Versatile switching in substrate topicity: Supramolecular chirality induction in di- and trinuclear host complexes

Article abstract of DOI:10.1002/chem.201200335

Supramolecular chirality effects have been achieved both for ditopic and monotopic substrates by using a programmable bis-salphen scaffold that incorporates either two or three Zn nuclei. The dinuclear host shows preferential chirogenesis in the presence

Full text of DOI:10.1002/chem.201200335

FULL PAPER
DOI: 10.1002/chem.201200335
Versatile Switching in Substrate Topicity: Supramolecular Chirality Induction
in Di- and Trinuclear Host Complexes
Martha V. Escꢀrcega-Bobadilla,[a] Giovanni Salassa,[a] Marta Martꢁnez Belmonte,[a]
Eduardo C. Escudero-Adꢀn,[a] and Arjan W. Kleij*[a, b]
Abstract: Supramolecular chirality ef-
fects have been achieved both for di-
topic and monotopic substrates by
using a programmable bis-salphen scaf-
fold that incorporates either two or
three Zn nuclei. The dinuclear host
shows preferential chirogenesis in the
presence of ditopic systems, whereas
effective chirality transfer to the trinu-
clear complex is realized through
monotopic binding. The mode of bind-
ing in the trinuclear host has been in-
vestigated through X-ray crystallogra-
phy, CD measurements, UV/Vis spec-
troscopy, and DFT analysis. The bis-sal-
phen scaffold holds promise for the de-
velopment of substrate-specific host
systems useful for determination of the
absolute configuration of various types
of organic molecules.
AHCTUNGTRENNUNG
Keywords: atropisomers · chirogen-
esis · monotopicity · Schiff bases ·
supramolecular chemistry
Introduction
binding in chirogenesis phenomena, chiral induction through
monotopic binding of a chiral guest remains extremely chal-
lenging.[9] Monotopic binding of suitable substrates is highly
attractive due to potential new applications, such as the de-
velopment of new chiral (supramolecular) ligands, and im-
proved protocols for the determination of absolute confor-
mations of a wide range of structurally different chiral sub-
strates. We report herein on an unusual trinuclear Schiff
base host complex in which the conformation is rigidified by
a central Zn ion; coordination of a series of suitable mono-
topic ligands to this central Zn ion results in effective chiral-
ity transfer to the host as supported by circular dichroism
(CD) spectroscopy. X-ray analysis, UV/Vis spectroscopy,
and density functional theory (DFT) calculations have fur-
ther been used to obtain more insight in the preferred bind-
ing of the guests to this host under these conditions.
Chirality represents an important phenomenon in chemical
sciences and in particular in the area of asymmetric synthe-
sis,[1] in which the production and analysis of chiral mole-
cules has been the subject of extensive and ongoing investi-
gation. Supramolecular chirality,[2] such as found in the
DNA double helix in biological systems[3] has been less stud-
ied but has the propensity to be exploited in many different
ways. Supramolecular chirogenesis,[4] that is, the induction of
chirality by means of a chiral substrate that locks a host
molecule into a preferred chiral state, is an emerging field
of science that has great potential for the determination of
absolute configurations of various substrates[5] and for use in
enantioselective catalysis[6] and material science.[7] In most
of these reported chirogenesis strategies, a nonchiral host
contains two binding sites that are useful for binding of di-
topic chiral guests. Upon binding of suitable guest mole-
cules, the structure of the host system is locked into one fa-
vored chiral conformation. In this context, Borovkov and
Inoue reported on ethane-bridged bisporphyrin systems that
show interesting chirogenesis effects in the presence of dis-
tinct ditopic chelators.[8] Despite the effectiveness of ditopic
Results and Discussion
Although bis-porphyrins have been widely studied as hosts
in supramolecular chirogenesis,[4,8] salphen-based hosts [sal-
phen=N,N’-1,2-phenylenebis-(salicylimine)] have recently
been reported as effective systems for binding of chiral car-
boxylates.[5a] Salphen systems have emerged as powerful
structures in supramolecular science and catalysis[10] due to
their huge potential as versatile building blocks. In a previ-
[a] Dr. M. V. Escꢀrcega-Bobadilla, G. Salassa,
Dr. M. Martꢁnez Belmonte, E. C. Escudero-Adꢀn,
Prof. Dr. A. W. Kleij
ous contribution[5a] we reported on a bis-Zn
ACHTNUTRGNE(NUG salphen) host
comprised of a biphenyl spacer in which the conformation
can be controlled upon binding of chiral acids. The bis-Zn-
Institute of Chemical Research of Catalonia (ICIQ)
Av. Paꢂsos Catalans 16, 43007 Tarragona (Spain)
Fax : (+34)977920828
E-mail: akleij@iciq.es
AHCTUNGTREG(NNNU salphen) host contained a built-in acetic acid guest that
[b] Prof. Dr. A. W. Kleij
needed to be exchanged for chiral carboxylates to induce
a chirogenesis effect. We realized that this built-in guest pro-
hibited the use of this supramolecular host system for other
types of more weakly binding ditopic guests and set out to
Catalan Institute for Research and Advanced Studies (ICREA)
Pg. Lluis Companys 23, 08010 Barcelona (Spain)
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201200335.
