Aryl[2.2]paracyclophane-based chiral regioisomeric analogs of salicyl aldehyde: Novel sources for construction of phenoxy-imine ligands

Article abstract of DOI:10.1002/ijch.201100096

The efficient, high-yield approaches to two novel regioisomeric salicyl aldehyde analogs, 4-formyl-13-(2-hydroxyphenyl)-[2.2]paracyclophane and 4-formyl-12-(2-hydroxyphenyl)-[2.2]paracyclophane (iso-FHPhPC and pseudo-FHPhPC, respectively), constructed on the basis of an aryl[2.2]paracyclophane backbone are described. The key stage of the backbone formation is the Suzuki cross-coupling of paracyclophanyl halides with arylboronic acids. Efficient procedures for the resolution of the racemic hydroxy aldehydes into enantiomers via Schiff bases with enantiomers of α-phenylethyl amine were elaborated, and the absolute configurations of enantiomers were established on the basis of X-ray analysis of diastereomeric imines. Starting from these chiral hydroxy aldehydes the first representatives of bi-, tri-, and tetradentate phenoxy-imine ligands belonging to an aryl[2.2]paracyclophane family were obtained. The induction power of the ligands was tested in the Et₂Zn asymmetric addition to aldehydes. Copyright

Full text of DOI:10.1002/ijch.201100096

Full Paper
R. P. Zhuravsky, V. I. Rozenberg et al.
DOI: 10.1002/ijch.201100096
Aryl[2.2]paracyclophane-Based Chiral Regioisomeric
Analogs of Salicyl Aldehyde: Novel Sources for
Construction of Phenoxy-Imine Ligands
Roman P. Zhuravsky,*[a] Tatiana I. Danilova,[a] Dmitrii Yu. Antonov,[a] Elena V. Sergeeva,[a]
Zoya A. Starikova,[a] Ivan A. Godovikov,[a] Michail M. Il’in,[a] and Valeria I. Rozenberg*[a]
Abstract: The efficient, high-yield approaches to two novel
regioisomeric salicyl aldehyde analogs, 4-formyl-13-(2-hy-
droxyphenyl)-[2.2]paracyclophane and 4-formyl-12-(2-hydrox-
yphenyl)-[2.2]paracyclophane (iso-FHPhPC and pseudo-
FHPhPC, respectively), constructed on the basis of an aryl-
[2.2]paracyclophane backbone are described. The key stage
of the backbone formation is the Suzuki cross-coupling of
paracyclophanyl halides with arylboronic acids. Efficient pro-
cedures for the resolution of the racemic hydroxy aldehydes
into enantiomers via Schiff bases with enantiomers of a-
phenylethyl amine were elaborated, and the absolute config-
urations of enantiomers were established on the basis of X-
ray analysis of diastereomeric imines. Starting from these
chiral hydroxy aldehydes the first representatives of bi-, tri-,
and tetradentate phenoxy-imine ligands belonging to an
aryl[2.2]paracyclophane family were obtained. The induction
power of the ligands was tested in the Et2Zn asymmetric ad-
dition to aldehydes.
Keywords: biaryls · cyclophanes · planar chirality · Schiff bases · Suzuki cross-coupling
1. Introduction
Salicyl aldehydes are bifunctional compounds the impor-
tance of which as building blocks in organic chemistry is
very well known.[1] They are used, for instance, for the
synthesis of coumarins possessing a wide spectrum of bio-
logical activity[2] or several natural products the prepara-
tion of which requires an o-quinone methide intermedi-
ate.[3] They are also actively employed in the synthesis of
various imines (Schiff bases in general, salenes in particu-
lar). These are most popular ligands since they are easily
obtainable from salicyl aldehydes by condensation with
amines, amino alcohols, and diamines while the imino-
products give rise to a rich coordination chemistry with a
wide range of metal ions.[4] The resulting complexes are
widely used in various areas, especially in supramolecular
chemistry (in modeling active sites of metalated en-
zymes[5] and for the construction of synthetic molecular
receptors[6] capable of selective recognition of enantio-
mers in various substrates), or as molecular loops and
squares,[7] as molecular building blocks for macromolecu-
lar matrices,[8] as olefin[9] oligo- and polymerisation cata-
lysts, and as asymmetric catalysis agents in various syn-
thetically important organic reactions.[10,11]
large substituents) into either the carbonyl or imino com-
ponent of the phenoxy-imine ligand. Chirality of the
Schiff base ligands can be created in various ways. The
achiral parent salicyl aldehyde would require chiral
amino derivative as the second component. With chiral
salicyl aldehydes, one may use either achiral or chiral
amino components[12,13] to get an imine that contains
either one or several stereogenic sites (the configurations
of which may be varied in order to establish an appropri-
ate chiral environment). Among some well-known chiral
hydroxy aldehydes there are salicyl aldehyde analogs
which bear elements of central (1),[14,15] axial (2),[15,16] or
planar
chirality
(3,
4-hydroxy-5-formyl-
[2.2]paracyclophane, FHPC)[17] (Figure 1), and the phen-
oxy-imine ligands based on them have been shown to be
good asymmetric inductors.[12,18]
[a] R. P. Zhuravsky, T. I. Danilova, D. Y. Antonov, E. V. Sergeeva,
Z. A. Starikova, I. A. Godovikov, M. M. Il’in, V. I. Rozenberg
A. N. Nesmeyanov Institute of Organoelement Compounds
Russian Academy of Science, Vavilova 28, 119911, Moscow,
Russia
The induction ability of the imine ligands used in asym-
metric catalysis certainly depends on the structure of the
parent salicyl aldehyde, and the ligand nature and archi-
tecture could further be optimized by introduction of var-
ious substituents (donor or acceptor groups, sterically
fax: +7 (499) 135-50-85
e-mail: zhuravsky.r@yandex.ru
vroz2003@yahoo.com
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/ijch.201100096.
156
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Aryl[2.2]paracyclophane-Based Chiral Regioisomeric Analogs of Salicyl Aldehyde
Figure 3. Salicyl aldehyde analogs of pseudo-biaryl type based on
an aryl[2.2]paracyclophane backbone.
Figure 1. Hydroxy aldehydes with various types of chirality.
As a part of our long-term project devoted to the regio-
selective synthesis of novel planar chiral [2.2]paracyclo-
phane derivatives and to their application as ligands in
stereoselective processes,[12,13,17,19–23] we have recently ob-
tained two novel FHPC analogs, namely 4-formyl-13-
groups in three aromatic rings, and we have introduced
their classification [biaryl, pseudo-biaryl (Figure 3), para-
cyclophanyl, and aryl types]. Key strategic approaches to
the synthesis of various ligands in enantiomerically pure
form were considered.[22]
In this paper we disclose the detailed synthesis of two
principally novel hydroxyaldehydes of the pseudo-biaryl
type constructed on the base of the aryl-
[2.2]paracyclophane backbone, namely iso-FHPhPC 6 (4-
Formyl-13-(2-HydroxyPhenyl)-[2.2]ParaCyclophane) and
hydroxy[2.2]paracyclophane
4[19]
and
4-formyl-12-
hydroxy[2.2]paracyclophane 5[20] (iso-FHPC and pseudo-
FHPC, Figure 2), the functional groups of which are situ-
ated in the different aromatic rings of the conformational-
pseudo-FHPhPC
7
(4-Formyl-12-(2-HydroxyPhenyl)-
[2.2]ParaCyclophane) (Figure 3), and their resolution into
enantiomers. In these compounds one functional group
(OH) belongs to the biaryl fragment while the other
group (CHO) is situated over this fragment in the second
paracyclophane aromatic ring in pseudo-gem (in 6) or
pseudo-ortho position (in 7) with respect to the aryl sub-
stituent. The spatial arrangement of these functional
groups could be varied due to free rotation around the
aryl[2.2]paracyclophane bond (in contrast to their rigid
fixation on the [2.2]paracyclophane backbone in iso-
FHPC and pseudo-FHPC), thus providing the possibility
of the additional fine tuning of the chiral environment.
Application of regioisomeric FHPhPC 6 and 7 for the
synthesis of the various phenoxy-imine ligands and dem-
onstration of their ability to act as chiral inductors in
Et2Zn addition to aldehydes are presented as well.
Figure 2. Planar chiral analogs of FHPC.
ly rigid [2.2]paracyclophane molecule (in pseudo-gem-po-
sition, one above the other; and in pseudo-ortho-position,
thus mimicking the classical salicylaldehyde itself). We
have also shown that bi- and tridentate Schiff bases de-
rived from 4 and 5 are highly enantioselective catalysts in
diethylzinc addition to aldehydes and display higher
chiral induction power in this reaction than do the Schiff
bases derived from 3 (up to 97% ee of the product).[20]
These results demonstrated that varying the mutual ar-
rangement of hydroxy and formyl functional groups in
the molecule of the chiral ligand (i.e., their deviation
from the position they occupy in salicyl aldehyde) is a
very promising project to be undertaken for the develop-
ment of various aspects of [2.2]paracyclophane stereo-
chemistry.[24]
Recently we proposed a new backbone for chiral li-
gands, viz. aryl[2.2]paracyclophane,[21,22] which unites a
conformationally flexible biphenyl fragment with the con-
figurationally rigid [2.2]paracyclophane moiety. We have
shown that the “hybrid” nature of the backbone allows
the construction of a wide range of chelating ligands
which may belong to essentially diverse types character-
ised by different mutual arrangement of their functional
2. Results and Discussion
2.1. Synthesis of iso-FHPhPC 6 and Its Resolution into
Enantiomers
The synthetic approach to racemic iso-FHPhPC 6 relies
on two general operations: 1) the generation of the
pseudo-gem substitution pattern by the regioselective bro-
mination of [2.2]paracyclophane carbonyl derivatives,[25]
and 2) the formation of the aryl[2.2]paracyclophane back-
bone by Suzuki cross-coupling reaction followed by fur-
ther transformations (Scheme 1).[21] 4-Methoxycarbonyl-
[2.2]paracyclophane 9 was obtained from parent [2.2]par-
acyclophane 8 by a multistep procedure described in the
literature.[26a] pseudo-gem-Regioselective bromination of
9[26]
produced
4-bromo-13-methoxycarbonyl-
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R. P. Zhuravsky, V. I. Rozenberg et al.
Scheme 1. Preparation of iso-FHPhPC 6 from [2.2]paracyclophane 8.
[2.2]paracyclophane 10, which then was introduced into
Suzuki cross-coupling with a double excess of anisylbor-
onic acid under non-aqueous conditions in the presence
of 1 to 2 mol% Pd(dppf)Cl2 catalyst. We have used two
solvent/base systems: THF/KF and toluene/K3PO4. The
first one produced the aryl[2.2]paracyclophane 11 in a
yield of 60% after refluxing the mixture for 55 h, while
some of the unreacted starting bromide 10 (25%) was re-
covered. The toluene/K3PO4 system was superior: the
yield of 11 was increased to 80% while refluxing for 30 h
only and the recovery rate of 10 was lower (15%).
To convert the key aryl[2.2]paracyclophane precursor
11 to the target iso-FHPhPC 6, we considered two routes,
A and B (Scheme 1). Route A comprises the reduction of
the methoxycarbonyl group in 11 by LiAlH4 in diethyl
ether leading to the methoxy carbinol 12 in quantitative
yield. The carbinol 12, oxidized under mild conditions
(DDQ, dioxane, RT), has produced the expected methoxy
aldehyde 13 in quantitative yield also. At the third stage
of Route A, however, after elimination of the methyl
group by refluxing 13 in an HBr/AcOH mixture, the de-
sired iso-FHPhPC 6 was obtained in a moderate yield
only (47%), while the reaction mixture did not contain
any other [2.2]paracyclophane derived compounds. Con-
sequently, the overall yield of 6 as obtained from 11 by
Route A was 45% only.
