces
7c, 10%
7d, 26%
7e, 29%
7f, 15%
7g, 6%
7h, 22%
7i, 21%
8e, 66%
Higher oligomers, 22%
8g, 7%; 9g, 7%; higher oligomers, 61%
8h, 12%; higher oligomers, 23%
8i, 10%; higher oligomers, 33%
6g
6h
6i

1190
A. D. Averin et al. / Tetrahedron Letters 49 (2008) 1188–1191
3,24-Di(6-chloropyridin-2-yloxy)cholane 5: 1H NMR (400 MHz,
CDCl3): d = 0.65 (s, 3H), 0.94 (d, J = 6.4 Hz, 3H), 0.97 (s, 3H),
1.02–2.03 (m, 28H), 4.20–4.28 (m, 2H), 5.31 (br s, 1H), 6.60 (dd,
J = 8.2, 0.6 Hz, 1H), 6.62 (dd, J = 8.2, 0.6, 1H), 6.82 (dd, J = 7.4,
0.6 Hz, 1H), 6.86 (dd, J = 7.4, 0.6 Hz, 1H), 7.46 (t, J = 7.8 Hz, 1H),
7.49 (t, J = 7.8 Hz, 1H); 13C NMR (100.6 MHz, CDCl3): d = 12.1,
18.6, 21.1, 23.8, 24.2, 24.8, 25.4, 26.2, 26.6, 28.2, 30.4, 30.6, 32.0, 34.9,
35.4, 35.7, 37.2, 39.9, 40.2, 42.7, 56.1, 56.6, 67.2, 71.9, 109.1, 109.7,
115.6, 115.9, 140.4 (2C), 148.3 (2C), 163.2, 163.7; MALDI-TOF m/z
584.48 M+.
Typical procedure for the amination of steroid compounds 4 and 5: A
two-neck flask equipped with a magnetic stirrer and a condenser was
charged with steroid compound 4 or 5 (0.5 mmol), absolute dioxane
(25 ml), Pd(dba)2 (24 mg, 8 mol %) and BINAP(28 mg, 9 mol %). The
mixture was stirred for 2 min, and then appropriate polyamine 6 was
added (0.5 mmol), and the reaction mixture was refluxed for 15 h.
After cooling to ambient temperature and filtration dioxane was
evaporated in vacuo and the residue was chromatographed on silica
gel using a sequence of eluents: CH2Cl2, CH2Cl2–MeOH 500:1–3:1,
CH2Cl2–MeOH–aqNH3 100:20:1–10:4:1.
Selected spectroscopic data: Cyclodimer 8a: 0.65 (s, 6H), 0.94 (d,
J = 6.4 Hz, 6H), 0.96 (s, 6H), 0.99–2.03 (m, 60H), 3.35 (dt, J = 7.3,
6.1 Hz, 8H), 4.08–4.18 (m, 4H), 4.49 (br s, 4H), 5.15 (s, 2H), 5.88 (d,
J = 7.9 Hz, 2H), 5.91 (d, J = 8.1 Hz, 2H), 5.98 (d, J = 7.9 Hz, 4H),
7.29 (t, J = 7.6 Hz, 2H), 7.30 (t, J = 7.7 Hz, 2H); 12.1 (2C), 18.7 (2C),
21.1 (2C), 23.8 (2C), 24.2 (2C), 25.0 (2C), 25.8 (2C), 26.3 (2C), 26.7
(2C), 28.3 (2C), 29.8 (2C), 30.7 (4C), 32.2 (2C), 34.9 (2C), 35.6 (2C),
35.7 (2C), 37.2 (2C), 39.8 (4C), 40.0 (2C), 40.3 (2C), 42.8 (2C), 56.3
(2C), 56.7 (2C), 66.3 (2C), 70.5 (2C), 97.3 (4C), 97.7 (2C), 98.2 (2C),
139.8 (2C), 139.9 (2C), 157.8 (4C), 163.0 (2C), 163.5 (2C); MALDI-
TOF m/z 1173.23 M+.