Chem. Eur. J. 2012, 00, 0 – 0
ꢃ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
1
&
ÞÞ
These are not the final page numbers!

explore the construction of carboxylate-free systems. This is
an important requisite for new host structures based on bis-
dimines,[11] and ligand 1 could be easily isolated in good
yield by a combination of monoketimine A with dialdehyde
B.[12] The isolation of 1 is a prerequisite for producing
a guest-free host; metalation of 1 by using ZnEt2 proceeds
Zn
to be strong (Ka =3.8ꢄ1010 mÀ1). This very high association
of acids to bis-Zn(salphen) hosts limited the use of the first-
ACHTUNGTRENNUNG(salphen) scaffolds because carboxylate binding proved
G
almost quantitatively and gives bis-ZnACTHUNGTERNNU(G salphen) 2 in 95%
generation host[5a] to exchange only with other, though
chiral, carboxylic acids with similar high binding affinities.
The replacement of the RCOOH unit by other potentially
ditopic substrate systems based on N,N-, N, O- or O,O-coor-
dination patterns was, therefore, not conceivable at relative-
ly low guest/host ratios. We therefore designed a new acid-
free host framework (i.e., 2 in Scheme 1) that is able to di-
rectly bind various ditopic guest molecules.
yield. Complex 2 contains an array of O-donor atoms that
may be useful for coordination to cations. We envisioned
that cation binding by these O-atoms would significantly
reduce its flexibility, and furthermore would lead to a struc-
ture with a central Lewis acidic binding site. Upon treat-
ment of 2 with an ethereal solution of ZnCl2, tri-Zn complex
3 (62%) was subsequently obtained; isolation of 3 from 2 is
greatly facilitated by simple and selective extraction of 2 by
using CH2Cl2 to give pure 3, or by filtration of the reaction
mixture. The difference between both multinuclear systems
is easily observed by 1H NMR spectroscopy ([D7]DMF);
whereas 2 is characterized by an imine resonance at d=
9.00 ppm, in 3 (d=9.29 ppm) this is located significantly
more downfield as a result of the presence of a third Lewis
acid center bound to the four O donors. Further confirma-
tion of the connectivity pattern in 2 and 3 was provided by
MALDI(+) mass spectrometry (see the Supporting Infor-
mation), and in the case of 3 by X-ray diffraction studies
(Figure 1). Complex 5 (prepared by using monoaldehyde C)
To construct these new types of bis-ZnACTHNUTRGNEUNG(salphen) hosts, we
took advantage of the higher stability of ketimines versus al-
and known ZnACTHNUGTRNEUNG(salphen) 6 were used as mononuclear refer-
ences for the spectroscopic studies.