The same set of reagents and reaction conditions may
be applied in a different way, however. Thus we have
changed the sequence of converting the functional groups
of the precursor 11 (Scheme 1, Route B). Demethylation
of 11 was the first step in this case. The reaction was car-
ried out in a refluxing HBr/AcOH mixture and resulted
in the hydroxy carboxylic acid 14 in a yield of 98%. Re-
duction of 14 with LiAlH4 (Et2O, under reflux) produced
the respective carbinol 15 in quantitative yield. Oxidation
of this carbinol under conditions similar to those applied
in Route A produced the target iso-FHPhPC 6. The over-
all yield of 6 as obtained from 11 by Route B came up to
90%, thus making it more attractive for a preparative
synthesis of iso-FHPhPC. Note also that the procedure
for the synthesis of compound 6 may be simplified by
using the crude intermediates 14 and 15 (no purification
on silica gel or crystallisation is necessary). Nevertheless,
all novel [2.2]paracyclophane derivatives shown in
Scheme 1 were isolated as individual compounds and
1
characterised by H NMR spectra, mass spectra, and ele-
mental analyses. These compounds are attractive as po-
tential aryl[2.2]paracyclophane ligands of pseudo-biaryl
type or their precursors, and could be obtained in enan-
tiomerically pure form starting from enantiomers of
[2.2]paracyclophane-4-carboxylic acid.[27]
The resolution of iso-FHPhPC into enantiomers was
accomplished by a traditional approach repeatedly and
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Aryl[2.2]paracyclophane-Based Chiral Regioisomeric Analogs of Salicyl Aldehyde
Scheme 2. Resolution of iso-FHPhPC 6 into enantiomers.
successfully applied by us for the resolution of [2.2]para-
cyclophane based salicylaldehyde, its hydroxyaldehyde
analogs and hydroxyketones.[17a,b,19,20,22,23d,e] The elaborat-
ed procedure relies on the different solubility of the dia-
stereomeric Schiff bases formed from 6 with a-phenyle-
thylamine (a-PEAM) enantiomers. The diastereomeric
mixture of (Rp,Sc)- and (Sp,Sc)-16 was obtained in quanti-
tative yield by condensation of racemic 6 with (S)-a-
PEAM and it was crystallized from a toluene/hexane mix-
ture, then from ethanol, to produce (Sp,Sc)-16 in a yield of
58% (Scheme 2). The compound was diastereomerically
enantiomeric purity >99% as verified by HPLC analysis
on a Chiralpak AD-H column (retention times: (Sp)-6
tR =22.2 min; (Rp)-6 tR =26.4 min).
2.2. Synthesis of pseudo-FHPhPC 7 and Its Resolution into
Enantiomers
The synthetic approach to pseudo-FHPhPC 7 is based on
a stepwise selective exchange of the bromine substituents
in pseudo-ortho-dibromo[2.2]paracyclophane 18 that may
be accomplished in two ways: 1) bromine by phenyl via
Suzuki cross-coupling followed by the other bromine
moiety by formyl via monolithiation/formylation (Route
A), and 2) the reverse approach (Route B, Scheme 3) fol-
lowed by further transformations.
Dibromide 18 was obtained from paracyclophane 8 by
a two-step procedure worked out by us earlier.[28] It com-
prises a non-catalytic bromination of 8[29] followed by
thermal isomerisation of the intermediate pseudo-para-
dibromo[2.2]paracyclophane 17 into 18 in benzene in au-
toclave at 2008C with a high overall yield.
Along Route A the aryl[2.2]paracyclophane backbone
was built by Suzuki cross-coupling of 18 with anisylboron-
ic acid under non-aqueous conditions (2 mol% of Pd-
(dppf)Cl2/toluene/K3PO4).[21] The reaction was not chemo-
selective and it was accompanied by a side coupling at
both bromine atoms of 18 leading to a mixture of aryl-
[2.2]paracyclophane 19 and bis-aryl[2.2]paracyclophane
20 regardless of the starting dibromide/boronic acid ratio
used. The maximal yield of the desired 19 (51%) was
reached with three equivalents of the acid. The com-
pound 19 was easily separated from 20 (37%) by prepara-
tive chromatography on silica gel.
1
pure as confirmed by H NMR analysis. The partially re-
solved 6 was recovered by hydrolysis of the filtrate with
aqueous HCl in ethanol and introduced into the reaction
with (R)-a-PEAM. Crystallization of the mixture under
similar conditions produced diastereomerically pure
(Rp,Rc)-16 in 54% yield. The absolute configuration of
enantiomers 6 was determined by an X-ray structural
analysis of the single crystal of this diastereomer
(Figure 4). The individual enantiomers, (Rp)- and (Sp)-6,
were obtained by hydrolysis of (Rp,Rc)- and (Sp,Sc)-16
with 2 N HCl in ethanol in almost quantitative yields with
To introduce the formyl group, bromide 19 was lithiat-
ed (1.2 equiv of nBuLi in THF at À788C), then treated
with excess electrophile, DMF or N-formylpiperidine.
Figure 4. Molecular structure of (Rp,Rc)-16 in the solid state.
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Scheme 3. Preparation of pseudo-FHPhPC 7 from [2.2]paracyclophane 8.
With
DMF,
4-formyl-12-methoxyphenyl-
7 in a yield of 90%. Thus, Route B allowed us a fivefold
increase in the overall yield of 7 (from 18) and raised it
up to 50%. The other advantage of this approach is the
absence of the aryl[2.2]paracyclophane side products such
as 20 or 22. All this allows to use the Route B for a syn-
thesis of pseudo-FHPhPC in preparative satisfactory
amounts.
[2.2]paracyclophane 21 was obtained with a yield of 40%,
and 4-methoxyphenyl[2.2]paracyclophane 22 (30%) was
formed as a side product due to debromination of 19. N-
Formylpiperidine was more efficient, raising the yield of
21 up to 60% (together with 38% of 22 being formed).
The last stage of Route A, demethylation of 21, was car-
ried out as described above (HBr/AcOH, under reflux)
and produced the single paracyclophanyl product,
pseudo-FHPhPC 7, in a yield of 30% only. Consequently,
the overall yield of 7 as obtained from the dibromide 18
was very poor (no more than 9%).
This unsatisfactory result prompted us to elaborate an-
other, more efficient protocol to 7 which comprises 1) the
reversed order in the lithiation/formylation and cross-cou-
pling sequence, and 2) the use of a MOM-protecting
group instead of the Me group (Scheme 3, Route B). Ear-
lier[22] we had demonstrated that the formyl bromide 23
may be obtained in a yield of 40% by monolithiation[30]
of 18 followed by the treatment of the reaction mixture
with DMF. Replacement of DMF by N-formylpiperidine
(in analogy with the synthesis of 21) allowed us to raise
the yield of 23 up to 64%. Suzuki coupling of 23 with
ortho-MOMO-phenylboronic acid under standard condi-
tions (1 mol% of Pd(dppf)Cl2/toluene/K3PO4) produced
the MOM-protected aryl[2.2]paracyclophane 24 in a yield
of 87%. The MOM group was easily removed from 24 by
reflux in ethanol in the presence of a few drops of 36%
hydrochloric acid, leading to the target pseudo-FHPhPC
The hydroxyaldehyde 7 was resolved into its enantio-
mers in the same way as its regioisomer 6. Reaction of
the racemic 7 with (S)-a-PEAM produced a mixture of
diastereomeric Schiff bases, (Rp,Sc)- and (Sp,Sc)-25, in
quantitative yield (Scheme 4). Crystallization of the mix-
ture from ethanol gave the individual diastereomer (as
1
verified by H NMR analysis) of 25 in a yield of 74%.
The X-ray structural analysis of the appropriate single
crystal allowed us to determine its configuration as
(Rp,Sc)-25 (Figure 5). A partially resolved 7 was isolated
by hydrolysis of the mother liquor with 2 N HCl in etha-
nol. Similarly, its reaction with (R)-a-PEAM followed by
crystallisation
of
the
diastereomeric
mixture
(Rp,Rc)-/(Sp,Rc)-25 from methanol produced diastereo-
merically pure (Sp,Rc)-25 in a yield of 68%. The individu-
al enantiomers (Sp)- and (Rp)-7 were isolated in quantita-
tive yield by hydrolysis of the respective Schiff bases with
2 N HCl in ethanol. Their enantiomeric purity was estab-
lished as >99% by HPLC analysis on a Chiralpak AD-H
column (tR =15.0 min for (Rp)-7 and tR =18.3 min for
(Sp)-7).
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Aryl[2.2]paracyclophane-Based Chiral Regioisomeric Analogs of Salicyl Aldehyde
Scheme 4. Resolution of pseudo-FHPhPC 7 into its enantiomers.
Figure 5. Molecular structure of (Rp,Sc)-25.
2.3. Synthesis and Application of Chiral Phenoxy-Imine Ligands
Based on Enantiomers of iso-FHPhPC 6 and pseudo-FHPhPC 7
Finally, we present iso-FHPhPC 6 and pseudo-FHPhPC 7
as chiral building blocks for the construction of the first
representatives of chiral phenoxy-imine ligands based on
the aryl[2.2]paracyclophane backbone. During the resolu-
tion of racemic iso-FHPhPC 6 and pseudo-FHPhPC 7
only bidentate aldimines (Rp,Rc)- and (Sp,Sc)-16
(Scheme 2) and (Rp,Sc)- and (Sp,Rc)-25 (Scheme 4) could
be obtained in enantiomerically pure form. Their diaste-
reomers as well as the ligands 26 to 31 (Figure 6) were
obtained by condensation of enantiomers 6 and 7 with
the respective amino component (amines, aminoalcohols,
and diamine) followed by crystallisation of the reaction
mixtures. By this method a set of enantiomerically pure
Figure 6. Chiral phenoxy-imine ligands of aryl[2.2]paracyclophane
type obtained from enantiomers of 6 and 7 and various amino
components.
phenoxy-imine
ligands
belonging
to
an
aryl-
[2.2]paracyclophane family was obtained:
*
*
bidentate aldimines with two stereogenic sites: (Rp,Sc)-
and (Sp,Rc)-16, (Rp,Rc)- and (Sp,Sc)-25 [obtained from
(S)- or (R)-enantiomers of a-phenylethylamine (a-
PEAM)];
tridentate planar chiral aldimines: (Rp)-26 and (Rp)-27
[from ethanolamine (EA)];
tridentate diastereomeric aldimines: (Rp,Sc)- and
(Sp,Sc)-28, (Rp,Sc)- and (Sp,Sc)-29, (Rp,Sc)- and (Sp,Sc)-
*
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R. P. Zhuravsky, V. I. Rozenberg et al.
30, [from (S)-enantiomers of valinol (ValOH) or iso-
(Sp,Sc)-30 (74 and 78% ee, entries 5a, 7a), while carbinol
(S)-32 with low enantiopurity of 13 and 5%, respectively,
was obtained with the mismatched ligands (Rp,Sc)-28 and
(Rp,Sc)-30 (entries 4a, 6a). The tridentate ligand (Rp)-26
which has no additional chiral center showed medium se-
lectivity [(R)-32, 49% ee, entry 3a] comparable to that
provided by bidentate (Rp,Rc)-16.
Examination of the ligands derived from pseudo-
FHPhPC 7 has revealed trends different from those pro-
vided by 6. Thus enantiopurity of (R)-32 was practically
independent of a-PEAM configuration for both bidentate
ligands (Rp,Rc)- and (Rp,Sc)-25 (58 and 53% ee, entries 8a,
9a). In contrast to the ligands 28 and 30 derived from iso-
FHPhPC 6, both tridentate (Rp,Sc)- and (Sp,Sc)-29 possess-
ing two stereogenic sites were not so effective and led to
the formation of carbinols 32 with low ee values and op-
posite configurations [(R)-32, 20% ee, entry 11a; (S)-32,
37% ee, entry 12a].
Ethanolamine planar chiral ligand (Rp)-27 led to a
result almost equivalent to that provided by its structural
isomer (Rp)-26 derived from iso-FHPhPC, thus giving car-
binol 32 of the same configuration and enantiomeric
purity [(R)-32, 50% ee]. A comparison of entries 10a and
3a leads to the assumption that whether the aryl paracy-
clophanyl fragment is pseudo-gem or pseudo-ortho posi-
tioned is not essential in the catalysis performed by these
tridentate ligands, the chirality of which rests on the
[2.2]paracyclophane moiety only.
leucinol (iLeuOH)];
*
tetradentate “salene”, (Sp,Sc)-31 (from ethylenedia-
mine).
The aldimines 16 and 25–30 were next examined as
chiral inductors in the Et2Zn addition to benzaldehyde
and cyclohexanecarbaldehyde. The results obtained in
this work together with several previously reported
ones[22] are collected in Table 1. In a standard experi-
ment,[13] Et2Zn (2 equiv) and the aldehyde (1 equiv) were
successively added to a solution of the ligand (10 mol%)
in toluene at 08C, and the mixture was stirred at room
temperature for 15 h. Excess Et2Zn was subsequently
quenched by addition of 1 N HCl to the reaction mixture,
and after standard work up the conversion rate and enan-
tiomeric excess of the resulting secondary alcohol were
determined by GC and chiral GC analysis, respectively.
It is clear from Table 1 that in the benzaldehyde series
(entries 1a to 12a) the ligands derived from iso-FHPhPC
6 (pseudo-gem arrangement of functional groups) demon-
strate that the stereochemical result of the addition de-
pends on the nature and configuration of the imino-
moiety. Among the diastereomeric bidentate ligands de-
rived from (R)-a-PEAM, (Rp,Rc)-16 displays better selec-
tivity than the corresponding (Rp,Sc)-16, thus demonstrat-
ing a slight matched/mismatched effect in producing 1-
phenylpropanol (R)-32 (55 vs. 37% ee, entries 2a,1a).