Macrocycle 7d: 1H NMR (400 MHz, CDCl3): d = 0.62 (s, 3H), 0.92
(br s, 6H), 0.95–2.02 (m, 32H), 2.70–3.05 (m, 8H), 3.32 (br s, 4H), 4.06
(br s, 2H), 5.09 (br s, 1H), 5.30 (br s, 2H), 5.85–5.97 (m, 4H), 7.19–
7.26 (m, 2H) (two NH protons of dialkylamino groups were not
unambiguously assigned); 13C NMR (100.6 MHz, CDCl3): d = 12.0,
18.6, 21.0, 23.8, 24.1, 24.9, 25.6, 26.2, 26.6, 28.2, 30.2 (2C), 20.6 (2C),
32.1, 34.8, 35.6 (2C), 37.1, 39.9 (2C), 40.2, 40.3, 42.6, 46.6 (2C), 47.1,
47.6, 56.1, 56.5, 66.2, 70.4, 97.4, 97.6, 98.5, 98.6, 139.7, 139.9, 157.7,
157.8, 162.7, 163.3; MALDI-TOF m/z 686.63 M+.
Macrocycle 7e: 1H NMR (400 MHz, CDCl3): d = 0.63 (s, 3H), 0.92
(d, J = 6.8 Hz, 3H), 0.94 (s, 3H), 0.96–2.15 (m, 34H), 2.78–2.95 (m,
8H), 3.35–3.50 (m, 4H), 4.08 (br s, 2H), 4.14–4.28 (m, 2H), 5.30 (br s,
1H), 5.84 (d, J = 7.6 Hz, 1H), 5.93 (d, J = 7.8 Hz, 1H), 5.96 (d,
J = 7.6 Hz, 2H), 7.23 (t, J = 7.8 Hz, 1H), 7.25 (d, J = 7.6 Hz, 1H)
(two NH protons of dialkylamino groups were not unambiguously
assigned); 13C NMR (100.6 MHz, CDCl3): d = 12.0, 18.8, 21.1, 23.0,
23.6, 24.1, 25.5, 26.3, 26.4, 27.7, 27.9, 28.2, 30.5, 31.0 (2C), 32.1, 34.2,
34.6, 35.3, 37.1, 39.0, 39.5, 40.3 (2C), 42.5, 46.6, 46.8, 46.9, 47.0, 53.9,
57.2, 66.3, 69.7, 97.2, 98.2,98.6, 99.0, 139.5, 139.7, 157.5, 157.6, 162.8,
163.1; MALDI-TOF m/z 701.44 [M+H]+.
Cyclodimer 8e: 1H NMR (400 MHz, DMSO-d6): d = 0.58 (s, 6H), 0.87
(br s, 12H), 0.90–2.02 (m, 68H), 2.75–3.00 (m, 16H), 3.24 (br s, 8H),
4.07 (br s, 4H), 5.13 (br s, 2H), 5.76 (br s, 4H), 5.96 (br s, 4H), 6.59 (br
s, 4H), 7.19 (br s, 4H); (four NH protons of dialkylamino groups were
not unambiguously assigned); 13C NMR (100.6 MHz, DMSO-d6):
d = 11.9 (2C), 18.5 (2C), 23.0 (2C), 23.4 (2C), 23.7 (2C), 24.6 (2C),
25.3 (2C), 25.9 (2C), 26.1 (2C), 26.2 (2C), 27.8 (2C), 27.9 (2C), 28.6
(2C), 30.5 (2C), 30.6 (2C), 31.9 (2C), 34.5 (2C), 35.1 (2C), 35.2 (2C),
36.5 (2C), 38.0 (4C), 42.3 (2C), 44.5 (2C), 44.7 (2C), 44.8 (2C), 45.2
(2C), 55.7 (2C), 56.0 (2C), 65.2 (2C), 69.3 (2C), 95.4 (2C), 96.3 (2C),
99.0 (4C), 139.4 (4C), 157.7 (4C), 162.2 (2C), 162.8 (2C) (four carbon
atoms in 39–40 ppm were hidden by CD3 multiplet of the solvent);
MALDI-TOF m/z 1402.15 [M+H]+.
cyclodimers 8 can be distinguished from 1H and 13C NMR
spectra of their pyridine moieties.19
Acknowledgements
This work was supported by RFBR Grant 06-03-32376
and by the Russian Academy of Sciences program P-8
‘Development of the methods of organic synthesis and con-
struction of the compounds with valuable properties’.
