Synthesis of novel N,O-planar chiral [2,2]paracyclophane ligands and their application as catalysts in the addition of diethylzinc to aldehydes

Article abstract of DOI:10.1016/S0957-4166(01)00102-1

A series of novel planar chiral N,O-[2,2]paracyclophane ligands were synthesised and applied as catalysts in the enantioselective addition of diethylzinc to aldehydes. The results indicate that the planar chirality of [2,2]paracyclophane, not the central chirality of the oxazoline, is the dominant stereocontrolling element.

Full text of DOI:10.1016/S0957-4166(01)00102-1

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 12 (2001) 529–532
Synthesis of novel N,O-planar chiral [2,2]paracyclophane ligands
and their application as catalysts in the addition of diethylzinc to
aldehydes
Xun-Wei Wu,a Xue-Long Hou,a,b,* Li-Xin Dai,a Ju Tao,a Bo-Xun Caoa and Jie Suna
aLaboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
354 Fenglin Lu, Shanghai 200032, China
bShanghai–Hong Kong Joint Laboratory in Chemical Synthesis, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, China
Received 29 January 2001; accepted 19 February 2001
Abstract—A series of novel planar chiral N,O-[2,2]paracyclophane ligands were synthesised and applied as catalysts in the
enantioselective addition of diethylzinc to aldehydes. The results indicate that the planar chirality of [2,2]paracyclophane, not the
central chirality of the oxazoline, is the dominant stereocontrolling element. © 2001 Elsevier Science Ltd. All rights reserved.
Planar chiral ligands play an important role in asym-
metric synthesis. In comparison with ferrocene
derivatives1 and arene transition metal complexes,2 little
attention has been paid to planar chiral ligands derived
from [2,2]paracyclophane and only a limited number of
reports have appeared on the study of planar chiral
[2,2]paracyclophane,3 and few of these works focus on
the applications of this class of compound as asymmet-
ric catalysts.3e–h,k,m,n,4 Recently, we reported the syn-
thesis of novel N,S- and N,Se-planar chiral
[2,2]paracyclophane ligands and their application in
palladium-catalysed allylic alkylation reactions.4 We
found that the planar chirality is the dominant factor in
controlling the stereoselectivity of the reaction. As part
of an ongoing study of chiral cyclophanes and part of a
program aimed at the applications of planar chirality in
asymmetric catalysis,5 we have synthesised a series of
novel disubstituted planar chiral N,O-ligands based on
the [2,2]paracyclophane backbone and found that they
efficiently catalyse the enantioselective addition of
diethylzinc to aldehydes. Herein, we communicate the
results of this study.
nucleus afforded the diastereoisomeric bromides 3 and
4,7 subsequent cyclisation of which8 provided the
diastereoisomeric pairs of oxazolinylcyclophanes 5 and
6, which were easily separable by column chromatogra-
phy to give workable yields of the pure compounds.
In separate reactions, bromo-lithium exchange of 5 and
6 at low temperature, followed by trapping of the anion
with benzophenone, gave the desired planar chiral N,O-
[2,2]paracyclophanes 7 and 8, respectively (Scheme 1).
The absolute configurations of planar chirality were
determined by X-ray diffraction of the precursors 5 and
6 and the X-ray crystal structures of 5d and 6c are
illustrated in Fig. 1. The configurations of 5d and 6c are
assigned as (19R,4Rp,13Sp) and (19S,4Sp,13Rp),
respectively.
With these ligands in hand, we turned our attention to
their application in catalytic asymmetric reactions. To
assess the paracyclophanes as catalytic ligands, their
effect on the enantioselective addition of diethylzinc to
aldehydes was examined. The results are shown in
Table 1.
Reaction of the racemic 4-carboxy [2,2]paracyclophane
16 with a number of enantiomerically pure aminoalco-
hols afforded the amide 2. Bromination at the aromatic
In the presence of a catalytic amount of ligand (5
mol%) the reaction proceeded smoothly to provide the
corresponding alcohol (Eq. (1)). Ligands 7a and 7c
afforded the best yields and enantioselectivities when
benzaldehyde was the substrate (Entries 1 and 5). Lig-
and 8d also showed good enantioselectivity, but lower
* Corresponding author. E-mail: xlhou@pub.sioc.ac.cn
0957-4166/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(01)00102-1