The use of the tridentate iminoalcohol ligands 28 and
30 bearing an additional asymmetric center strongly af-
fected the enantioselectivity, providing (S)-32 with good
asymmetric yield with the matched ligands (Sp,S)-28 and
In all experiments of the benzaldehyde series (if we ex-
clude strongly mismatched (Rp,Sc)-28 and (Rp,Sc)-30, en-
tries 4a and 6a) the configuration of the resulting 1-phe-
nylpropanol 32 was governed by the configuration of the
Table 1. Enantioselective addition of diethylzinc to aldehydes catalysed by ligands 16, 25–30 (toluene, 258C, 10 mol% of L).[a]
Entry
FHPhPC
Amine
L
Carbinol 32[c]
Carbinol 33[c]
(a or b)[b]
1
2
3
4
5
6
7
8
(Rp)-6
(Rp)-6
(Rp)-6
(Rp)-6
(Sp)-6
(Rp)-6
(Sp)-6
(Rp)-7
(Rp)-7
(Rp)-7
(Rp)-7
(Sp)-7
(S)-a-PEAM
(R)-a-PEAM
EA
(S)-ValOH
(S)-ValOH
(S)- iLeuOH
(S)- iLeuOH
(S)-a-PEAM
(R)-a-PEAM
EA
(Rp,Sc)-16
(Rp,Rc)-16
(Rp)-26
(Rp,Sc)-28
(Sp,Sc)-28
(Rp,Sc)-30
(Sp,Sc)-30
(Rp,Sc)-25
(Rp,Rc)-25
(Rp)-27
37 (R)[d]
55 (R)[d]
49 (R)
13 (S)[d]
74 (S)[d]
5 (S)
34 (S)
32 (S)
25 (S)
–
31 (R)
–
78 (S)
–
58 (R)
53 (R)
50 (R)
20 (R)
37 (S)[d]
44 (S)
45 (S)
51 (S)
–
9
10
11
12
(S)-ValOH
(S)-ValOH
(Rp,Sc)-29
(Sp,Sc)-29
34 (R)
[a] The conversions were determined by GC analysis of the reaction mixtures after standard work-up (yields: 78 to 94% for 32 and near quan-
titative for 33). [b] a for benzaldehyde series, b for cyclohexanecarbaldehyde series. [c] The absolute configurations of the secondary alcohols
were determined by the elution order of chiral GC analysis in comparison with standard samples. [d] Taken from previous publications[22] for
comparison.
162
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ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Isr. J. Chem. 2012, 52, 156 – 170

Aryl[2.2]paracyclophane-Based Chiral Regioisomeric Analogs of Salicyl Aldehyde
planar chiral paracyclophanyl fragment of the ligand
[(R)-32 as governed by (Rp) ligands, entries 1a-3a, 8a-11a,
and (S)-32 as governed by (Sp) ligands, entries 5a, 7a,
12a].
The efficiency of the selected iso-FHPhPC and pseudo-
FHPhPC derived ligands was next evaluated in the reac-
tion of diethylzinc with cyclohexane 1-carbaldehyde,
which resulted in the formation of 1-cyclohexylpropanol
33. The main differences between the two aldehyde series
may be summarized as follows:
10% ee; (Rp)-pseudo-FHPC/(S)-ValOH, (S)-32, 40% ee;
(Rp)-iso-FHPC/(R)-ValOH, (R)-32, 60% ee).[20]
We believe that the phenoxy-imine ligands constructed
on the basis of a configurationally rigid and conforma-
tionally flexible backbone could find their application in
various stereoselective processes. Further development of
the FHPhPC project as well as the elaboration of other
chiral ligands based on the aryl[2.2]paracyclophane back-
bone is in progress in our research group.
i) in all cases where cyclohexane carbaldehyde was ap-
plied the carbinols 33 had opposite configurations
[(S)-33 as governed by (Rp) ligands, entries 1b-3b, 8b–
10b, and (R)-33 as governed by (Sp) ligands, entries 5b,
12b];
ii) the lower enantioselectivity was observed for both
series of iso- and pseudo-FHPhPC ligands (Table 1,
entries 1b–3b, 5b and 8b–10b, 12b). It is noteworthy
that a decrease in enantioselectivity is more evident in
the iso-FHPhPC series. Thus, for the planar and cen-
tral chiral tridentate ligand (Sp,Sc)-28, one of the most
efficient in the benzaldehyde series, the selectivity de-
creased noticeably (cf. (S)-32, 74% ee, entry 5a and
(R)-33, 31% ee, entry 5b).
4. Experimental Section
General: THF, Et2O, dioxane and toluene were distilled from
sodium benzophenone ketyl under argon before use. DMF was
distilled under reduced pressure from P2O5 and stored over mo-
lecular sieves 3 ꢀ. Benzene, heptane, hexane, ethanolamine were
distilled over Na before use. (S)- and (R)-a-phenylethylamines
were purchased from Merck; (S)-valinol, (S)-leucinol and Et2Zn
(1 N solution in hexane) were purchased from Fluka and used
without purification. Benzaldehyde and cyclohexanecarbalde-
hyde were purchased from Aldrich, stored and used under argon
without further purification. NMR: Bruker AMX-400
1
(400.13 MHz) and Bruker Avance 300 (300 MHz). The H NMR
signals of the residual protons of deuterated solvents were used
as internal standards. MS: KRATOS MS890 A (70 eV). Optical
rotations were measured with a PerkinElmer-241 polarimeter in
a thermostated cell. TLC analyses were performed on silica gel
precoated SORBFIL plates PTLC-A-UV (Sorbpolimer).
Column chromatography was performed on Kieselgel 60
(Merck). Enantiomeric and diastereomeric analyses were carried
out by HPLC on a Chiracel-AD chiral column (hexane/iPrOH=
4:1, 1 mLminÀ1). The enantioselective Et2Zn additions to benzal-
dehyde were performed according to established procedures.[13]
3. Conclusions
We elaborated efficient routes to two novel regioisomeric
chiral analogs of salicylaldehyde with an aryl-
[2.2]paracyclophane backbone, namely, 4-formyl-13-(2-hy-
droxyphenyl)-[2.2]paracyclophane (iso-FHPhPC) and 4-
formyl-12-(2-hydroxyphenyl)-[2.2]paracyclophane
(pseudo-FHPhPC), and developed techniques for their
optical resolution. These hydroxyaldehydes combined
with amines and aminoalcohols gave rise to a set of novel
enantiomerically pure bi-, tri-, and tetradentate chiral
phenoxy-imino ligands.
The majority of these compounds was tested as chiral
inductors in enantioselective Et2Zn addition to aldehydes.
They provide a low to good level of stereoselectivity of
the reaction (up to 78%) depending on the ligand archi-
tecture. On average, among [2.2]paracyclophane derived
phenoxy-imine ligands with non-classical arrangement of
4-Methoxycarbonyl-13-(2-methoxyphenyl)-[2.2]paracyclophane
11: A slurry of 10 (1.2 g, 3.476 mmol), o-anysilboronic acid
(1.058 g, 6.952 mmol), PdCl2(dppf) (0.050 g, 0.0695 mmol), and
K3PO4 (1.97 g, 9.281 mmol) in abs. toluene (12 mL) was heated
in an oil bath at 115–1208C for 30 h under argon. The reaction
mixture was cooled to room temperature, diluted with aq. NaCl
(10 mL) and THF (10 mL) and stirred for 15 min. The mixture
was extracted with THF (3ꢁ15 mL) and dried with Na2SO4.
After evaporation of the solvent in vacuo and purification of the
solid residue on SiO2 (eluent benzene) the target biaryl 11 (Rf =
0.24, 1.03 g, 80%) was isolated as well as starting material 10
(Rf =0.32, 0.180 g, 15%). An analytically pure sample of 11 was
obtained by crystallization from ethanol. M.p. 182.5–183.58C;
m.p. lit.[22] 182.5–183.58C.
4-Hydroxymethyl-13-(2-methoxyphenyl)-[2.2]paracyclophane 12:
To
a solution of 4-methoxycarbonyl-13-(2-methoxy-phenyl)-
the functional groups, a-phenylethylamine derivatives
[2.2]paracyclophane 11 (0.2 g, 0.537 mmol) in dry Et2O (30 mL)
LiAlH4 (0.122 g, 3.22 mmol) was added. The reaction mixture
was refluxed for 3 h, cooled down and hydrolyzed with an excess
of 2 N HCl solution. After extraction with Et2O (2 x 15 mL) the
combined organic fractions were successively washed with H2O
(2ꢁ20 mL), saturated aq. NaHCO3 (20 mL), H2O (15 mL) and
dried with Na2SO4. The crude 11 (0.186 g, >99%) was obtained
after removal of the solvent in vacuo. An analytically pure
sample of 11 (0.130 g, 70%) was obtained by crystallization from
toluene. M.p. 125–1278C; 1H NMR (400 MHz, CDCl3, 258C):
d=2.75–2.86 (m, 1H, -CHHCH2-); 2.92–3.09 (m, 3H, -CH2CH2-
); 3.10–3.33 (m, 4H, -CH2CH2-); 3.79 (s, 3H, -OCH3); 4.12 (d,
with iso- and pseudo-FHPhPC were less efficient than
those with the respective FHPC ligands (which led to for-
mation of 32 with ee values up to 97%; see our previous
paper[20]). At the same time the diastereomerically pure
tridentate iminoalcohol ligand derived from (Sp)-iso-
FHPhPC and (S)-ValOH was the most effective and
showed a result (74% ee) superior to all previously re-
ported ones for ligands derived from enantiomers of vali-
nol and regioisomeric FHPC 3–5 (the best results in that
series are as follows: (Rp)-FHPC/(R)-ValOH, (R)-32,
Isr. J. Chem. 2012, 52, 156 – 170
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.ijc.wiley-vch.de
163

Full Paper
R. P. Zhuravsky, V. I. Rozenberg et al.
2JH,H =13.2 Hz, 1H, -CHHOH); 4.31 (d, 2JH,H =13.2, 1H,
An analytically pure sample (0.512 g, 80%) was obtained by
crystallization from ethanol. M.p. 227–2318C (dec.); 1H NMR
(400 MHz, CDCl3, 258C): d=2.80–2.92 (m, 1H, -CHHCH2-);
3.01–3.39 (m, 6H, -CH2CH2-); 3.96–4.07 (m, 1H, -CHHCH2-);
5.40 (br. s, 1H, OH); 6.60–6.68 (m, 2H); 6.73–6.85 (m, 4H);
6.89–7.01 (m, 2H); 7.41 (d, 4JH,H =1.8 Hz, 1 H, PC-arom.-H);
3
-CHHOH); 6.48–6.55 (m, 2H, 7 and 15-H); 6.61 (d, J=7.6, 1 H,
8-H); 6.66 (br. s, 2H, 5 and 12-H); 6.74 (br. s, 1H, 16-H); 6.94
3
(d, JH,H =8.3 Hz, 1 H, 22-H); 7.05–7.13 (m, 1H, 20-H); 7.29–7.37
3
(m, 1H, 21-H); 7.47 (br d, JH,H =7.3 Hz, 1 H, 19-H); MS (EI),
m/z (rel): 326 (16, M+ÀH2O), 211 (14), 210 (48, M+ÀCH2-
C6H3(CH2OH)-CH2), 209 (100), 208 (63), 196 (18), 195 (77), 194
(17), 181 (12), 180 (12) 178 (56), 177 (15), 176 (11), 167 (18), 166
(20), 165 (54), 152 (37), 134 (10), 131 (11), 128 (10), 119 (17), 117
(12), 115 (23), 105 (52), 103 (14). Anal. calcd for C24H24O2: C,
83.69; H, 7.02. Found: C, 83.68; H, 7.11.
7.47 (br d, JH,H =7.5 Hz, 1 H); MS (EI), m/z (rel): 344 (25, M+),
3
326 (12, M+ÀH2O), 197 (16), 196 (47, M+ÀCH2-C6H3(COOH)-
CH2), 195 (84), 194 (19), 182 (25), 181 (100), 179 (21), 178 (22),
177 (11), 167 (11), 165 (23), 153 (10), 152 (25), 131 (36), 115 (11),
105 (11), 103 (15). Anal. calcd for C24H22O2: C, 80.21; H, 5.85.
Found: C, 80.02; H, 5.96.
4-Formyl-13-(2-methoxyphenyl)-[2.2]paracyclophane 13: To
a
stirred solution of 12 (0.100 g, 0.290 mmol) in anhydrous dioxane
(6 mL) a solution of DDQ (0.066 g, 0.290 mmol) in dioxane
(2.5 mL) was added dropwise at room temperature. The reaction
mixture was stirred for 3 h, the precipitated DDQH2 was filtered
off, and the solvent was removed in vacuo. The residue was puri-
fied by preparative chromatography on SiO2 (Rf =0.58; CH2Cl2)
to yield 13 (0.98 g, 98%). An analytically pure sample was ob-
tained by crystallization from ethanol (0.86 g, 86%). M.p. 140–
1418C; 1H NMR (400 MHz, CDCl3,): d=2.80–2.92 (m, 1H,
-CHHCH2-); 2.93–3.12 (m, 3H, -CH2CH2-); 3.15–3.36 (m, 3H,
-CH2CH2-); 3.68–3.86 (m, 1H, -CHHCH2-); 3.80 (s, 3H, -OCH3);
6.53–6.77 (m, 4H, PC-arom.-H); 6.84–6.95 (m, 2H, arom.-H);
7.04–7.14 (m, 2H); 7.22–7.28 (m, 1H); 7.29–7.38 (m, 1 H, arom.-
H); 9.69 (s, 1 H, CHO); MS (EI), m/z (rel): 342 (23, M+), 210
(41, M+ÀCH2-C6H3(CHO)-CH2), 209 (100), 195 (40, M+ÀCH2-
C6H3(CHO)-CH2 and CH3), 179 (26), 178 (23). Anal. calcd for
C24H22O2: C, 84.18; H, 6.48. Found: C, 84.24; H, 6.24.