The structure determined for 3[13] represents an unusual
trinuclear supramolecular system in which the two exterior
Zn metal centers are axially ligated by a chloride anion. The
Figure 1. X-ray molecular structure determined for 3 in the presence of
1,3,5-triaza-7-phosphaadamantane oxide. Ellipsoids were drawn at the
40% probability level. Cocrystallized solvent molecules and H atoms are
À
omitted for clarity. Selected bond lengths [ꢅ] and angles [8]: Zn1 N1=
À
À
À
2.1718(14), Zn1 N2=2.0570(15), Zn1 O(1)=1.9860(13), Zn1 O2=
À
À
À
2.1144(11), Zn1 Cl1=2.2204(5), Zn2 O1=1.9735(12), Zn2 O2=
À
À
À
2.0401(13), Zn2 O3=2.0082(11), Zn2 O4=2.0192(13), Zn2 O5=
2.0209(13); N2-Zn1-N1=77.92(6), O1-Zn1-O2=77.99(5), O1-Zn1-N2=
125.15(6), O2-Zn1-N1=142.92(5), O2-Zn1-Cl1=109.64(4), N1-Zn1-Cl1=
107.42(4), O2-Zn2-O4=169.835, O3-Zn2-O1=139.11(5), O1-Zn2-O4=
97.16(6), O1-Zn2-O5=110.09(5), O4-Zn2-O5=97.45(5).
Scheme 1. Synthesis of 2–3 via precursor bis-ligand 1; also shown are the
mononuclear compounds 5 and 6 used as controls in this study.
&
2
&
www.chemeurj.org
ꢃ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 0000, 00, 0 – 0
ÝÝ
These are not the final page numbers!

Di- and Trinuclear Host Complexes
FULL PAPER
Table 1. UV/CD response after chiral guest addition.[a]
charge of these two anions is balanced by a third Zn cation
[Zn2] that is located in the interior of the structure and is
Host/Guest
Guest structure
lmax
De
[mÀ1 cmÀ1
]
[nm]
ligACHTUNGTRENNUNGated by four O atoms of the bis-salphen scaffold that
reside in an approximately planar arrangement around Zn2.
The coordination geometry around Zn2 is completed by the
presence of an axially interacting phosphine oxide that was
present during the crystallization process. The presence of
the latter demonstrates that suitable monotopic, chiral lig-
2/quinidine
3/quinidine
438
444
À2.5
À4.6
2/cinchonidine
3/cinchonidine
408
410
À2.5
À4.8
ACHTUNGTRENNUNGands may be able to induce a preferred conformation of the
biphenyl backbone in Zn3 structure 3 resulting in an excess
of one of the two atropisomers having either P or M helical
conformations. This is an additional and important advant-
age over the first-generation host,[5a] amplifying the applica-
tion potential to a wide range of ditopic and monotopic sub-
strates.
2/cinchonine
3/cinchonine
410
428
3.6
4.9
Both multinuclear Schiff base complexes 2 and 3 were
then combined with a number of potentially ditopic and
monotopic chiral substrates (O and N donors) to examine
the chiral induction effects (Table 1, Figure 2, and the Sup-
porting Information). Typical ditopic systems, such as di-
2/(À)-nicotine
3/(À)-nicotine
0
432
0
2.4
2/(R)-dimethylamino pyrroli-
dine
0
0
ACHTUNGTRENNUNGamines and diols, produced a clear CD response in the pres-
3/(R)-dimethylamino pyrroli-
dine
2/(S)-binol
3/(S)-binol
462
3.6
ence of Zn2 complex 2, whereas in most cases these same
substrates caused only a slight CD response or no response
at all in the presence of trinuclear 3. Interestingly, when sub-
strates with typical monotopic binding modes to Lewis acid
metals were combined with 3, significantly higher CD re-
sponses were noted compared with 2. A selection of (cin-
chona) alkaloids and a chiral pyrrolidine gave fairly similar
results (i.e., a comparable increase in the molar ellipticity)
and showed principally CD responses in the presence of 3.
As expected, mononuclear complexes 5 and 6 showed no
CD responses for various substrates, including cinchonidine,
quinidine, (À)-nicotine and (R)-dimethylamino pyrrolidine,
which demonstrates the need for the bis-salphen scaffold in
the generation of chirogenesis effects.