References and notes
1. Bonar-Law, R. P.; Davis, A. P. J. Chem. Soc., Chem. Commun. 1989,
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2. Davis, A. Chem. Soc. Rev. 1993, 22, 243–253.
3. Bhattarai, K. M.; Davis, A. P.; Perry, J. J.; Walter, C. J. J. Org.
Chem. 1997, 62, 8463–8473.
4. Kolehmainen, E.; Tamminen, J.; Lappalainen, K.; Torkkel, T.;
Seppa¨la¨, R. Synthesis 1996, 1082–1084.
5. Tamminen, J.; Kolehmainen, E.; Haapala, M.; Linnanto, J. Synthesis
2000, 1464–1468.
6. Zhang, Y.; Williams, W.; Torrence-Campbell, C.; Bowen, W. D.;
Rice, K. C. J. Med. Chem. 1998, 41, 4950–4957.
7. Pandey, P. S.; Rai, R.; Singh, R. B. J. Chem. Soc., Perkin Trans. 1
2002, 918–923.
8. Pandey, P. S.; Singh, R. B. Tetrahedron Lett. 1997, 38, 5045–5046.
9. Ra, C.; Cho, S.; Choi, J. Bull. Korean Chem. Soc. 2000, 21, 342–
344.
10. Babu, P.; Maitra, U. Proc. Indian Acad., Chem. Sci. 2003, 115, 607–
612.
11. Maitra, U.; Bag, B. G. J. Org. Chem. 1994, 59, 6114–6115.
12. Nair, V.; Prabhakaran, J. Synth. Commun. 1996, 26, 697–702.
13. Nair, V.; Prabhakaran, J.; Eigendorf, G. K. Synth. Commun. 1997, 27,
3095–3102.
14. Averin, A. D.; Ranyuk, E. R.; Lukashev, N. V.; Beletskaya, I. P.
Chem. Eur. J. 2005, 11, 1730–1739.
15. Lukashev, N. V.; Averin, A. D.; Latyshev, G. V.; Donez, P. A.;
Ranyuk, E. R.; Beletskaya, I. P. Polish J. Chem. 2006, 80, 559–572.
16. Mitsunobu, O. Synthesis 1981, 1.
17. Yang, B. H.; Buchwald, S. L. J. Organomet. Chem. 1999, 576, 125–
146.
18. Wolfe, J. P.; Buchwald, S. L. J. Org. Chem. 2000, 65, 1144–1157.
19. Synthesis of 24-(6-chloropyridin-2-yloxy)cholane 4: A two-neck flask
(250 ml) flushed with dry argon and equipped with a magnetic stirrer
was charged with 3,24-cholanediol (3 mmol, 1.086 g, obtained from
lithocholic acid14), absolute THF (75 ml), 2-chloro-6-hydroxypyridine
3 (3 mmol, 377 mg), triphenylphosphine (3 mmol, 786 mg) and diethyl
azodicarboxylate (DEAD) (3 mmol, 534 mg, 1.38 ml of a 40% soln in
toluene), and the reaction mixture was stirred at room temperature
overnight. THF was partially evaporated in vacuo, diethyl ether was
added to precipitate the majority of the triphenylphosphine oxide
which was filtered off. The resulting clear solution was evaporated and
chromatographed on silica gel using CH2Cl2 as eluent. Product 4 was
obtained as a colorless oil, yield 1.186 g (84%). For the synthesis of
3,24-di(6-chloropyridin-2-yloxy)cholane 5, 2.5 equiv of 2-chloro-6-
hydroxypyridine 3, triphenylphosphine and diethyl azodicarboxylate
were employed. Yield (from 3.7 mmol, 1.344 g of 3,24-cholanediol 2)
1.841 g (85%).