4-Hydroxymethyl-13-(2-hydroxyphenyl)-[2.2]paracyclopane 15:
A suspension of 14 (0.639 g, 1.855 mmol) and LiAlH4 (0.423 g,
11.132 mmol) in dry Et2O (80 mL) was refluxed for 6 h. After
cooling, the reaction mixture was acidified with 2 N HCl, extract-
ed with Et2O (2 x 40 mL), successively washed with H2O (2ꢁ
50 mL), saturated aq. NaHCO3 (40 mL), H2O (40 mL), and dried
with Na2SO4. The solvent evaporation in vacuo yielded crude
product 14 (0.607 g, 99%). An analytically pure sample of 14
(0.455 g, 75%) was obtained by crystallization from hexane. M.p.
173–174.58C; 1H NMR (400 MHz, CDCl3,): d=2.79–2.90 (m,
1H, -CHHCH2-); 2.95–3.14 (m, 3H, -CH2CH2-); 3.15–3.35 (m,
4H, -CH2CH2-); 4.19 (d, 2JH,H =13.0, 1H, -CHHOH); 4.37 (d,
2JH,H =13.0 Hz, 1 H, -CHHOH); 5.60 (br s, 1H, OH); 6.55 (br s,
1H, PC-arom.-H); 6.59–6.75 (m, 5H, PC-arom.-H); 6.95 (dd,
3JH,H =8.1 Hz, 4JH,H =1.0 Hz, 1 H, arom.-H); 7.04–7.11 (m, 1H,
3
arom.-H); 7.26–7.32 (m, 1H, arom.-H); 7.51 (br d, JH,H =8.1 Hz,
1 H, arom.-H); MS (EI), m/z (rel): 312 (25, M+ÀH2O), 197 (15),
196 (47, M+ÀCH2-C6H3(CH2OH)-CH2), 195 (82), 194 (100), 182
(19), 181 (85), 179 (22), 178 (22), 167 (14), 165 (30), 153 (13), 152
(32), 134 (14), 128 (11). 119 (17), 118 (10), 117 (13), 115 (24), 105
(53), 104 (10). Anal. calcd for C23H22O2: C, 83.60; H, 6.71.
Found: C, 83.51; H, 6.74.
4-Formyl-13-(2-hydroxyphenyl)-[2.2]paracyclophane 6 (route A,
from 13): To a boiling solution of 13 (0.128 g, 0.374 mmol) in gla-
cial acetic acid (6 mL), HBr (6 mL of 48% aq. solution) was
added and the reaction mixture was refluxed for 3 h. After cool-
ing to room temperature, the solution was concentrated in vacuo.
The residue was dissolved in benzene (14 mL) and the solution
washed with saturated aq. Na2CO3, brine, and dried with
Na2SO4. The solvent was evaporated and the residue was puri-
fied by preparative chromatography on SiO2 (Rf =0.38; CH2Cl2),
to yield 6 (0.058 g, 47%). An analytically pure sample (0.49 g,
40%) was obtained by crystallization from ethanol. M.p. 199.5–
4-Formyl-13-(2-hydroxyphenyl)-[2.2]paracyclophane 6 (route B,
from 15): To a stirred solution of 14 (0.843 g, 2.551 mmol) in an-
hydrous dioxane (57 mL),
a solution of DDQ (0.579 g,
2.551 mmol) in dioxane (14 mL) was added dropwise at room
temperature. The reaction mixture was stirred for 3 h, the pre-
cipitated DDQH2 was filtered off, and the solvent was removed
in vacuo. The residue was purified by preparative chromatogra-
phy on SiO2 (Rf =0.38; CH2Cl2), to yield 6 (0.787 g, 94%). The
analytical data agree with those of 6, obtained by route A.
1
2028C; H NMR (400 MHz, CDCl3, 258C): d=2.86–2.96 (m, 1H,
2-H); 3.00–3.16 (m, 3H, 1-H, 9-H and 10-H); 3.20–3.37 (m, 3, 1-
H, 9-H and 10-H); 3.79–3.88 (m, 1H, 2-H); 5.42 (s, 1H, OH);
4
3
4
6.62 (d, JH,H =1.8 Hz, 1H, 5-H); 6.67 (dd, JH,H =7.8 Hz, JH,H
=
Resolution of 4-formyl-13-(2-hydroxyphenyl)-[2.2]paracyclo-
phane 6: A solution of racemic 5 (0.820 g, 2.497 mmol) and (S)-
a-PEAM (0.453 g, 0.48 mL, 3.746 mmol) in toluene (70 mL) was
refluxed in a flask equipped with a Dean–Stark trap filled with
MgSO4 for 14 h. The solvent was evaporated and the mixture of
diastereomeric aldimines (Sp,Sc)- and (Rp,Sc)-16 was successively
crystallized from a 5:4 mixture of hexane/toluene (90 mL) and
ethanol (70 mL) to give aldimine (Sp,Sc)-16 (0.313 g, 58%, de>
1.8 Hz, 1 H, 7-H); 6.73 (d, 3JH,H =7.8 Hz, 1 H, 15-H); 6.80 (d,
3JH,H =7.9 Hz, 1 H, 8-H); 6.92 (br.d, 2 H, 16-H and 22-H); 7.07
4
(m, 1H, 21-H); 7.12 (d, JH,H =1.8 Hz, 1H, 12-H); 7.25–7.34 (m,
2H, 19-H and 20-H); 9.75 (s, 1 H, CHO); MS (EI), m/z (rel):
328 (70, M+), 327 (22), 197 (29), 196 (83, M+ÀCH2-C6H3(CHO)-
CH2), 195 (100), 194 (42), 182 (49), 181 (99), 179 (41), 178 (47),
176 (17), 167 (28), 166 (18), 165 (47), 164 (11), 153 (23), 152 (49),
151 (15), 139 (13), 133 (23), 132 (13), 131 (15), 128 (14), 127 (10),
115 (22), 105 (15), 102 (11). Anal. calcd for C23H20O2: C, 84.12;
H, 6.14. Found: C, 83.96; H, 6.01.
1
20
98% by H NMR analysis). [a]D +100.3 (c 0.60, benzene); m.p.
1
217–2198C; H NMR (400 MHz, [D6]DMSO, 258C): d=1.36 (d,
3JH,H =6.7 Hz, 3 H, CH3); 2.62–2.73 (m, 1H, -CHHCH2-); 2.74–
2.85 (m, 1H, -CHHCH2-); 2.91–3.04 (m, 3H, -CH2CH2-); 3.06–
3.23 (m, 2H, -CH2CH2-); 3.63–3.74(m, 1H, -CHHCH2-); 4.03 (q,
13-(2-Hydroxyphenyl)-4-carboxy[2.2]paracyclophane 14: A mix-
ture of 11 (0.700 g, 1.87 mmol) and glacial acetic acid (35 mL)
was stirred at 908C until a clear solution was obtained (nearly
0.5 h). It was added to a hot aq. solution of 48% HBr (30 mL)
and the mixture was refluxed for 3.5 h. After cooling the solvent
was evaporated in vacuo, the residue was dissolved in CH2Cl2
(50 mL), washed with H2O (4 x 30 mL) and dried with Na2SO4.
The crude product was passed through a SiO2 filled column
(eluent CH2Cl2) to yield 14 (0.640 g, 99%), Rf =0.48 (AcOEt).
3JH,H =6.7 Hz, 1H, 23-H); 6.50 (dd, JH,H =7.8 Hz, JH,H =1.8 Hz,
1H, 7-H or 16-H); 6.56–6.62 (m, 2H, 5-H and C8-H or 12-H and
15-H); 6.64 (d, 3JH,H =7.8 Hz, 1H, 15-H or 8-H); 6.70–6.79 (m,
2H, 16-H or 7-H and 22-H); 6.85–6.92 (m, 2H, 12-H or 5-H and
20-H); 6.94–7.01 (m, 2H, 24-H and 28-H); 7.02–7.09 (m, 1, 21-
H); 7.13–7.27 (m, 3H, 25-H, 26-H and 27-H); 7.31–7.40 (m, 1H,
19-H); 8.07 (s, 1H, CH=N); 9.11 (s, 1H, OH); MS (EI), m/z
3
4
164
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ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Isr. J. Chem. 2012, 52, 156 – 170

Aryl[2.2]paracyclophane-Based Chiral Regioisomeric Analogs of Salicyl Aldehyde
(rel): 431 (46, M+), 327 (19); 326 (41, M+ÀCH3CH-C6H5); 311
(20, M+ÀCH3CHN-C6H5); 235 (20, M+ÀCH2-C6H3(C6H5OH)-
CH2); 234 (53); 196 (20), 195 (41), 194 (20), 181(60); 179 (13);
178 (21); 177 (11); 165 (26); 152 (24); 144 (16); 143 (28); 132
(33);131 (79); 130 (99); 129 (22); 115 (20); 106 (56); 105 (100);
104 (33); 103 (45). Anal. calcd for C31H29NO: C, 86.27; H, 6.77;
N, 3.25. Found: C, 86.17; H, 6.71; N, 3.24.
À788C under argon, nBuLi (0.28 mL of 3.27m solution in
hexane, 0.915 mmol, 1.2 equiv) was added dropwise via syringe.
The reaction mixture was stirred for 4 h at À788C and N-formyl-
piperidine (0.207 g, 0.20 mL, 1.83 mmol) was added. The reaction
mixture was stirred for further 1 h at À788C and warmed to
room temperature overnight. The crude reaction mixture was di-
luted with toluene (15 mL) and THF (10 mL) and quenched with
2 N HCl (15 mL). The organic material was extracted with a 3:2
mixture of toluene and THF (3ꢁ15 mL) and CH2Cl2 (2ꢁ15 mL),
and dried with Na2SO4. The solvent was evaporated in vacuo and
the residue was purified by preparative chromatography on SiO2.
From combined fractions with Rf =0.47 (benzene) 4-(2-methoxy-
phenyl)-[2.2]paracyclo-phane 22 (0.091 g, 38%) was isolated. An
analytically pure sample was obtained by crystallization from
Compound (Sp,Sc)-16 was hydrolyzed by reflux with 2 N HCl for
3 h (4 mL) in ethanol (35 mL). After dilution of the reaction
mixture with H2O (40 mL), the organic material was extracted
with CH2Cl2 (4ꢁ20 mL) and dried with Na2SO4. Solvent removal
20
gave (Sp)-6 (0.234 g, 57%) as a white powder. [a]D +65.6 (c
0.36, benzene); m.p. 213–2178C (dec.); Anal. calcd for C23H20O2:
C, 84.12; H, 6.14. Found: C, 83.94; H, 6.12.
1
hexane. M.p. 104–1068C; H NMR (300 MHz, CDCl3, 258C): d=
2.73–2.92 (m, 2H, -CH2CH2-); 2.94–3.24 (m, 6H, -CH2CH2-);
3.77 (s, 3H, -OCH3); 6.46–6.72 (m, 7 H, PC-arom.-H); 6.97 (br.
d, 3JH,H =8.3 Hz, 1 H, arom.-H); 7.14–7.22 (m, 1 H, arom.-H);
7.34–7.43 (m, 1 H, arom.-H); 7.58 (br. d, 3JH,H =7.5 Hz, 1H,
arom.-H); MS (EI), m/z (rel): 314 (30, M+), 210 (23, M+ÀCH2-
C6H4-CH2), 209 (100), 195 (77, M+ÀCH2-C6H4-CH2 and CH3),
194(16), 179 (13), 178 (17), 165 (13). Anal. calcd for C23H22O: C,
87.86; H, 7.05. Found: C, 87.84; H, 6.98.
The combined ethanol filtrates, containing partially resolved
(Rp,Sc)-16, after evaporation and hydrolysis, gave partially re-
solved (Rp)-6 (0.576 g, 1.752 mmol). The condensation of this
compound with (R)-a-PEAM (0.318 g, 0.33 mL, 2.628 mmol)
after two successive crystallizations of the reaction mixture from
a 5:4 mixture of hexane/toluene and from ethanol afforded
20
(Rp,Rc)-16 (0.290 g, 54%). [a]D À100.8 (c 0.97, benzene); m.p.