430
0
4.4
0
2/(S)-binaphthyldiamine
3/(S)-binaphthyldiamine
458
0
31.7
0
2/
mine
3/(R,R)-diphenyl ethylenedia-
mine
ACHTUNGTNER(NUNG R,R)-diphenyl ethylenedia-
468
470
46.4
10.5
AHCTUNGTRENNUNG
2/
3/
U
434
0
1.3
0
The alkaloids are comprised of an N-heterocyclic frag-
ment that is able to axially coordinate to the central Zn
ion,[14] whereas the tertiary amines in these structures have
been reported to only bind very weakly.[15] The fact that no
observable changes were noted in the CD spectra recorded
for (À)-nicotine and (R)-dimethylamino pyrrolidine with
Zn2 complex 2 is further testament to the negligible coordi-
nation of the tertiary amine functions (see the Supporting
Information). For the cinchona alkaloid structures, it seems
plausible to suggest some degree of ditopic binding in the
presence of 2 involving a N,O-coordination pattern. The
binding of cinchonidine to 3 was then further investigated
by UV/Vis spectroscopy and fitting of the titration data to
a 1:1 binding model gave an association constant Ka of 3.3ꢄ
104 mÀ1. The presence of a clear isosbestic point in the UV/
Vis spectra indicates that multiple binding of cinchonidine
guests under these conditions is not favored (see the Sup-
porting Information) and exemplifies the preferred binding
of monotopic systems to the central Zn ion in 3 under these
conditions.
2/(R)-phenylglycinol
3/(R)-phenylglycinol
422
422
4.9
2.5
2/(À)-amineindanol
3/(À)-amineindanol
446
450
25.8
2.4
2/(+)-amineindanol
3/(+)-amineindanol
448
458
À22.4
2.3
[a] Measured at RT after addition of 20 equivalents of chiral guest to the
corresponding host (2ꢄ10À5 m) freshly prepared in CH2Cl2.
lish the preferred conformation of the host upon binding of
(À)-cinchonidine. For both diastereoisomers (M)-(À) and
(P)-(À), the UV/Vis and CD traces were calculated and
compared with the observed data (Figure 3). The computa-
tional data for the (M)-(À) diastereoisomer is in good agree-
ment with the experimental data, showing a first (larger)
negative Cotton effect followed by a smaller second positive
Cotton effect. The electronic transitions responsible for
these effects have host-based p–p* character, as supported
by frontier orbital analysis (see the Supporting Information).
DFT analysis (see the Supporting Information) of the 1:1
host–guest complex 3·cinchonidine was performed to estab-
Chem. Eur. J. 2012, 00, 0 – 0
ꢃ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
&
3
&
ÞÞ
These are not the final page numbers!

A. W. Kleij et al.
Figure 2. CD spectra of trinuclear complex 3 combined with 20 equivalents of cinchonine (red trace) or cinchonidine (green trace) in CH2Cl2 at RT. Blue
trace: complex 3 without additive.
Figure 3. Computed UV/CD traces for a) the M conformation and b) P conformation of 3 for the host–guest complex 3·cinchonidine. c) observed UV/
CD spectrum.
The CD data also imply that 3 will preferentially adopt the
(P)-(+)-conformation in the presence of (+)-cinchonine as
substrate (cf. Figure 2).
&
4
&
www.chemeurj.org
ꢃ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 0000, 00, 0 – 0
ÝÝ
These are not the final page numbers!

Di- and Trinuclear Host Complexes
FULL PAPER
elemental analysis calcd (%) for C52H34N4O4Zn2·2H2O: C 66.05, H 4.05,
N 5.92; found: C 66.03, H 3.53, N 5.78.
Conclusion
Bis-salphen-Zn3 (3): ZnCl2 (0.055 mL, 1m in ethyl ether, 0.055 mmol) was
added to a solution of 2 (50 mg, 0.055 mmol) in anhydrous THF (10 mL).
The reaction was stirred at RT for 18 h, then the yellow precipitate was
filtered off and dried (yield: 36 mg, 62%). 1H NMR (300 MHz,
We present herein a new bimetallic salphen scaffold that
can be simply rigidified by using a metal cation. The pres-
ence of this cation creates a new host system 3 that allows
for monotopic binding of chiral substrates, whereas parent
complex 2 is especially suited for ditopic binding of various
chiral guest molecules. In both cases, supramolecular chirali-
ty effects have been observed through CD measurements
and the conformational isomerism was further analyzed by
DFT. Complex 2 has great potential as a programmable and
modular host system (unlike the first-generation host)[5a] for
the binding of a large variety of substrates through either di-
topic or monotopic (cf. 3, after divalent cation addition) co-
ordination patterns and thus the development of effective
systems for measuring absolute configurations of chiral mol-
ecules.