24-(6-Chloropyridin-2-yloxy)cholan-3-ol 4: 1H NMR (400 MHz,
CDCl3): d = 0.60 (s, 3H), 0.87 (s, 3H), 0.90 (d, J = 6.5 Hz, 3H),
0.95–1.96 (m, 28H), 2.14 (br s, 1H), 3.52–3.61 (m, 1H), 4.15–4.24 (m,
2H), 6.58 (d, J = 8.0 Hz, 1H), 6.82 (d, J = 7.6 Hz, 1H), 7.45 (t,
J = 7.8 Hz, 1H); 13C NMR (100.6 MHz, CDCl3): d = 12.1, 18.6, 20.8,
23.4, 24.2, 25.5, 26.4, 27.2, 28.2, 30.6, 32.0, 34.6, 35.3, 35.5, 35.8, 36.5,
40.2, 40.4, 42.1, 42.7, 56.2, 56.5, 67.2, 71.9, 109.1, 116.0, 140.4, 148.3,
163.8; MALDI-TOF m/z 473.44 M+.
Macrocycle 7f: 1H NMR (400 MHz, CDCl3): d = 0.64 (s, 3H), 0.92 (d,
J = 6.2 Hz, 3H), 0.96 (s, 3H), 1.00–2.03 (m, 44H), 2.04 (s, 2H), 3.19
(br s, 4H), 4.09–4.16 (m, 2H), 4.23 (br s, 2H), 5.15 (br s, 1H), 5.85 (d,
J = 8.0 Hz, 1H), 5.88 (d, J = 7.9 Hz, 1H), 5.97 (d, J = 7.8 Hz, 2H),

A. D. Averin et al. / Tetrahedron Letters 49 (2008) 1188–1191
1191
7.30 (t, J = 7.9 Hz, 1H), 7.31 (t, J = 7.8 Hz, 1H); 13C NMR
(100.6 MHz, CDCl3): d = 12.1, 18.7, 21.1, 23.9, 24.3, 25.0, 25.8,
26.3, 26.7, 28.3, 29.0 (2C), 30.8 (2C), 32.2, 32.7 (2C), 34.9, 35.6, 35.7,
36.5, 37.2 (3C), 40.0, 40.3, 42.0 (4C), 42.8, 43.7 (2C), 47.7, 56.3, 56.7,
66.2, 70.4, 96.7, 97.2, 97.3, 98.2, 139.9 (2C), 157.8, 157.9, 162.9, 163.5;
MALDI-TOF m/z 734.77 M+.
Macrocycle 7g: 1H NMR (400 MHz, CDCl3): d = 0.64 (s, 3H), 0.94
(d, J = 7.0 Hz, 3H), 0.95 (s, 3H), 0.99–2.05 (m, 28H), 3.40–3.48 (m,
2H), 3.58 (q, J = 4.9 Hz, 2H), 3.61–3.72 (m, 8H), 4.07–4.17 (m, 1H),
4.28–4.34 (m, 1H), 4.36 (br s, 1H), 4.67 (t, J = 4.8 Hz, 1H), 5.35 (br s,
1H), 5.87 (d, J = 7.5 Hz, 1H), 5.94 (J = 8.1 Hz, 1H), 5.96 (d,
J = 7.8 Hz, 1H), 5.98 (d, J = 7.9 Hz, 1H), 7.24 (t, J = 8.0 Hz, 1H),
7.28 (t, J = 7.9 Hz, 1H); 13C NMR (100.6 MHz, CDCl3): d = 12.1,
18.6, 21.2, 22.6, 23.5, 24.0, 25.3, 26.0, 26.2, 28.3, 30.0, 30.3, 31.3, 34.5
(2C), 35.2, 37.2, 40.6, 40.7, 41.2, 41.4, 42.5, 53.4, 58.0, 66.3, 70.1, 70.2,
70.3, 70.5, 70.7, 98.2, 98.3, 98.6, 98.7, 139.5, 139.7, 157.1, 157.4, 163.0,
163.1; MALDI-TOF m/z 660.65 M+.