214.5–215.58C. Anal. calcd for C31H29NO: C, 86.27; H, 6.77; N,
3.25. Found: C, 86.16; H, 6.79; N, 3.17.
From the combined fractions with Rf =0.22 (benzene), com-
pound 21 (0.157 g, 60%) was obtained. M.p. 166–168.58C;
1H NMR (400 MHz, CDCl3, 258C) d=2.55–2.66 (m, 1H,
-CH2CHH-); 2.84–3.07 (m, 4H, -CH2CH2-); 3.18–3.28 (m, 1H,
-CH2CHH-); 3.33–3.42 (m, 1H, -CH2CHH-); 3.72 (s, 3H, -CH3);
20
Hydrolysis of (Rp,Rc)-16 gave (Rp)-6 (0.219 g, 53%). [a]D À63.6
(c 0.36, benzene); m.p. 215–217.58C (dec); Anal. calcd for
C23H20O2: C, 84.12; H, 6.14. Found: C, 83.07; H, 6.09.
4
The enantiomeric purity of (Rp)- and (Sp)-6 was determined as
>99% by Chiral HPLC analysis (Chiralpak AD-H column,
254 nm, 1 mLminÀ1, 9:1 mixture of hexane and 2-propanol, tR =
22.2 min for (Sp)-6 and tR =26.4 min for (Rp)-6).
4.09–4.17 (m, 1H, -CH2CHH-); 6.40 (d, JH,H =1.8, 1 H, 13-H);
3
3
4
6.56 (d, JH,H =7.8 Hz, 1 H, 22-H); 6.61 (dd, JH,H =7.8 Hz, JH,H
=
3
1.8 Hz, 1 H, 15-H); 6.78 (d, JH,H =7.8 Hz, 1 H, 8-H); 6.85 (dd,
3JH,H =7.8, JH,H =1.8 Hz, 1 H, 7)-H; 6.94 (br. d, JH,H =8.3 Hz, 1
4
3
4
H, 22-H); 7.17–7.22 (m, 1 H, 20-H); 7.23 (d, JH,H =1.8 Hz, 1 H,
5-H); 7.33–7.40 (m, 1, 21-H); 7.42–7.47 (dd, JH,H =7.6 Hz, JH,H
4-Bromo-12-(2-methoxyphenyl)[2.2]paracyclophane 19: A sus-
pension of dibromide 18 (0.4 g, 1.093 mmol), o-anisylboronic
acid (0.498 g, 3.279 mmol), PdCl2(dppf) (0.016 g, 0.022 mmol)
and K3PO4 (0.927 g, 4.371 mmol) in abs. toluene (4 mL) was
stirred for 30 h at 115–1258C under argon. After cooling, the re-
action mixture was quenched with toluene (10 mL) and 1 N
NaOH (10 mL). After extraction with THF, washing the solution
with 20% aq. NaCl, drying with Na2SO4 and solvent evaporation
in vacuo, the crude product was purified by preparative column
chromatography on SiO2 (eluent CCl4). From combined fractions
with Rf =0.1 19[21] (0.222 g, 52%) was obtained. An analytically
pure sample (0.186 g, 44%) was prepared by crystallization from
hexane.
3
4
=
1.6 Hz, 1 H, 19-H); 10.13 (s, 1H, CHO); MS (EI), m/z (rel): 342
(20, M+), 327 (13, M+ÀCH3); 325 (11), 324 (22), 210 (35, M+
ÀCH2-C6H3(CHO)-CH2), 209 (100), 197 (11), 196 (55), 195 (77,
M+ÀCH2-C6H3(CHO)-CH2 and CH3), 194(23), 181 (14), 179
(24), 178 (34), 177 (11), 167 (17), 166 (13), 165 (28), 152 (20), 149
(10). Anal. calcd for C24H22O2: C, 84.18; H, 6.48. Found: C,
84.29; H, 6.57.
4-Formyl-12-(2-hydroxyphenyl)-[2.2]paracyclophane 7 (route A,
from 21): To a boiling solution of 21 (0.113 g, 0.330 mmol) in gla-
cial acetic acid (2 mL) HBr (2 mL of 48% aq. solution) was
added, and the resulting mixture was refluxed for 2 h. After cool-
ing to room temperature the solution was concentrated in vacuo,
the residue was dissolved in benzene (12 mL) and the solution
was successively washed with saturated aq. Na2CO3, brine, and fi-
nally dried with Na2SO4. The solvent was evaporated and the res-
idue was purified by preparative chromatography on SiO2 (Rf =
0.43; CH2Cl2) to yield 7 (0.033 g, 30%). An analytically pure
sample (0.20 g, 18%) was obtained by crystallization from a 2:1
From combined fractions with Rf =0.09 (CCl4) the 4,12-bis(2-me-
thoxyphenyl)-[2.2]paracyclophane 20 (0.171 g, 37%) was isolat-
ed. An analytically pure sample (0.14 g, 30%) was obtained by
crystallization from Et2O. M.p. 159.5–160.58C; 1H NMR
(400 MHz, CDCl3, 258C) d=2.59–2.69 (m, 2H, -CH2CH2-); 2.83–
2.93 (m, 2H, -CH2CH2-); 3.06–3.20 (m, 4H, -CH2CH2-); 3.36 (s,
6H, OCH3); 6.64–6.70 (m, 4 H, 5-H, 7-H, 13-H and 16-H); 6.75
1
mixture of hexane/toluene. M.p. 97–1008C; H NMR (400 MHz,
3
3
(d, JH,H =7.8 Hz, 2 H, 8-H and 15-H); 6.93 (d, JH,H =8.1 Hz, 2
CDCl3, 258C): d=2.60–2.71 (m, 1H, 9-H); 2.88–3.10 (m, 4H, 1-
H, 2-H, 9-H and 10-H); 3.25–3.34 (m, 1H, 1-H); 3.35–3.44 (m,
1H, 2-H); 4.09–4.19 (m, 1H, 10-H); 5.81 (s, 1H, OH); 6.44 (d,
4JH,H =1.8 Hz, 1H, 13-H); 6.64–6.71 (m, 2H, 5-H and 16-H); 6.79
(d, 3JH,H =7.8, 1 H, 7-H); 6.85 (dd, 3JH,H =7.8 Hz, 4JH,H =1.8 Hz,
H, 22-H and 28-H); 7.00–7.07 (m, 2 H, 21-H and 27-H); 7.30–
7.37 (m, 2 H, 20-H and 26-H); 7.60 (dd, 3JH,H =7.8 Hz, JH,H
=
4
1.6 Hz, 2 H, 19-H and 25-H); MS m/z (%): 421 (10, M+), 420
(30, M+), 212 (17), 211 (100), 210 (54), 209 (79), 196 (32), 195
(82), 194 (15), 181 (11), 180 (12), 179 (59), 178 (48), 177 (14), 167
(14), 166 (11), 165 (40), 152 (25). Anal. calcd for C30H28O2: C,
85.68; H, 6.71. Found: C, 85.71; H, 6.75.
3
4
1H, 15-H); 6.95 (dd, JH,H =8.1 Hz, JH,H =1.1, 1H, 22-H); 7.12–
7.21 (m, 1H, 21-H); 7.23–7.33 (m, 2H, 8-H and 20)-H); 7.44 (dd,
3JH,H =7.7, 4JH,H =1.6 Hz, 1H, 19-H); 10.14 (s, 1H, CHO); MS
(EI), m/z (rel): 328 (11, M+), 310 (11, M+ÀH2O), 196 (21, M+
ÀCH2-C6H3(CHO)-CH2-), 195 (46), 182 (16), 181 (100), 167 (10),
4-Formyl-12-(2-methoxyphenyl)-[2.2]paracyclophane 21: To
stirred solution of 19 (0.300 g, 0.763 mmol) in THF (4.5 mL) at
a
Isr. J. Chem. 2012, 52, 156 – 170
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.ijc.wiley-vch.de
165

Full Paper
R. P. Zhuravsky, V. I. Rozenberg et al.
165 (11), 152 (14). Anal. calcd for C23H22O2: C, 84.12; H, 6.14.
Found: C, 84.11; H, 6.15.
lized from methanol (70 mL) to give imine (Rp,Sc)-25 (0.663 g,
1
20
74%, de>98% by H NMR analysis). [a]D +179.1 (c 0.67, ben-
1
zene); m.p. 55–568C; H NMR (300 MHz, C6D6, 258C): d=1.79
3
4-Formyl-12-bromo[2.2]paracyclophane 23: To a stirred solution
of 18 (2.500 g, 6.831 mmol) in THF (38 mL) at À788C under
argon, nBuLi (2.51 mL of 3.27m solution in hexane, 8.20 mmol,
1.2 equiv) was added dropwise via syringe. The reaction mixture
was stirred for 4 h at À788C and N-formylpiperidine (1.855 g,
1.84 mL, 16.339 mmol) was added. After complete addition, the
reaction mixture was stirred for 1 h at À788C and warmed to
room temperature overnight. The crude reaction mixture was di-
luted with toluene (60 mL) and THF (40 mL) and quenched with
2 N HCl (50 mL). The organic material was successively extract-
ed with a 3:2 mixture of toluene and THF (3ꢁ50 mL) and
CH2Cl2 (2ꢁ60 mL), and dried with Na2SO4. The solvent was
evaporated in vacuo and the residue was purified chromatogra-
phy on SiO2 (Rf =0.40; benzene), to yield compound 23[22]
(1.380 g, 64%).
(d, JH,H =6.6 Hz, 3H, CH3); 2.44–2.79 (m, 5H, -CH2CH2-); 3.02–
3.15 (m, 1H, -CHHCH2-); 3.29–3.43 (m, 1H, -CHHCH2-); 3.65–
3
3.80 (m, 1H, -CHHCH2-); 4.56 (q, JH,H =6.6 Hz, 1 H, 23-H); 6.0
(br. s, 1H, OH); 6.41–6.46 (m, 2H, 7-H and 8-H, or 15-H and 16-
H); 6.49 (dd, 3JH,H =7.8 Hz, 4JH,H =1.8 Hz, 1 H, 7-H or 15-H);
6.51–6.58 (m, 2 H, 8-H or 16-H and 13-H); 7.02–7.11 (m, 1 H,
arom-H); 7.18–7.35 (m, 3 H, arom-H); 7.36–7.45 (m, 2H, 25-H
4
and 27-H); 7.66 (d, JH,H =1.8, 1 H, 5-H); 7.68–7.74 (m, 2 H, 24-
H and 28-H); 7.90–7.99 (m, 1H, arom-H); 8.44 (s, 1H, CH=N);
MS (EI), m/z (rel): 431 (92, M+), 327 (32), 326 (63, M+
ÀCH3CH-C6H5), 311 (28, M+ÀCH3CHN-C6H5), 310 (73), 309
(28), 295 (18), 293 (12), 250 (14), 236 (29), 235 (27, M+ÀCH2-
C6H3(C6H5OH)-CH2), 234 (53), 196 (15), 195 (46), 182 (19), 181
(72), 178 (13), 167 (14), 165 (20), 152 (23), 144 (13), 132 (37), 131
(69), 130 (100), 129 (13), 115 (12), 105 (61). Anal. calcd for
C31H29NO: C, 86.27; H, 6.77; N, 3.25. Found: C, 86.28; H, 6.84;
N, 3.17.
4-Formyl-12-(2-oxymethylenemethoxyphenyl)-[2.2]paracyclo-
phane 24: A suspension of bromide 23 (1.800 g, 5.71 mmol), o-
anisylboronic acid (1.560 g, 8.57 mmol), Pd(dppf)Cl2 (0.041 g,
0.057 mmol, 1 mol%) and K3PO4 (2.430 g, 11.42 mmol) in tolu-
ene (34 mL) under argon was stirred at reflux for 10 h. Then, a
fresh portion of o-anisylboronic acid (0.520 g, 2.86 mmol) and
K3PO4 (0.810 g, 3.81 mmol) were added and the reaction mixture
was refluxed for an additional 10 h. After cooling down to room
temperature, the reaction mixture was diluted with toluene
(20 mL) and THF (30 mL) and hydrolyzed with brine (60 mL).
The organic material was extracted with a 3:2 mixture of toluene
and THF (3ꢁ50 mL) and dried with Na2SO4. The solution was
concentrated in vacuo and purified by preparative chromatogra-
phy on SiO2. Elution with benzene (Rf =0.08) gave compound 24
(1.850 g, 87%). M.p. 100–1018C; 1H NMR (400 MHz, C6D6,
258C): d=2.51–2.61 (m, 1H, -CHHCH2-); 2.63–2.91 (m, 4H,
-CH2CH2-); 3.08–3.18 (m, 4H, -CHHCH2- and OCH3); 3.42–3.52
(m, 1H, -CHHCH2-); 3.89–4.00 (m, 1H, -CHHCH2-); 4.78 (d,
2JH,H =10.8 Hz, 1H, -OCHHO-); 4.80 (d, 2JH,H =10.8, 1H,
-OCHHO-); 6.42 (dd, 3JH,H =7.8 Hz, 4JH,H =1.8 Hz, 1H, 15-H);
Compound (Rp,Sc)-25 was hydrolyzed by refluxing it with aq. 2 N
HCl (6 mL) in ethanol (56 mL) for 4 h. After dilution of the re-
action mixture with H2O (50 mL), the organic material was ex-
tracted with CH2Cl2 (4ꢁ40 mL) and dried with Na2SO4. After
solvent evaporation, (Rp)-7 (0.499 g, 73%) was obtained as a
20
white powder. [a]D +189.3 (c 0.56, benzene); m.p. 146.5–
147.58C. Anal. calcd for C23H20O2: C, 84.12; H, 6.14. Found: C,
84.04; H, 6.09.