[D7]DMF): d=6.13 (brs, 4H; ArH), 6.92 (m, 4H; ArH), 7.09 (t, JHH
6.1 Hz, 6H; ArH), 7.31 (m, 4H; ArH), 7.47 (t, JHH =7.3 Hz, 2H; ArH),
7.58 (m, 8H; ArH), 7.78 (d, JHH =7.7 Hz, 2H; ArH), 7.87 (d, JHH
=
=
8.1 Hz, 2H; ArH), 9.29 ppm (s, 2H; CHald); 13C{1H} NMR (125 MHz,
[D7]DMF): d=116.07, 116.15, 118.06, 122.16, 122.91, 124.28, 125.33,
126.98, 127.47, 127.84, 128.56, 128.57, 130.84, 131.73, 135.00, 137.00,
137.56, 138.61, 140.34, 141.32, 166.19, 166.88, 174.05 pp,; MS (MALDI+):
m/z calcd for C52H34ClN4O4Zn3: 1007.0; found: 1007.1 [MÀCl]+; elemen-
tal analysis calcd (%) for C52H34Cl2N4O4Zn3·2H2O·5CH2Cl2: C 45.44, H
3.21, N 3.72; found: C 45.69, H 2.20, N 4.05.
Ketimine (4): (E)-2-(((2-aminophenyl)imino)ACTHNUGRTNEUNG(phenyl)methyl) phenol
(527 mg, 1.83 mmol) and 2-hydroxy-[1,1’-biphenyl]-3-carbaldehyde
(362 mg, 1.83 mmol) were dissolved in (MeOH 10 mL) and stirred for
48 h. A yellow suspension was formed, and the yellow solid was filtered
and washed with methanol (yield: 823 mg, 96%). 1H NMR (300 MHz,
CDCl3): d=6.74 (t, JHH =7.6 Hz, 1H; ArH), 6.81–6.85 (m, 1H; ArH),
6.98–7.43 (m, 16H; ArH), 7.47 (m, 1H; ArH), 7.56 (d, JHH =6.9 Hz, 2H;
ArH), 8.45 (s, 1H; CHald), 13.60 (s, 1H; OH), 14.07 ppm (s, 1H; OH);
13C{1H} NMR (100 MHz, CDCl3): d=117.92, 118.05, 118.92, 118.98,
119.54, 119.62, 123.18, 125.48, 126.87, 127.05, 127.87, 128.03, 128.50,
128.96, 129.32, 129.82, 131.67, 132.39, 133.40, 134.18, 134.59, 137.40,
139.94, 141.60, 158.65, 162.70, 163.13, 163.15, 174.74 ppm; HRMS (ESIÀ,
MeOH): m/z calcd for C32H23N2O2: 467.1760; found: 467.1772 [MÀH]À.
Experimental Section
General methods: All starting materials were purchased from commer-
cial sources and used without further purification. Compounds (E)-2-
(((2-aminophenyl)imino)
2,2ꢆ-dihydroxy-1,1’-biphenyl (B),[12b] 2-hydroxy-[1,1’-biphenyl]-3-carbalde-
hyde (C)[16] and Zn(salphen) complex 6[17] were prepared by using a previ-
(phenyl)methyl)phenol (A)[12a] 3,3’-diformyl-
ACHTUNGTRENNUNG
Zn
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
and Zn
AHCTUNGTRENNUNG
ously reported methodology. Elemental analyses were performed at the
Unidad de Anꢀlisis Elemental of the University of Santiago de Compos-
tela (Spain). All NMR measurements were carried out by using
a Bruker-400 MHz spectrometer at ambient temperature unless stated
otherwise, and chemicals shifts are given in parts per million versus TMS.
