First stereoselective pinacol coupling in the [2.2]paracyclophane series

Article abstract of DOI:10.1016/S0957-4166(02)00315-4

The planar chiral N-arylimines of [2.2]paracyclophane undergo stereoselective pinacol coupling under the action of the Zn/Cu couple in the presence of p-TosOH, thus forming N-aryl substituted 1,2-diamines. The stereoselective formation of the asymmetric c

Full text of DOI:10.1016/S0957-4166(02)00315-4

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 13 (2002) 1121–1123
First stereoselective pinacol coupling in the
[2.2]paracyclophane series
Elena V. Sergeeva,a Valeria I. Rozenberg,a,* Dmitrii Yu. Antonov,a Evgenii V. Vorontsov,a
Zoya A. Starikovaa and Henning Hopfb,*
aA. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Science, Vavilova 28, 119991 Moscow, Russia
bInstitute of Organic Chemistry, Technical University of Braunschweig, Hagenring 30, D-38106 Braunschweig, Germany
Received 14 May 2002; accepted 10 June 2002
Abstract—The planar chiral N-arylimines of [2.2]paracyclophane undergo stereoselective pinacol coupling under the action of the
Zn/Cu couple in the presence of p-TosOH, thus forming N-aryl substituted 1,2-diamines. The stereoselective formation of the
asymmetric centers is governed by the planar chiral [2.2]paracyclophanyl moiety. © 2002 Elsevier Science Ltd. All rights reserved.
In the course of our continuing studies directed at the
synthesis of planar chiral [2.2]paracyclophanes as lig-
ands for asymmetric synthesis we have already reported
a number of efficient methods allowing, inter alia, the
preparation of optically pure ortho-formyl- and ortho-
acylhydroxy[2.2]paracyclophanes and their imines, b-
diketones, etc.1 Herein we describe the first synthesis of
[2.2]paracyclophane based chiral N-aryl substituted 1,2-
diamines by stereoselective pinacol coupling of the cor-
responding N-arylimines.
For this purpose we have synthesized a number of
novel racemic and enantiomerically pure Schiff bases
4–8 by heating aldehydes 1–3 with the corresponding
arylamines in refluxing toluene in the presence of an
Et2SnCl2 catalyst (Scheme 1). Aldehydes ( )- and (Rp)-
Scheme 1.
* Corresponding authors. Tel.: 007-095-135-9268, fax: 007-095-135-5085 (V.I.R.); Tel.: +49(0)531-391-5255, fax: +49(0)531-391-5388 (H.H.);
e-mail: lera@ineos.ac.ru; h.hopf@tu-bs.de
0957-4166/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(02)00315-4

1122
E. V. Sergee6a et al. / Tetrahedron: Asymmetry 13 (2002) 1121–1123
1, ( )- and (Rp)-3 were synthesized by the previously
described procedures.1–3 For the synthesis of ( )- and
(Rp)-2 an efficient para-regioselective formylation of
4-methoxy[2.2]paracyclophane (similar to regioselective
acylation1) has been carried out.
imine could give two chiral C2-symmetrical diamines,
differing in the configuration of the benzylic centers,
and one unsymmetrical diastereomer.
1
According to the H NMR data, the coupling of the
racemic imines 4–8 occurs with formation of mixtures
of two diastereomers either in a 1:1 ratio (Table 1,
entries 1, 3, and 5) or with a noticeable excess of one
diastereomer (Table 1, entries 4 and 7). No traces of the
reduction product (the corresponding amine) were
detected. The presence of only one half set of signals in
the 1H NMR spectra of diamines 9–13 indicate the
formation of symmetrical compounds. Crystallization
of 10 and 11 allowed the isolation of individual crys-
talline diastereomers, and their structures were deter-
mined by X-ray analysis5 as meso-10 and meso-11
(major) of (Rp,S,R,Sp) relative configurations (Fig. 1).
Next we carried out the coupling of imines (Rp)-4,
(Rp)-7 and (Rp)-8 (Table 1, entries 2, 6 and 8) and
observed in each case the stereoselective formation of
the single chiral products 9, 12 and 13.6 By comparison
The coupling reactions of the imines were performed
under conditions similar to those described for different
aldehyde derivatives in the arene series.4 DMF solu-
tions of 4–8 were mixed with excess Zn/Cu couple and
p-TosOH at 0°C and then stirred at room temperature
for 24 h (Scheme 1). After workup the crude products
1
were analyzed by H NMR spectroscopy to determine
the diastereomeric ratio of the product (Table 1). The
diamines 9–13 were purified by chromatography on
silica gel and characterized as diastereomeric mixtures
or individual compounds by spectroscopic and chemical
analyses.
The pinacol coupling of the [2.2]paracyclophane-
derived imines produces diamines, bearing two planar
chiral moieties and two asymmetric centers. Starting
from racemic imines a mixture of six diastereomers
could in principle be obtained, from which two dl-pairs
and two meso-compounds have symmetry (C2 and C1,
respectively). The coupling of the enantiomerically pure
1
of the H NMR spectra the alternate products formed
in the coupling of racemic 4, 7 and 8 could be assigned
as meso-diastereomers. The relative configuration of the
diastereomerically pure 13 was determined as
1
(Rp,S,S,Rp) by 2D H NMR experiments.
Table 1. Pinacol coupling of the imines 4–8 with Zn/Cu couple and p-TosOH
Entry
R
R1
Imine
Diamine
Isolated yield (%)
dl:mesoa or [h]2D2
1
2
3
4
5
6
7
8
H
H
H
H
Ph
Ph
4
9
60
64
40
67
64
46
35
35
50:50
(Rp)-4
5
6
7
(Rp,S,S,Rp)-97
−15.7 (c 0.36, C6H6)
51:49
15:85
50:50
+49.4 (c 0.23, C6H6)
25:75
+28.7 (c 0.27, C6H6)
2-BrC6H4
2,6-Me2-C6H3
Ph
Ph
Ph
Ph
105
115
p-OCH3
p-OCH3
o-OCH3
o-OCH3
12
(Rp)-7
(Rp,S,S,Rp)-128
13
85
(Rp)-8
(Rp,S,S,Rp)-139
a Determined by 1H NMR analysis of the reaction mixtures.
Figure 1.