The combined ethanol filtrates, containing partially resolved
(Sp,Sc)-25 after evaporation and hydrolysis gave a partially re-
solved (Sp)-7 (0.882 g, 2.686 mmol), which in turn was treated
with (R)-a-PEAM (0.487 g, 0.51 mL, 4.028 mmol). The diastereo-
merically pure (Sp,Rc)-25 (0.608 g, 68%, de>98% by 1H NMR
20
analysis) was obtained by crystallization from methanol. [a]D
À177.0 (c 0.50, benzene); m.p. 63–658C. Anal. calcd for
C31H29NO: C, 86.27; H, 6.77; N, 3.25. Found: C, 86.46; H, 6.96;
N, 3.23.
3
3
6.47 (d, JH,H =7.8 Hz, 1H, 16-H); 6.52 (d, JH,H =7.8 Hz, 1H, 8-
H); 6.56 (dd, 3JH,H =7.8 Hz, 4JH,H =1.8 Hz, 1H, 7-H); 6.59 (d,
4JH,H =1.8 Hz, 1H, 13-H); 7.27–7.34 (m, 2H, 21-H and 22-H);
20
Hydrolysis of (Sp,Rc)-25 gave (Sp)-7 (0.458 g, 67%). [a]D À187.8
(c 0.47, benzene); m.p. 141.5–144.58C. Anal. calcd for C23H20O2:
C, 84.12; H, 6.14. Found: C, 84.32; H, 6.18.
4
7.38–7.47 (m, 1H, 20-H); 7.50 (d, JH,H =1.8 Hz, 1H, 5-H); 7.95
3
(br. d, JH,H =7.3 Hz, 1H, 19-H); 10.16 (s, 1H, CHO); MS (EI),
The enantiomeric purity of (Rp)-7 and (Sp)-7 was determined as
>99% by Chiral HPLC analysis (Chiralpak AD-H column;
254 nm, 1 mLminÀ1, 9:1 mixture of hexane and 2-propanol; tR =
15.0 min for (Rp)-7 and tR =18.3 min for (Sp)-7).
m/z (rel): 372 (17, M+), 340 (12, M+ÀOCH3), 240 (13, M+
ÀCH2-C6H3(CHO)-CH2-); 239 (27); 209 (11); 208 (25); 207 (10);
198 (21); 196 (21); 195 (92); 194 (63); 182 (17); 181 (80); 178
(13); 177 (12); 167 (11); 166 (11); 165 (39); 152 (22); 104 (13).
Anal. calcd for C25H24O3: C, 80.62; H, 6.49. Found: C, 80.68; H,
6.57.
General procedure for preparation of aldimines from 6 and 7
Aldimine (Sp,Rc)-16: Compound (Sp)-6 (0.050 g, 0.152 mmol) was
dissolved in absolute toluene (15 mL) and (R)-a-PEAM (0.028 g,
0.03 mL, 0.228 mmol, 1.5 equiv) was added. The solution was re-
fluxed in an apparatus equipped with a Dean–Stark trap filled
with anhydrous MgSO4 for 14 h. After solvent removal the re-
sulting solid was purified by crystallisation from 1:3 mixture of
4-Formyl-12-(2-hydroxyphenyl)-[2.2]paracyclophane 7 (route B,
from 24): To a stirred solution of 24 (1.700 g, 4.964 mmol) in
methanol (150 mL) four drops of concentrated HCl were added
at 608C and the mixture was refluxed for 4.5 h. After methanol
removal the residue was dissolved in CH2Cl2 and passed through
a SiO2 filled column. The target product 6 (1.350 g, 90%) was
obtained as a white crystalline compound. The analytical data
are in agreement with those of 7, obtained by route A.
20
toluene and hexane to yield (Sp,Rc)-16 (0.045 g, 68%). [a]D
1
+95.0 (c 0.70, benzene); m.p. 143.5–1458C; H NMR (400 MHz,
C6D6, 258C): d=1.31 (d, JH,H =6.5 Hz, 3H, CH3); 2.61–2.73 (m,
3
1H, -CHHCH2-); 2.74–2.87 (m, 2H, -CH2CH2-); 2.87–3.18 (m,
3H, -CH2CH2-); 3.21–3.34 (m, 1H, -CHHCH2-); 4.07–4.18 (m,
1H, -CHHCH2-); 4.23 (q, 3JH,H =6.5, 1H,=N-CH); 6.43 (dd,
3JH,H =7.8 Hz, 4JH,H =1.8 Hz, 1 H, PC-arom.-H); 6.48–6.56 (m,
2H, PC-arom.-H); 6.58 (dd, 3JH,H =7.8 Hz, 4JH,H =1.8 Hz, 1 H,
PC-arom.-H); 6.66 (br. s, 1H, OH); 6.69–6.77 (m, 1H, arom.-H);
6.97 (br. s, 1H, PC-arom.-H); 7.09–7.34 (m, 4 H); 7.35 (m, 3 H);
Resolution of 4-formyl-12-(2-hydroxyphenyl)-[2.2]para-cyclo-
phane 7: A solution of racemic 7 (1.363 g, 4.150 mmol) and (S)-
a-PEAM (0.753 g, 0.79 mL, 6.223 mmol) in toluene (60 mL) was
refluxed in a flask equipped with a Dean–Stark trap filled with
MgSO4 for 20 h. The solvent was evaporated and the mixture of
the diastereomeric aldimines (Rp,Sc)- and (Sp,Sc)-25 was crystal-
166
www.ijc.wiley-vch.de
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Isr. J. Chem. 2012, 52, 156 – 170

Aryl[2.2]paracyclophane-Based Chiral Regioisomeric Analogs of Salicyl Aldehyde
3
7.66 (d, JH,H =7.5 Hz, 2H, 24-H and 28-H); 8.10 (s, 1H, -CH=
C6H3(CH=NCH2CH2OH)-CH2), 195 (27), 181 (45), 175 (46, M+
ÀCH2-C6H3(C6H5OH)-CH2), 174 (100), 165 (12), 152 (12), 144
(34), 143 (16), 131 (17), 130 (32), 115 (13). Anal. calcd for
C25H25NO2: C, 80.83; H, 6.78; N, 3.77. Found: C, 80.88; H, 6.90;
N, 3.65.
N); 1H NMR (400 MHz, [D6]DMSO, 258C): d=1.35 (d, JH,H
6.3 Hz, 3 H, CH3); 2.61–2.73 (m, 1H, 2-H); 2.73–2.86 (m, 1H, 1-
H); 2.89–3.04 (m, 3H, 1-H, 9-H and 10-H); 3.06–3.21 (m, 2H, 9-
H and 10-H); 3.62–3.75 (m, 1H, 2-H); 4.03 (q, JH,H =6.3 Hz, 1H,
23-H); 6.50 (d, JH,H =7.6 Hz, 1H, 15-H); 6.55–6.62 (m, 2H, 12-H
and 16-H); 6.64 (d, JH,H =7.6 Hz, 1H, 8-H); 6.69–6.79 (m, 2H, 7-
H and 22-H); 6.83–6.92 (m, 2H, C5-H and 20-H); 6.97 (d, JH,H
7.3 Hz, 2H, 24-H and 28-H); 7.01–7.09 (m, 1H, 21-H); 7.12–7.26
(m, 3H, 25-H, 26-H and 27-H); 7.35 (br. d, JH,H =7.3 Hz, 1H,)-
H); 8.07 (s, 1H, CH=N); 9.11 (s, 1H, OH); MS (EI), m/z (rel):
431 (28, M+), 430 (13), 416 (23), 327 (22), 326 (72, M+ÀCH3CH-
C6H5), 312 (15), 311 (24, M+ÀCH3CHN-C6H5), 235 (18, M+
ÀCH2-C6H3(C6H5OH)-CH2), 234 (54), 196 (12), 195 (34), 194
(13), 185 (16), 181 (50), 178 (10), 167 (11), 165 (10), 152 (17), 149
(35), 144 (13), 143 (14), 132 (16), 131 (31), 130 (100), 129 (12),
106 (36), 105 (50), 103 (22). Anal. calcd for C31H29NO: C, 86.27;
H, 6.77; N, 3.25. Found: C, 86.44; H, 6.91; N, 3.28.
=
3
3
3
Aldimine (Rp)-27 (0.048 g, 70%) was obtained from (Rp)-7
(0.060 g, 0.183 mmol) and EA (0.017 g, 0.017 mL, 0.274 mmol)
after reflux for 12 h and crystallisation from a 3:2 mixture of tol-
3
3
=
20
uene and hexane. [a]D +124.5 (c 0.47, benzene); m.p. 153.5–
3
1
157.58C; H NMR (400 MHz, C6D6, 258C): d=2.50–2.81 (m, 5H,
-CH2CH2-); 3.01–3.14 (m, 1H, -CHHCH2-); 3.34–3.43 (m, 1H,
-CHHCH2-); 3.51–3.69 (m, 2H, 23-H and -CHHCH2-); 3.71–3.81
(m, 1H, 23-H); 3.87–3.95 (m, 1H, 24-H); 3.96–4.05 (m, 1H, 24-
H); 6.40–6.58 (m, 4H, 7-H, 8-H, 15-H and 16-H); 6.81 (br. s, 1
H, 13-H); 7.23–7.38 (m, 4H, 19-H, 20-H, 21-H and 22-H); 7.65
(br. s, 1 H, 5-H); 8.07 (br. s, 1 H, -C6H4OH); 8.31 (s, 1H, CH=
N); MS (EI), m/z (rel): 371 (77, M+), 354 (19), 311 (37), 310
(68), 309 (23), 295 (19), 293 (12), 196 (8, M+ÀCH2-
C6H3(CH=NCH2CH2OH)-CH2), 195 (22), 181 (52), 178 (12), 177
(21), 176 (81), 175 (76, M+ÀCH2-C6H3(C6H5OH)-CH2), 174
(100), 165 (17), 152 (21), 144 (65), 143 (17), 131 (20), 130 (30),
129 (14), 128 (11), 115 (17). Anal. calcd for C25H25NO2: C, 80.83;
H, 6.78; N, 3.77. Found: C, 80.64; H, 6.77; N, 3.73.
Aldimine (Rp,Sc)-16 (0.067 g, 72%) was obtained from (Rp)-6
(0.070 g, 0.213 mmol) and (S)-a-PEAM (0.039 g, 0.04 mL,
0.319 mmol, 1.5 equiv) after reflux for 14 h and crystallisation
20
from a 1:3 mixture of toluene and hexane. [a]D À93.0 (c 0.67,
benzene); m.p. 141.5–143.58C. Anal. calcd for C31H29NO: C,
86.27; H, 6.77; N, 3.25. Found: C, 86.37; H, 6.96; N, 3.16.