Mass spectrometric data were obtained from the Research Support unit
of the ICIQ, and MALDI-TOF experiments were carried out with
pyrene as matrix. UV/Vis spectra were recorded by using a Shimadzu
UV1800 Spectrophotometer. CD spectra were measured on a Chirascan
instrument from Applied Photophysics.
bined and stirred for 18 h. Then the solvent was evaporated and the
yellow residue triturated with MeOH to give the title compound as
a
yellow crystalline solid (yield: 97 mg, 87%). 1H NMR (400 MHz,
[D6]DMSO): d=6.27 (t, JHH =8.1 Hz, 1H; ArH), 6.49 (d, 3JHH =8.1 Hz,
4JHH =1.1 Hz, 1H; ArH), 6.60 (t, JHH =7.5 Hz, 1H; ArH), 6.72 (d, JHH
=
3
8.5 Hz, 4JHH =1.1 Hz, 1H; ArH), 6.83 (m, 1H; ArH), 6.87 (d, JHH
=
3
8.3 Hz, 4JHH =1.8 Hz, 1H; ArH), 7.09 (m, 2H; ArH), 7.22–7.30 (m, 3H;
ArH), 7.38–7.42 (m, 7H; ArH), 7.57 (d, JHH =7.1 Hz 1H; ArH), 7.77 (d,
3JHH =8.1 Hz, 4JHH =1.1 Hz, 2H; ArH), 8.90 ppm (s, 1H, CHald);
13C{1H} NMR (100 MHz, [D6]DMSO): d=112.22, 122.98, 117.05, 120.13,
120.52, 123.20, 124.25, 125.54, 125.83, 125.93, 127.53, 128.24, 128.45,
128.66, 129.24, 133.04, 133.26, 134.31, 134.58, 135.91, 136.84, 139.61,
140.01, 140.08, 163.01, 169.81, 172.33, 173.49 ppm; MS (MALDI+): m/z
calcd for C32H22N2O2Zn: 530.1; found: 530.2 [M+]; elemental analysis
calcd (%) for C32H22N2O2Zn: C 72.26, H 4.17, N 5.27; found: C 71.88, H
4.51, N 5.27.
Diketimine (1): (E)-2-(((2-aminophenyl)imino)ACTHNUGRTNEUNG(phenyl)methyl) phenol
(500 mg, 1.75 mmol) and 3,3’-diformyl-2,2ꢆ-dihydroxy-1,1ꢆ- biphenyl
(210 mg, 0.88 mmol) were dissolved in MeOH (10 mL) and the solution
was heated at reflux for 24 h. The precipitate formed was then filtered to
1
give the title compound as a yellow solid (yield: 461 mg, 67%). H NMR
(500 MHz, CDCl3): d=6.66 (t, JHH =7.1 Hz, 2H; ArH), 6.82 (m, 2H;
ArH), 6.90 (t, JHH =7.6 Hz, 2H; ArH), 7.06 (m, 10H; ArH), 7.17 (t,
CD measurements with different chiral guests: A solution of the corre-
sponding chiral guest (2ꢄ10À3 m) in CH2Cl2 (400 mL) was added to a solu-
tion of either 2, 3, 5, or 6 (2ꢄ10À5 m) in CH2Cl2 (2 mL) in a 1 cm quartz
cuvette with a microliter syringe. CD and UV/Vis spectra were recorded
simultaneously by using freshly prepared analyte solutions.
J
HH =7.5 Hz, 4H; ArH), 7.23 (m, 10H; ArH), 7.45 (d, JHH =7.5 Hz,
4JHH =1.4 Hz, 2H; ArH), 8.32 (s, 2H; CHald), 13.21 (s, 2H; OH),
14.07 ppm (s, 2H; OH); 13C{1H} NMR (125.5 MHz, CDCl3): d=117.94,
118.10, 118.51, 119.59, 119.62, 119.72, 123.36, 125.63, 126.77, 127.98,
128.74, 129.01, 131.96, 132.52, 133.37, 134.69, 135.84, 140.54, 141.40,
158.84, 162.82, 163.66, 174.77 ppm; HRMS (MALDI+): m/z calcd for
C52H39N4O4: 783.2971; found: 783.2982 [M+H]+.