E. V. Sergee6a et al. / Tetrahedron: Asymmetry 13 (2002) 1121–1123
1123
Relying on the established relative configurations for
References
meso-10 and 11 and chiral 13 we assume that the planar
chiral [2.2]paracyclophane moiety plays a key role in
the stereochemical outcome of the reaction. Thus, if the
activated imine fragment of compounds 4–7 react in
anti conformation to the nearest ethylene bridge, the
Si-site (for the (Rp)-enantiomer) or Re-site (for the
(Sp)-enantiomer) should not be shielded by the protons
of the unsubstituted [2.2]paracyclophane ring. Coupling
between paracyclophanyl fragments with opposite
configurations, i.e. (Rp)- and (Sp), should lead to the
meso-diastereomer with (Rp,S,R,Sp)-configuration,
which was unequivocally established for 10 and 11,
whereas the coupling of two paracyclophanyl fragments
with the same absolute configuration should give rise to
the (Rp,S,S,Rp)- or (Sp,R,R,Sp)-diamines. At the
same time the X-ray structure of the imine 85 bearing
an ortho-substituent reveals that now the more prefer-
able conformation of the imine fragment is the one with
the N-Ph substituent in syn-orientation to the ethylene
bridge, due to the repulsive interaction with the OCH3
group. Thus, the stereochemical outcome of the cou-
pling reaction should be opposite to that observed for
the reaction of the imines 4–7. However, for the imine
8 (and hence for the diamine 13) the configuration of
the planar chiral [2.2]paracyclophane fragment changes
because of the nomenclature priority of the OCH3
group over the imino group. Hence the coupling of
paracyclophanyl fragments having opposite configura-
tions should give (Rp,S,R,Sp)-13, whereas the coupling
of two paracyclophanes with the same configurations
should afford (Rp,S,S,Rp)-/(Sp,R,R,Sp)-13.
1. (a) Rozenberg, V.; Danilova, T.; Sergeeva, E.; Vorontsov,
E.; Starikova, Z.; Lysenko, K.; Belokon’, Yu. Eur. J.
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(b) Hopf, H.; Barrett, D. G. Liebigs Ann. 1995, 449–451.
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S. J. Mol. Catal. A: Chem. 1996, 113, 77–86.
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E.; Starikova, Z.; Korlyukov, A.; Hopf, H. Eur. J. Org.
Chem. 2002, 468–477.
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609–610.
5. Crystallographic data for the diamines 8, 10 and 11 are
available from the Cambridge Crystallographic Data
Center, 12 Union Road, Cambridge CB2 1EZ, UK,
e-mail: deposit@ccdc.cam.ac.uk; the CCDC numbers are
185284, 185285 and 185286, respectively.
6. For similar regularities in the pinacol coupling of racemic
and enantiomerically pure planar chiral (benz-
aldimine)Cr(CO)3, see: Taniguchi, N.; Uemura, M. Tet-
rahedron 1998, 54, 12775–12788.
7. (Rp,S,S,Rp)-9: Mp 125–126.5°C.—C46H44N2 (624.87)
calcd: C, 88.42; H, 7.10; N, 4.48; found: C, 88.49; H,