Aldimine (Rp,Sc)-28 (0.057 g, 75%) was obtained from (Rp)-6
(0.060 g, 0.183 mmol) and (S)-2-amino-3-methyl-1-buthanol ((S)-
ValOH) (0.033 g, 0.320 mmol) after reflux for 18 h and crystalli-
Aldimine (Rp,Rc)-25 (0.041 g, 52%) was obtained from (Rp)-7
(0.06 g, 0.183 mmol) and (R)-a-PEAM (0.033 g, 0.035 mL,
0.274 mmol) after reflux for 14 h and crystallisation from a 1:3
20
sation from a mixture of toluene and hexane. [a]D +28.4 (c
mixture of toluene and hexane. [a]D +33.9 (c 0.47, benzene);
0.37, THF); m.p. 219–2228C; 1H NMR (400 MHz, [D6]DMSO,
20
m.p. 155–1588C, 1H NMR (400 MHz, C6D6, 258C): d=1.88 (d,
3JH,H =6.7 Hz, 3H, CH3); 2.48–2.58 (m, 1H, -CHHCH2-); 2.59–
2.77 (m, 4H, -CH2CH2-); 3.07–3.17 (m, 1H, -CHHCH2-); 3.34–
3.43 (m, 1H, -CHHCH2-); 3.60–3.70 (m, 1H, -CHHCH2-); 4.54
258C): d=0.54 (d, 3JH,H =6.7 Hz, 3H, CH3); 0.66 (d, JH,H
=
3
6.7 Hz, 3H, CH3); 1.18–1.32 (m, 1H, 25-H); 2.43–2.53 (m, 1H,
23-H); 2.63–2.75 (m, 1H, 24-H); 2.85–3.07 (m, 4H, -CH2CH2-
and 24-H); 3.08–3.22 (m, 3H, -CH2CH2-); 4.00–4.12 (m, 1H,
3
3
(q, J=6.7 Hz, 1 H, 23-H); 6.46 (br. s, 2H, 7-H and 8H, or 15-H
-CHHCH2-); 4.26–4.36 (m, 1H, -CHHCH2-); 6.48 (dd, JH,H
=
3
4
4
and 16-H); 6.49 (dd, JH,H =7.8 Hz, JH,H =1.8 Hz, 1 H, 7-H or 15-
7.8 Hz, JH,H =1.8 Hz, 1H, 7-H or 16-H); 6.56–6.74 (m, 5H, 5-H,
8-H, 12-H, 15-H, and 16-H or 7-H); 6.75–6.84 (m, 1H, 19-H or
22-H); 6.87–6.97 (m, 1H, 20-H or 21-H); 7.05–7.15 (m, 1H, 21-H
or 20-H); 7.34–7.45 (m, 1H, 22-H or 19-H); 7.88 (s, 1H, CH=
N); 9.15 (s, 1H, OH); MS (EI), m/z (rel): 413 (100, M+), 412
(11), 396 (16, M+ÀH2O), 382 (23), 312 (12), 311 (60), 310 (54),
309 (18), 295 (15), 232 (24), 219 (30), 218 (84), 217 (83, M+
ÀCH2-C6H3(C6H5OH)-CH2), 216 (72), 196 (19, CH2-C6H3-
(CH=NCH(iPr)CH2OH)-CH2), 186 (34), 182 (10), 181 (43), 178
(10), 174 (21), 165 (13), 152 (14), 144 (12), 143 (14), 132 (18), 131
(50), 130 (61), 129 (15), 128 (11), 115 (11). Anal. calcd for
C28H31NO2: C, 81.32; H, 7.56; N, 3.39. Found: C, 81.44; H, 7.41;
N, 3.34.
3
H); 6.55 (d, JH,H =7.8 Hz, 1 H, 8-H or 16-H); 6.69 (br. s, 1H, 13-
H); 7.27–7.44 (m, 7H, 19-H, 20-H, 21H, 22-H, 25-H, 26-H, 27-
3
H); 7.73 (d, JH,H =7.3 Hz, 2 H, 24-H and 28-H); 7.77 (br. s, 1H,
5-H); 8.39 (br. s, 2H, CH=N and OH); MS (EI), m/z (rel): 431
(13, M+), 430 (13), 326 (5, M+ÀCH3CH-C6H5), 311 (4, M+
ÀCH3CHN-C6H5), 310 (8), 239 (5), 235 (5, M+ÀCH2-
C6H3(C6H5OH)-CH2), 234 (6), 231 (6), 209 (13), 208 (10), 194
(15), 185 (10), 181 (16), 169 (13), 167 (12), 165 (12), 155 (11), 152
(10), 149 (100), 141 (14), 139 (16), 137 (13), 131 (22), 130 (18),
127 (13), 125 (17), 121 (14), 119(13), 115 (10), 113 (22), 111 (26),
110 (10), 109 (17), 106 (15), 105 (43), 104 (11). Anal. calcd for
C31H29NO: C, 86.27; H, 6.77; N, 3.25. Found: C, 86.56; H, 7.00;
N, 3.33.
Aldimine (Sp,Sc)-28 (0.070 g, 80%) was obtained from (Sp)-6
(0.070 g, 0.213 mmol) and (S)-ValOH (0.033 g, 0.320 mmol) after
reflux for 14 h and crystallisation from a 4:1 mixture of toluene
Aldimine (Rp)-26 (0.064 g, 81%) was obtained from (Sp)-6
(0.070 g, 0.213 mmol) and ethanolamine (EA) (0.020 g, 0.019 mL,
0.320 mmol) after reflux for 18 h and crystallisation from hep-
20
and hexane. [a]D +7.9 (c 0.53, benzene); m.p. 140–142.58C;
tane. [a]D À86.5 (c 0.55, benzene); m.p. 151.5–1578C; H NMR
(600 MHz, [D6]DMSO,): d=2.1–2.79 (m, 1H, -CHHCH2-); 2.86–
2.93 (m, 1H, -CHHCH2-); 2.94–3.06 (m, 3H, -CH2CH2- and 23-
H); 3.06–3.18 (m, 3H, -CH2CH2-); 3.25–3.32 (m, 1H, 24-H);
1H NMR (400 MHz, [D6]DMSO, 258C): d=0.77 (d, JH,H
=
20
1
3
6.9 Hz, 3H, CH3); 0.80 (d, 3JH,H =6.9 Hz, 3H, CH3); 1.86–1.98
(m, 1H, 25-H); 2.52–2.62 (m, 1H, 23-H); 2.63–2.76 (m, 1H, 24-
H); 2.85–3.20 (m, 7H, -CH2CH2- and 24-H); 3.73–3.84 (m, 1H,
3
3.35–3.42 (m, 1H, 23-H); 3.40–3.47 (m, 1H, 24-H); 3.62–3.64 (m,
-CHHCH2-); 4.01–4.10 (m, 1H, -CHHCH2-); 6.49 (dd, JH,H
=
3
1H, -CHHCH2-); 4.04 (br.s, 1H, (C24)-OH); 6.49 (dd, JH,H
=
7.8 Hz, 4JH,H =1.8 Hz, 1H, 7H or 16-H); 6.57 (d, 4JH,H =1.8 Hz,
4
4
3
7.8 Hz, JH,H =1.8 Hz, 1H, 7-H); 6.55 (d, JH,H =1.8 Hz, 1H, 5-H);
1H, 5-H or 12-H); 6.62 (d, JH,H =7.8 Hz, 1H, 8-H or 15-H); 6.64
3
4
6.61 (d, JH,H =7.8 Hz, 1H, 8-H); 6.65 (d, JH,H =1.8 Hz, 1H, 15-
H); 6.73 (dd, JH,H =7.8 Hz, JH,H =1.8 Hz, 1H, 16-H); 6.79–6.85
(d, 4JH,H =1.8 Hz, 1H, 15-H or 8-H); 6.71 (dd, 3JH,H =7.8 Hz,
3
4
4
4JH,H =1.8 Hz, 1H, 16-H or 7-H); 6.75 (d, JH,H =1.8 Hz, 1H, 12-
(m, 1H, 20-H or 21-H); 6.85–6.90 (m, 1H, 21-H or 20-H); 6.92(
d, JH,H =1.8 Hz, 1H, 12-H); 7.08–7.12 (m, 1H, 22-H); 7.29–7.33
H or 5-H); 6.79–6.92 (m, 1H, 19-H and 20-H, or 22-H and 21-
H); 7.09–7.18 (m, 1H, 21-H or 20-H); 7.29–7.36 (m, 1H, 19-H or
22-H); 7.90 (s, 1H, CH=N); 9.17 (br. s, 1H, OH); MS (EI), m/z
(rel): 413 (32, M+), 412 (11), 382 (16), 311 (26), 219 (13), 218
4
(m, 1H, 19-H); 7.91 (s, 1H, CH=N); 9.13 (s, 1H, OH); MS
(EI), m/z (rel): 371 (18, M+), 196 (13, M+ÀCH2-
Isr. J. Chem. 2012, 52, 156 – 170
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.ijc.wiley-vch.de
167

Full Paper
R. P. Zhuravsky, V. I. Rozenberg et al.
(13), 217 (44, M+ÀCH2-C6H3(C6H5OH)-CH2), 216 (100), 196 (14,
CH2-C6H3(CH=NCH(iPr)CH2OH)-CH2), 195 (24), 182 (11), 181
(53), 178 (13), 165 (14), 152 (13), 144 (17), 143 (25), 132 (17), 131
(70), 130 (88), 129 (16), 128 (11), 115 (16). Anal. calcd for
C28H31NO2: C, 81.32; H, 7.56; N, 3.39. Found: C, 81.46; H, 7.69;
N, 3.31.
3JH,H =7.8 Hz, 4J=1.8 Hz, 1H, 16-H); 6.58–6.73 (m, 5H, PC-
arom-H); 6.78–6.84 (m, 1H, 22-H); 6.88–6.95 (m, 1H, 20-H);
7.06–7.13 (m, 1H, 21-H); 7.35–7.43 (m, 1H, 19-H); 7.86 (s, 1H,
CH=N); 9.15 (s, 1H, OH); MS (EI), m/z (rel): 427 (21, M+),
426 (15), 397 (28), 396 (100), 370 (19), 368 (19), 354 (29), 328
(15), 327 (10), 326 (24), 312 (14), 311 (60), 233 (12), 231 (18, M+
ÀCH2-C6H3(C6H5OH)-CH2), 230 (36), 209 (12), 197 (14), 196
(14, CH2-C6H3(CH=NCH(sBu)CH2OH)-CH2), 195 (48), 194
(15), 182 (16), 181 (70), 178 (19), 174 (27), 165 (13), 152 (15), 144
(19), 143 (35), 132 (13), 131 (35), 130 (57), 117 (12), 115 (14).
Anal. calcd for C29H33NO2: C, 81.46; H, 7.78; N, 3.28. Found: C,
81.44; H, 7.88; N, 3.04.
Aldimine (Rp,Sc)-29 (0.071 g, 94%) was obtained from (Rp)-7
(0.060 g, 0.183 mmol) and (S)-ValOH (0.028 g, 0.274 mmol) after
reflux for 12 h and crystallisation from 2:5 mixture of toluene/
20
hexane. [a]D +110.1 (c 0.63, benzene); m.p. 170–1728C;
1H NMR (400 MHz, [D6]DMSO, 258C): d=0.93 (d, JH,H
=
3
3
6.6 Hz, 3H, CH3); 1.04 (d, J=6.7 Hz, 3H, CH3); 1.94–2.08 (m,
1H, 25-H); 2.16–2.29 (m, 1H, -CHHCH2-); 2.69–2.97 (m, 3H,
-CH2CH2-); 3.07–3.29 (m, 3H, 23-H and -CH2CH2-); 3.60–3.71
(m, 1H, 24-H); 3.72–3.91 (m, 2H, -CHHCH2- and 24-H); 4.60–
4.70 (m, 1H, -CHHCH2-); 6.46–6.59 (m, 3H, PC-arom-H); 6.69
(br. s, 2H, PC-arom-H); 6.80–6.87 (m, 1H, 19-H or 22-H); 6.90–
7.00 (m, 1H, 20-H or 21-H); 7.10–7.24 (m, 2H, 21-H or 20-H and
PC-arom-H); 7.89–7.99 (m, 1H, 22-H or 19-H); 8.38 (s, 1H,
CH=N); 9.12 (s, 1H, OH); MS (EI), m/z (rel): 413 (96, M+),
412 (10), 396 (16, M+ÀH2O), 382 (28), 311 (57), 310 (57), 309
(15), 295 (18), 232 (29), 219 (33), 218 (100), 217 (87, M+ÀCH2-
C6H3(C6H5OH)-CH2), 216 (80), 196 (8, CH2-C6H3(CH=NCH-
(iPr)CH2OH)-CH2), 195 (24), 186 (33), 182 (12), 181 (49), 178
(12), 174 (17), 165 (13), 152 (15), 144 (15), 143 (17), 132 (19), 131
(52), 130 (69), 129 (18), 128 (11), 119 (11), 115 (12). Anal. calcd
for C28H31NO2: C, 81.32; H, 7.56; N, 3.39. Found: C, 81.51; H,
7.47; N, 3.35.