Calculation of the association constant of 3 with cinchonidine: The UV/
Vis titration data obtained by using 3 (see the Supporting Information)
were analyzed by using SPECFIT/32 considering two colored species
(free 3 and 3ꢀ(À)-cinchonidine) with two components (3 and (À)-cincho-
nidine). The concentration of 3 (2ꢄ10À5 m) was held constant and the
concentration of (À)-cinchonidine was varied. The absorption spectrum
of free 3 was imported into SPECFIT/32. The association constant of 3
Bis-ZnACHTUNGTRENNUNG(salphen) (2): ZnEt2 (0.51 mL, 1m in hexanes, 0.51 mmol) was
slowly added to a solution of 1 (200 mg, 0.255 mmol) in anhydrous THF
(20 mL). The reaction was stirred at RT for 18 h, then the orange precipi-
tate was filtered and dried (yield: 220 mg, 95%). 1H NMR (400 MHz,
[D7]DMF): d=6.33 (t, JHH =7.5 Hz, 2H; ArH), 6.54 (d, JHH =7.4 Hz, 2H;
ArH), 6.58 (d, JHH =8.9 Hz, 2H; ArH), 6.75 (d, JHH =8.4 Hz, 2H; ArH),
6.86 (t, JHH =7.8 Hz, 2H; ArH), 6.93 (d, JHH =8.2 Hz, 2H; ArH), 7.07 (t,
with (À)-cinchonidine was determined to be Ka =3.3ꢄ10À4 mÀ1
.
DFT calculations: All calculations were performed by using the Gaussi-
an 09 (G09) program package[18] employing the DFT method with the
CAM-B3LYP functional.[19] The LanL2DZ basis set[20] and effective core
potential were used for the Zn and Cl atoms, and the split-valence 6-
31G** basis set[21] was applied for all other atoms. Geometry optimiza-
tions of complex 3 were performed without any constraint and the nature
of all stationary points was confirmed by normal-mode analysis. Thirty
singlet excited states were determined starting from optimized geometry
J
HH =7.7 Hz, 2H; ArH), 7.18 (t, JHH =7.7 Hz, 2H; ArH), 7.33 (m, 8H;
ArH), 7.41 (d, JHH =7.2 Hz, 2H; ArH), 7.47 (m, 8H; ArH), 7.77 (d,
HH =8.0 Hz, 2H; ArH), 9.05 ppm (s, 2H; CHald); 13C{1H} NMR
J
(125 MHz, [D7]DMF, 298 K): d=113.42, 117.78, 121.25, 122.32, 124.52,
125.22, 126.20, 127.01, 129.41, 129.62, 130.14, 134.11, 135.54, 135.76,
137.89, 138.75, 140.99, 141.89, 163.34, 164.17, 172.43, 173.94, 174.86 ppm;
MS (MALDI+): m/z calcd for C52H34N4O4Zn2: 908.1; found: 908.1 [M]+;
Chem. Eur. J. 2012, 00, 0 – 0
ꢃ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
&
5
&
ÞÞ
These are not the final page numbers!

A. W. Kleij et al.
by using non-equilibrium TDDFT[22] calculations. Simulations of the elec-
tronic spectrum and the CD spectrum were obtained using GaussSum
2.2.5 package.[23]
[9] a) J. M. Lintuluoto, V. V. Borovkov, Y. Inoue, J. Am. Chem. Soc.
2002, 124, 13676–13677; b) V. V. Borovkov, J. M. Lintuluoto, Y.
Inoue, J. Am. Chem. Soc. 2001, 123, 2979–2989.
[10] a) C. W. Whiteoak, G. Salassa, A. W. Kleij, Chem. Soc. Rev. 2012,
41, 622–631; b) S. J. Wezenberg, A. W. Kleij, Angew. Chem. 2008,
120, 2388; Angew. Chem. Int. Ed. 2008, 47, 2354; c) J. K.-H. Hui, Z.
Yu, M. J. MacLachlan, Angew. Chem. 2007, 119, 8126; Angew.
Chem. Int. Ed. 2007, 46, 7980.
[11] a) P. D. Frischmann, J. J. Jiang, J. K.-H. Hui, J. J. Grzybowski, M. J.
MacLachlan, Org. Lett. 2008, 10, 1255–1258; b) T. Glaser, Chem.
Commun. 2011, 47, 116–130.
X-ray diffraction studies: The measured crystals were stable under at-
mospheric conditions; however, they were treated under inert conditions
and immersed in perfluoropolyether as a protecting oil for manipulation.