7.39; N, 4.04%.—1H NMR (C6D6): l=2.30–2.40 (m,
2H), 2.60–2.90 (m, 12H), 3.35–3.44 (m, 2H), 4.13 (d,
3
3J=9.35 Hz, 2H, 2CH), 5.20 (d, J=9.35 Hz, 2H, 2NH),
5.53 (s, 2H), 6.10 (d, 3J=7.8 Hz, 2H), 6.24–6.53 (m,
10H), 6.88 (m, 2H), 6.98 (m, 4H), 7.30 (m, 4H).—13C
NMR (CDCl3): l=34.19, 34.96, 35.21 (2C), 56.62, 113.12
(2C), 117.60, 129.80 (2C), 131.05, 131.84, 132.09, 132.16,
132.23, 132.65, 134.41, 135.47, 137.28, 138.75, 139.01,
139.11, 147.74.—MS (70 eV); m/z (%): 312 (49) [M+/2].
8. (Rp,S,S,Rp)-12: Mp 109.5–112°C.—C48H48N2O2 (684.92)
calcd: C, 84.17; H, 7.06; N, 4.09; found: C, 83.97; H,
7.39; N, 3.84%.—1H NMR (CDCl3): l=2.15–2.27 (m,
2H), 2.56–2.67 (m, 2H), 2.72–2.82 (m, 2H), 2.84–2.98 (m,
6H), 3.04–3.25 (m, 4H), 3.74 (s, 6H, 2OCH3), 3.84 (br.s,
2H, 2CH), 4.94 (br.s, 2H, 2NH), 5.32 (s, 2H), 5.60 (s,
2H), 5.99 (d, 2H), 6.25 (d, 2H), 6.36 (d, 2H), 6.65 (d, 2H),
6.78–6.87 (m, 6H), 7.28–7.36 (m, 4H).—13C NMR
(CDCl3): 31.61, 33.35, 33.76, 34.75, 54.10, 55.85, 113.24
(2C), 117.34, 117.48, 126.08, 128.00, 128.06, 129.75 (3C),
130.58, 132.35, 132.72, 133.35, 138.07, 139.27, 139.71,
147.85, 156.41.—MS (70 eV); m/z (%): 342 (16) [M+/2].
9. (Rp,S,S,Rp)-13: Mp 227.5–229°C.—C48H48N2O2 (684.92)
calcd: C, 84.17; H, 7.06; N, 4.09; found: C, 84.27; H,
7.20; N, 4.13%.—1H NMR (CDCl3): l=2.45–2.58 (m,
2H), 2.65–2.79 (m, 4H), 2.83–2.96 (m, 4H), 2.98–3.06 (m,
2H), 3.07–3.16 (m, 4H), 3.43 (s, 6H, 2OCH3), 4.75 (br.d,
2H, 2CH), 6.08 (d, 2H, 2NH), 6.12–6.20 (m, 4H), 6.29 (d,
2H), 6.42 (d, 2H), 6.47 (d, 2H), 6.53 (d, 2H), 6.60–6.70
(m, 6H), 7.15–7.25 (m, 4H).—13C NMR (CDCl3): 32.49,
34.66, 34.88, 34.96, 61.16, 61.87, 112.30 (2C), 116.01,
129.17, 129.35, 129.75 (2C), 130.70, 131.10, 131.87,
132.61, 132.83, 135.63, 138.98, 139.31, 140.76, 149.35,
159.56.—MS (70 eV); m/z (%): 342 (20) [M+/2].
In conclusion, the pinacol coupling of the enantiomeri-
cally pure planar chiral N-aryl substituted imines of
[2.2]paracyclophane occurs stereoselectively giving rise
to diastereomerically pure diamines. Coupling of the
racemic imines produces a mixture of the single racemic
dl- and single meso-diamines. The newly synthesized
chiral compounds can be regarded as potential chiral
ligands in a wide range of stereoselective reactions
proceeding with participation of chiral diamines.10 The
scope of the application of the pinacol coupling to the
synthesis of other [2.2]paracyclophane based diamines
(N-unsubstituted or N-alkyl substituted), diols and
amino alcohols possessing planar and central chirality
applying either the Zn–sulfonic acid system or other
classical reagents (such as Sm and low valent Ti deriva-
tives, etc.) is now in progress.
Acknowledgements
Financial support of this work by Russian Science
Foundation (00-03-32683a and 00-03-32807a) is grate-
fully acknowledged.
10. Bennani, Y. L.; Hanessian, S. Chem. Rev. 1997, 97,
3161–3195.