Cyclodimer 8g: 1H NMR (400 MHz, CDCl3): d = 0.64 (s, 6H), 0.92 (d,
J = 6.0 Hz, 6H), 0.95 (s, 6H), 0.99–2.00 (m, 56H), 3.45 (br s, 8H), 3.64
(s, 8H), 3.67 (br s, 8H), 4.12 (br s, 4H), 4.79 (br s, 4H), 5.20 (br s, 2H),
5.86 (d, J = 7.7 Hz, 2H), 5.90 (d, J = 7.8 Hz, 2H), 5.98 (d, J = 7.7 Hz,
4H), 7.29 (t, J = 7.7 Hz, 4H); 13C NMR (100.6 MHz, CDCl3):
d = 12.0 (2C), 18.6 (2C), 21.1 (2C), 23.8 (2C), 24.2 (2C), 24.9 (2C),
25.7 (2C), 26.3 (2C), 26.6 (2C), 28.3 (2C), 30.6 (2C), 30.7 (2C), 21.1
(2C), 34.8 (2C), 35.5 (2C), 35.6 (2C), 37.1 (2C), 39.9 (2C), 40.3 (2C),
41.7 (4C), 42.7 (2C), 56.1 (2C), 56.6 (2C), 66.2 (2C), 69.9 (4C), 70.2
(6C), 97.3 (4C), 98.0 (2C), 98.5 (2C), 139.7 (2C), 139.8 (2C), 157.6
(4C), 162.8 (2C), 163.4 (2C); MALDI-TOF m/z 1321.15 M+.
Macrocycle 7h: 1H NMR (400 MHz, CDCl3): d = 0.64 (s, 3H), 0.92
(d, J = 6.8 Hz, 3H), 0.95 (s, 3H), 0.99–2.05 (m, 36H), 3.25–3.48 (m,
8H), 3.55 (t, J = 6.2 Hz, 4H), 4.12–4.20 (m, 1H), 4.25–4.33 (m, 1H),
4.43 (br s, 1H), 5.00 (br s, 1H), 5.30 (br s, 1H), 5.80 (d, J = 7.7 Hz,
1H), 5.91 (d, J = 7.8 Hz, 1H), 5.95 (d, J = 7.9 Hz, 1H), 5.96 (d, J =
7.7 Hz, 1H), 7.28 (t, J = 7.8 Hz, 2H); 13C NMR (100.6 MHz, CDCl3):
d = 12.0, 18.7, 21.1, 22.7, 23.8, 24.1, 25.2, 26.2, 26.4, 26.8, 26.9, 28.1,
29.3, 29.7, 30.3, 30.7, 30.9, 34.3, 34.7, 35.4, 37.2, 39.4, 40.3, 40.4, 41.6,
42.3, 53.8, 57.3, 66.4, 69.1, 69.6, 70.7, 71.0, 71.2, 96.4, 97.9, 98.2, 98.6,
139.6, 139.7, 157.6, 157.8, 162.8, 163.1; MALDI-TOF m/z 716.72 M+.
Cyclodimer 8h: 0.64 (s, 6H), 0.93 (d, J = 5.9 Hz, 6H), 0.96 (s, 6H),
1.00–2.02 (m, 72H), 3.32 (br s, 8H), 3.44 (br s, 8H), 3.52 (br s, 8H),
4.13 t, J = 6.4 Hz + 4.15–4.25 m (4H), 4.67 (br s, 4H), 5.16 br s + 5.21
br s (2H), 5.85 (d, J = 7.4 Hz, 2H), 5.89 (d, J = 8.4 Hz, 2H), 5.96 (d,
J = 7.8 Hz, 4H), 7.28 (t, J = 7.6 Hz, 2H), 7.30 (d, J = 7.7 Hz, 2H);
13C NMR (100.6 MHz, CDCl3): d = 12.0 (2C), 18.6 (2C), 21.1 (2C),
23.8 (2C), 24.2 (2C), 25.0 (2C), 25.7 (2C), 26.2 (2C), 26.5 (4C), 26.6
(2C), 28.3 (2C), 29.4 (4C), 30.7 (4C), 32.1 (2C), 34.9 (2C), 35.5 (2C),
35.6 (2C), 37.1 (2C), 40.0 (2C), 40.1 (2C), 40.2 (2C), 40.3 (2C), 42.7
(2C), 56.1 + 56.2 (2C), 56.7 (2C), 66.1 (2C), 69.1 (2C), 69.2 (2C),
70.1 + 70.3 (2C), 70.8 (4C), 96.8 + 96.9 (2C), 97.1 + 97.2 (4C),
98.0 + 98.3 (2C), 139.7 + 139.8 (4C), 157.9 (4C), 162.8 (2C), 163.4
(2C); MALDI-TOF m/z 1433.33 M+.