Aldimine (Sp,Sc)-30 (0.053 g, 62%) obtained from (Sp)-5 (0.066 g,
0.201 mmol) and (S)- LeuOH (0.035 g, 0.301 mmol) after reflux
i
for 17 h and crystallisation from a 4:1 mixture of toluene and
20
hexane. [a]D +16.7 (c 0.58, benzene); m.p. 118.5–1218C;
3
1H NMR (400 MHz, [D6]DMSO, 258C): d=1.05 (d, JH,H
=
6.7 Hz, 3H, CH3); 1.12 (d, 3JH,H =6.7 Hz, 3H, CH3); 1.99–2.14
(m, 1H, 25-H); 2.15–2.28 (m, 1H, 23-H); 2.62–2.82 (m, 2H,
-CHHCH2- and -CH2OH); 2.83–2.98 (m, 2H, 24-H and
-CHHCH2-); 3.06–3.16 (m, 1H, -CHHCH2-); 3.17–3.29 (m, 2H,
-CHHCH2- and 24-H); 3.43–3.56 (m, 1H, -CHHCH2-); 3.66–3.76
(m, 1H, -CHHCH2-); 3.77–3.91 (m, 1H, -CHHCH2-); 4.44–4.53
(m, 1H, -CHHCH2-); 6.32 (s, 1H, 5-H or 13-H); 6.52–6.63 (m,
2H, PC-arom.-H); 6.64–6.74 (m, 2H, PC-arom-H); 6.86 (d,
3JH,H =8.0 Hz, 1H, 22-H); 6.90–6.98 (m, 1H, 20-H); 7.12 (s, 1H,
13-H or 5-H); 7.13–7.22 (m, 1H, 21-H); 7.76 (d, 3JH,H =7.3 Hz,
1H, 19-H); 8.36 (s, 1H, CH=N); 9.14 (s, 1H, OH); MS (EI), m/
z (rel): 427 (24, M+), 397 (32), 396 (100), 370 (26), 326 (28), 312
(22), 311 (83), 231 (14, M+ÀCH2-C6H3(C6H5OH)-CH2), 230 (23),
196 (23, CH2-C6H3(CH=NCH-(sBu)CH2OH)-CH2), 195 (58), 194
(25), 181 (90), 174 (40), 167 (22), 149 (37), 144 (28), 143 (40), 131
(44), 130 (58). Anal. calcd for C29H33NO2: C, 81.46; H, 7.78; N,
3.28. Found: C, 81.44; H, 8.04; N, 3.79.
Aldimine (Sp,Sc)-29 (0.054 g, 71%) was obtained from (Sp)-7
(0.060 g, 0.183 mmol) and (S)-ValOH (0.028 g, 0.274 mmol) after
reflux for 16 h and crystallisation from a 2:5 mixture of toluene/
20
hexane. [a]D À136.1 (c 0.46, benzene); m.p. 186.5–1888C;
3
1H NMR (400 MHz, [D6]DMSO, 258C): d=1.05 (d, JH,H
=
6.7 Hz, 3H, CH3); 1.12 (d, 3JH,H =6.7 Hz, 3H, CH3); 1.99–2.14
(m, 1H, 25-H); 2.15–2.28 (m, 1H, 23-H); 2.62–2.82 (m, 2H,
-CHHCH2- and -CH2OH); 2.83–2.98 (m, 2H, 24-H and
-CHHCH2-); 3.06–3.16 (m, 1H, -CHHCH2-); 3.17–3.29 (m, 2H,
-CHHCH2- and 24-H); 3.43–3.56 (m, 1H, -CHHCH2-); 3.66–3.76
(m, 1H, -CHHCH2-); 3.77–3.91 (m, 1H, -CHHCH2-); 4.44–4.53
(m, 1H, -CHHCH2-); 6.32 (s, 1H, 5-H or 13-H); 6.52–6.63 (m,
2H, PC-arom-H); 6.64–6.74 (m, 2H, PC-arom-H); 6.86 (d,
3JH,H =8.0 Hz, 1H, 22-H); 6.90–6.98 (m, 1H, 20-H); 7.12 (s, 1H,
13-H or 5-H); 7.13–7.22 (m, 1H, 21-H); 7.76 (d, 3JH,H =7.3 Hz,
1H, 19-H); 8.36 (s, 1H, CH=N); 9.14 (s, 1H, OH); MS (EI), m/
z (rel): 413 (75, M+), 411 (10), 396 (15, M+ÀH2O), 382 (23), 311
(50), 310 (65), 309 (20), 295 (18), 293 (13), 232 (34), 219 (27), 218
(78), 217 (100, M+ÀCH2-C6H3(C6H5OH)-CH2), 216 (95), 215
(16), 214 (19), 213 (24), 196 (19, CH2-C6H3(CH=NCH-
(iPr)CH2OH)-CH2), 195 (47), 186 (43), 182 (20), 181 (76), 178
(16), 174 (21), 165 (27), 152 (29), 149 (44), 144 (26), 143 (32), 132
(28), 131 (57), 130 (83), 129 (25), 128 (17), 121 (15), 119 (15), 115
(21). Anal. calcd for C28H31NO2: C, 81.32; H, 7.56; N, 3.39.
Found: C, 81.57; H, 7.62; N, 3.28.
Aldimine (Sp,Sc)-31 (0.049 g, 22%) was obtained from (Sp)-7
(0.217 g, 0.661 mmol) and ethylenediamine (0.028 g, 0.031 mL,
0.462 mmol) after reflux for 34 h and repeated crystallization
from toluene/ethyl acetate. [a]D À72.2 (c 0.20, benzene); m.p.
20
222.5–2258C; 1H NMR (400 MHz, [D6]DMSO, 258C): d=2.17–
2.35 (m, 2H, -CH2CH2-); 2.68–2.99 (m, 8H, -CH2CH2-);3.08–3.29
(m, 4H, -CH2CH2-); 3.72–3.89 (m, 2H, -CH2CH2-); 4.07–4.23 (m,
2H,=N-CH2); 4.25–4.40 (m, 2H,=N-CH2); 6.37 (s, 2 H, 5-H or
13-H); 6.51–6.62 (m, 4H, PC-arom-H); 6.65–6.75 (m, 4H, PC-
arom-H); 6.81–6.93 (m, 4H, 20-H and 22-H); 7.08–7.18 (m, 2H,
21-H); 7.20 (s, 2 H, 13-H or 5-H); 7.71–7.81 (m, 2H, 19-H); 8.62
(s, 2H, CH=N); 9.15 (br. s, 2 H, OH); MS (EI), m/z (rel): 680
(34, M+), 679 (12), 663 (15, M+ÀOH), 483 (25, M+ÀCH2-
C6H3(C6H5OH)-CH2), 370 (14), 356 (11), 355 (23), 354 (22), 353
(14), 340 (17), 339 (10), 338 (18), 328 (16), 327 (16), 326 (35), 325
(13), 324 (17), 312 (19), 311 (76), 310 (90), 309 (41), 297 (12), 296
(11), 295 (36), 293 (17), 289 (10), 209 (15), 197 (15), 196 (19), 195
(56), 194 (20), 185 (19), 182 (20), 181 (100), 178 (19), 175 (20),
174 (20), 173 (22), 167 (16), 165 (25), 160 (31), 159 (25), 158 (91),
157 (18), 152 (24), 145 (18), 144 (80), 143 (42), 132 (19), 131 (40),
130 (79), 129 (22), 128 (22), 117 (22), 115 (22). Anal. calcd for
C48H44N2O2: C, 84.67; H, 6.51; N, 4.11. Found: C, 84.72; H, 6.66;
N, 4.58.
Aldimine (Rp,Sc)-30 (0.072 g, 92%) was obtained from (Rp)-6
(0.060 g, 0.183 mmol) and (S)-2-amino-3-methyl-1-penthanol
i
((S)- LeuOH) (0.032 g, 0.274 mmol) after reflux for 17 h and
20
crystallisation from 1:3 mixture of toluene/hexane. [a]D À51.4
(c 0.36, CHCl3); m.p. 189.5–191.58C; 1H NMR (400 MHz,
[D6]DMSO, 258C): d=0.60 (d, 3JH,H =6.0 Hz, 3H, 26-H); 0.74–
0.82 (m, 3H, 28-H); 0.83–0.94 (m, 2H, 25-H and 27-H); 1.17–
1.29 (m, 1H, 27-H); 2.50–2.58 (m, 1H, 23-H); 2.62–2.73 (m, 1H,
-CHHCH2-); 2.87–3.22 (m, 7H, -CH2CH2- and 24-H); 4.04–4.14
(m, 1H, -CHHCH2-); 4.20–4.27 (m, 1H, -CHHCH2-); 6.47 (dd,
Enantioselective diethylzinc addition to aldehydes catalyzed by
phenoxy-imines 16, 25–30
Typical experimental procedure: To a solution of aldimine 16,
25–30 (0.007 mmol) in toluene (0.28 mL), Et2Zn (0.142 mmol,
0.140 mL of 1 N solution in hexane) and aldehyde (benzaldehyde
168
www.ijc.wiley-vch.de
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Isr. J. Chem. 2012, 52, 156 – 170

Aryl[2.2]paracyclophane-Based Chiral Regioisomeric Analogs of Salicyl Aldehyde
or cyclohexanecarbaldehyde, 0.071 mmol) were successively
added by syringe at 08C. The resulting yellow solution was
warmed to room temperature and allowed to stir for an addition-
al 15 h period. The excess of Et2Zn was hydrolyzed with 1 N HCl
(0.25 mL); the reaction mixture was then diluted with Et2O
(4 mL), and H2O (3 mL). The organic layer was separated and
the aqueous fraction was additionally extracted with Et2O (5ꢁ
4 mL). The combined organic fractions were washed with brine
(2 mL) and dried with Na2SO4. After solvent removal the oily
residue without further purification was subjected to GC and
Chiral GC for conversion and enantiomeric excess analysis. The
conversion was determined by GC analysis (Hewlett–Packard
HP 5890 Series II gas chromatograph) on an HP-1 (12 mꢁ
0.25 mm) with N2 (15 psi) as carrier gas, split ratio 75:1. Inject
temperature 2008C, detector FID 2508C, temperature program:
408C (1 min), heat rate 308CminÀ1, end temperature 2508C
(10 min). Enantiomeric analysis of secondary alcohols was per-
formed by GC analysis (Sigma 2000 (PerkinElmer) on a Gamma
cyclodextrin Trifluoracetyl (G-TA) column (30 mꢁ0.25 mm) (1-
phenylpropanol) and on the Beta cyclodextrin Dimethyl B-DM
column (30 mꢁ0.25 mm) (1-cyclohexylpropanol) with He (15 psi)
as carrier gas, split ratio 75:1. Temperature data for 1-phenylpro-
panol: inject temperature 2208C, detector FID 2208C, column
temperature 1208C; the retention times (min) were 11.60 (S) and
12.20 (R). Temperature data for 1-cyclohexylpropanol: inject
temperature 2008C, detector FID 2208C, temperature program:
408C (1 min), heat rate 208CminÀ1, end temperature 1908C
(5 min); the retention times (min) were 18.70 (S) and 19.40 (R).
group in both structures were located in the Fourier density syn-
thesis while all other hydrogen atoms were calculated from the
geometrical point of view and refined with the riding model. All
calculations were performed with the SHELXTL software pack-
age.[31] Crystal data and structure refinement parameters are
listed in Table 2.
Crystallographic data for (Rp,Rc)-16 and (Rp,Sc)-25 have been de-
posited with the Cambridge Crystallographic Data Centre
(CCDC), deposition numbers 601914 and 601915, respectively.
Copies of the data can be obtained free of charge on application
to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44-
1223-335-033; e-mail: deposit @ccdc.cam.ac.uk.
Acknowledgements
Financial support for this work by the Russian Founda-
tion for Basic Research (Project No. 10–03–00898) is
gratefully acknowledged.
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X-ray crystallography: Single crystals were grown by slow evapo-
ration from MeOH solution. Diffraction data were collected on a
Syntex P21 diffractometer [l(MoKa)=0.71072 ꢀ, q/2q-scans] at
298 K for (Rp,Rc)-16 and on a Bruker SMART 1000 CCD diffrac-
tometer [l(MoKa)=0.71072 ꢀ, w-scans] at 120 K for (Rp,Sc)-25.
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full-matrix least-squares technique against F2 in the anisotropic-
isotropic approximation. The hydrogen atoms of the hydroxy
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Table 2. Crystal and structure refinement data for (Rp,Rc)-16 and
(Rp,Sc)-25.
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(Rp,Rc)-16
(Rp,Sc)-25
Formula
Mr
F(000)
T, K
Crystal system, Space group
Z(Z’)
a, ꢁ
b, ꢁ
C31H29NO
431.55
460
C31H29NO, CH4O
463.59
496
120
298
Monoclinic, P21 Monoclinic, P21/c
2(1)
2(1)
7.716(2)
10.122(3)
14.517(4)
90.283(7)
1133.9(6)
1.264
0.75
60
9839
5073
7.542(2)
17.129(6)
9.952(3)
102.68(2)
1254.3(6)
1.163, 3.33
0.75
52
2772
2523
1717
0.0560
0.1285
0.995
0.271, À0.224
c, ꢁ
b, 8
V, ꢁ3
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1, gcmÀ3
Chem. Soc. 2004, 126, 6314–6326.
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Gothelf, J. Org. Chem. 2004, 69, 2240–2250.
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Chem. Commun. 2002, 1038–1039; b) M. Mitani, R. Fur-
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Fujita, J. Am. Chem. Soc. 2002, 124, 7888–7889; c) Y. Tohi,
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2003, 36, 523–525; d) J. Saito, Y. Tohi, N. Matsukawa, M.
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m, cmÀ1
2Vmax,8
Reflections measured
Independent reflections
Observed reflections [I>2s(I)] 1872
R1
wR2
0.0643
0.1726
0.755
0.267, À0.191
GOF
D1max, D1min (eꢁÀ3
)
Isr. J. Chem. 2012, 52, 156 – 170
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.ijc.wiley-vch.de
169

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Received: August 18, 2011
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Published online: February 14, 2012
170
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Isr. J. Chem. 2012, 52, 156 – 170