530
X.-W. Wu et al. / Tetrahedron: Asymmetry 12 (2001) 529–532
R1
O
COOH
R2
N
Br
O
+
N
R2
Br
6a-d
R1
5a-d
rac-1
a. (COCl)2
R1
PPh3/CCl4/Et3N/CH3CN
91-95%
96-97%
OH
R2
OH
b.
H2N
R1
R2
R1
O
O
R2
OH
N
H
N
H
H
N
Fe/Br2/CH2Cl2
Br
+
OH
R1
75-87%
R2
O
Br
2a-d
3a-d
4a-d
R1
R2
O
N
OH
Ph
BuLi/THF(-78oC)
5a-d
6a-d
O
+
Ph
N
7a-d, 75-88%;
8a-d, 62-72%
OH
Ph
R1
R2
Ph
7a-d
8a-d
Scheme 1. a: R1=H, R2=iPr; b: R1=H, R2=tBu; c: R1=H, R2=Bn; d: R1=Ph, R2=H.
Fig. 1. ORTEP illustrations of 5d and 6c with the atomic numbering.
ing group on the benzene ring as substrates but it is
lower than that from 1,2-disubstituted planar ferrocene
ligands when the substituent is electron-donating. The
difference of the configurations of planar and central
chiralities in these ligands markedly affects their reac-
tivity and their capacity for asymmetric induction.4,5,10
Ligands 7a, 7b, 7c and 8d showed higher reactivity and
reactivity than ligands 7a and 7c (Entry 8), while lig-
ands 7b, 7d, 8a, 8b and 8c showed both poor reactivity
and enantioselectivity.
When ligand 7c was used as catalyst, all aromatic
aldehydes reacted with diethylzinc to give the products
in high yield and e.e. It is interesting to compare the
results with those obtained when using ferrocene lig-
ands.9,10a The e.e. value obtained from 7c is higher than
that from both 1,2- and 1,1%-disubstituted ferrocene
ligands using benzaldehydes with an electron-withdraw-
OH
Ligand(5mol%)/Et2Zn(2.2eq.)
(1)
ArCHO
Ar
*
PhCH3

X.-W. Wu et al. / Tetrahedron: Asymmetry 12 (2001) 529–532
531
Table 1. Enantioselective addition of diethylzinc to aldehydes with planar chiral N,O-ligands 7 and 8
Entry
Ar
Ligand
Time (h)
Yield (%)a
E.e. (%)b
Config.c
1
2
3
4
5
6
7
8
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
7a
8a
7b
8b
7c
8c
7d
8d
7c
7c
7c
7c
7c
7c
9
24
24
24
7
24
24
18
8
9
24
4
20
9
96
35
37
13
93
12
12
85
96
95
86
94
87
95
93
5
32
7
93
7
5
87
94
93
82
81
86
95
R
S
R
S
R
S
S
S
9
p-ClC6H4
p-BrC6H4
p-MeOC6H4
o-MeOC6H4
a-Naphthyl
b-Naphthyl
R
R
R
R
R
R
10
11
12
13
14
a Isolated yield based on aldehyde.
b Determined by HPLC (Chiralcel OD column).
c Configurations were assigned by comparison with the sign of the specific rotation of known compounds.
induced higher enantioselectivity than the correspond-
ing diastereomeric ligands 8a, 8b, 8c and 7d. The
configuration of products from the reaction catalysed
by 7a–7c differs from that originated from 8a–8c. The
only exceptions were 7d and 8d, both of which gave the
(S)-configured product, despite the ligands having
opposing planar chirality. These results indicate that
the planar chirality and central chirality in 7a–7c and
8d are matched and act in a co-operative way in this
reaction; additionally this indicates that the planar chi-
rality of the [2,2]paracyclophane, not the central chiral-
ity of the oxazoline in 7 and 8, may be the dominant
stereocontrolling factor.
2. Bolm, C.; Muniz, K. Chem. Soc. Rev. 1999, 28, 51.
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T.; Yoneda, F. Tetrahedron: Asymmetry 1992, 3, 1387; (c)
Antonov, D. Y.; Belokon, Y. N.; Ikonnikov, N. S.;
Orlova, S. A.; Pisarevsky, A. P.; Raevski, N. I.; Rozen-
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Dubrovina, N. V.; Vorontsov, E. V.; Sergeeva, E. V.;
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lett 2000, 899.
In conclusion, we have successfully synthesised a series
of novel planar chiral N,O-ligands based on the
[2,2]paracyclophane backbone and demonstrated their
efficiency in asymmetric reactions.
The planar chirality of the [2,2]paracyclophane appears
to play a dominant role in the stereochemistry of the
reaction. The synthesis of similar ligands via introduc-
tion of other coordinating atoms and their applications
in asymmetric reactions is currently in progress.
Acknowledgements
Financial support from the Major Basic Research
Development Program (Grant No. G2000077506), the
National Natural Science Foundation of China,
National Outstanding Youth Fund, Chinese Academy
of Sciences, and Shanghai Committee of Science and
Technology is gratefully acknowledged.
4. Hou, X.-L.; Wu, X.-W.; Dai, L.-X.; Cao, B.-X.; Sun, J.
Chem. Commun. 2000, 1195.
5. (a) You, S.-L.; Zhou, Y.-G.; Hou, X.-L.; Dai, L.-X.
Chem. Commun. 1998, 2765; (b) Deng, W.-P.; Hou, X.-
L.; Dai, L.-X.; Yu, Y.-H.; Xia, W. Chem. Commun. 2000,
285; (c) Dai, L.-X.; Hou, X.-L.; Deng, W.-P.; You, S.-L.;
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S.-L.; Hou, X.-L.; Dai, L.-X. Tetrahedron: Asymmetry
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Dong, X.-W. Chem. Commun. 2000, 1483; (f) You, S.-L.;
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