Macrocycle 7i: 1H NMR(400 MHz, CDCl3): d = 0.64 (s, 3H), 0.91 (d,
J = 6.7 Hz, 3H), 0.95 (s, 3H), 1.00–2.01 (m, 28H), 1.87 (quintet,
J = 6.1 Hz, 2H), 1.91 (quintet, J = 6.3 Hz, 2H), 3.33 (br s, 2H), 3.38
(q, J = 6.0 Hz, 2H), 3.56–3.65 (m, 12H), 4.17–4.23 (m, 1H), 4.24–4.31
(m, 1H), 4.47 (br s, 1H), 4.75 (br s, 1H), 5.31 (br s, 1H), 5.81 (d,
J = 7.9 Hz, 1H), 5.89 (d, J = 7.7 Hz, 1H), 5.94 (d, J = 7.7 Hz, 1H),
5.96 (d, J = 7.8 Hz, 1H), 7.26 (t, J = 7.9 Hz, 1H), 7.28 (t, J = 7.9 Hz,
1H); 13C NMR (100.6 MHz, CDCl3): d = 12.0, 18.7, 21.1, 23.0, 23.7,
24.1, 25.1, 26.1, 26.4, 28.0, 29.4, 29.5, 30.4, 30.9, 31.0, 34.4., 34.7, 35.4,
37.2, 39.3, 40.2, 40.3, 40.6, 42.5, 54.0, 57.2, 66.2, 69.4, 69.7, 70.1, 70.2,
70.5, 70.6, 70.7, 96.9, 97.8 (2C), 98.5, 139.6, 139.7, 157.5, 157.6, 162.8,
163.0; MALDI-TOF m/z 732.73 M+.
Cyclodimer 8i: 1H NMR (400 MHz, CDCl3): d = 0.64 (s, 6H), 0.92 (d,
J = 6.2 Hz, 6H), 0.95 (s, 6H), 0.99–2.00 (m, 64H), 3.32 (q, J = 6.9 Hz,
8H), 3.52–3.67 (m, 24H), 4.12 (t, 5.6 Hz, 4H), 4.71 (br s, 4H), 5.19 (br
s, 2H), 5.86 (d, J = 7.9 Hz, 2H), 5.89 (d, J = 8.0 Hz, 2H), 5.95 (d,
J = 7.8 Hz, 4H), 7.27 (t, J = 7.7 Hz, 2H), 7.28 (t, J = 8.0 Hz, 2H); 13
C
NMR (100.6 MHz, CDCl3): d = 12.1 (2C), 18.6 (2C), 21.1 (2C), 23.8
(2C), 24.2 (2C), 25.0 (2C), 25.7 (2C), 26.3 (2C), 26.6 (2C), 28.3 (2C),
29.3 (4C), 30.7 (4C), 32.1 (2C), 34.9 (2C), 35.6 (2C), 35.7 (2C), 37.1
(2C), 39.7 (2C), 39.8 (2C), 40.0 (2C), 40.3 (2C), 42.7 (2C), 56.2 (2C),
56.7 (2C), 66.2 (2C), 69.4 (6C), 70.2 (4C), 70.6 (4C), 97.0 (4C), 97.1
(2C), 97.5 (2C), 139.8 (4C), 157.9 (4C), 162.8 (2C), 163.4 (2C);
MALDI-TOF m/z 1465.33 M+.