Data Collection: Measurements were made by using a Bruker–Nonius
diffractometer equipped with an APPEX 2 4 K CCD area detector,
a FR591 rotating anode with MoKa radiation, Montel mirrors, and a Kryo-
flex low-temperature device (T=À1738C). Full-sphere data collection
was used with w and f scans. Apex2 v. 2011.3 (Bruker–Nonius 2008) was
used for data collection, Saint+ version 7.60A (Bruker AXS 2008) was
used for data reduction, and SADABS v. 2008-1 (2008) was used for ab-
sorption correction. Structure solution was performed by using
SHELXTL version 6.10 (Sheldrick, 2000).[24] Structure Refinement:
SHELXTL-97-UNIX VERSION.
[12] For the synthesis of A see: a) A. Kꢇmpfe, E. Krote, J. Wagner, Eur.
J. Inorg. Chem. 2009, 1027–1035; For B: b) H.-C. Zhang, W.-S.
Huang, L. Pu, J. Org. Chem. 2001, 66, 481.
[13] Crystallographic
data
for
3·C6H12N3PO:
Formula
C61H52Cl8N7O5P1Zn3; Mr =1473.84; crystal size 0.20ꢄ0.10ꢄ
0.05 mm3; triclinic; space group P1; a=12.5137(3) ꢅ, b=
¯
14.0186(4) ꢅ, c=19.9889(6) ꢅ; a=94.5050(10)8, b=105.8490(10)8,
g=114.2540(10)8; V=3001.89(14)8; Z=1; 1calcd =1.630 mgMÀ3; m-
ACHUTNGRENNUG CAHTUNGTREN(NGUN min/max)=1.08/37.30; 25607
(MoKa)=1.629 mmÀ1; T=100(2) K; q
Acknowledgements
reflections collected; 20881 unique reflections (Rint =0.0274); ab-
sorption correction empirical; refinement method: full-matrix least-
squares on F2 ; data/restraints/parameters: 20881/42/793; GOF on
F2 =1.019; R1 =0.0415 and wR2 =0.0975 [I>2s(I) ]; R1 =0.0661 and
wR2 =0.1086 (all data); largest diff. peak and hole: 1.104 and À0.845
e3 ꢅÀ3 CCDC-853355 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge from
This work was supported by ICIQ, ICREA, and the Spanish Ministry of
Economics and Competitiveness (MINECO, project CTQ2011-27385).
We thank Dr. Noemꢁ Cabello and Sofia Arnal for the mass spectrometric
studies.
The
Cambridge
Crystallographic
Data
Centre
via
[1] a) Asymmetric Synthesis—The Essentials, 2nd ed. (Eds.: M. Christ-
man, S. Brꢇse), Wiley-VCH, Weinheim, 2008; b) T. P. Yoon, E. N.
Jacobsen, Science 2003, 299, 1691–1693; c) Asymmetric Catalysis on
Industrial Scale (Eds.: H.-U. Blaser, S. Schmidt), Wiley-VCH, Wein-
heim 2004.
[2] a) M. Suꢀrez, N. Branda, J.-M. Lehn, A. Decian, J. Fischer, Helv.
Chim. Acta 1998, 81, 1–13; b) B. L. Feringa, R. A. van Delden, N.
Koumura, E. M. Geertesema, Chem. Rev. 2000, 100, 1789–1816;
c) L. J. Prins, F. de Jong, P. Timmerman, D. N. Reinhoudt, Nature
2000, 408, 181–184; d) Supramolecular Chirality (Topics in Current
Chemistry, Vol. 265) (Eds.: M. Crego-Calama, D. N. Reinhoudt),
Springer, Berlin 2006; e) D. B. Amabilino, Chirality at the Nano-
scale: Nanoparticles, Surfaces, Materials and More, Wiley-VCH,
Weinheim 2009; f) T. F. A. de Greef, M. M. J. Smulders, M. Wolffs,
A. P. H. J. Schenning, R. P. Sijbesma, E. W. Meijer, Chem. Rev. 2009,
109, 5687; g) N. Berova, G. Pescitelli, A. G. Petrovic, G. Proni,
Chem. Commun. 2009, 5958.
[3] Biochemistry, 2nd ed. (Eds.: D. Voet, J. G. Voet), Wiley, New York
1995.
[4] a) G. A. Hembury, V. V. Borovkov, Y. Inoue, Chem. Rev. 2008, 108,
1–73; b) V. V. Borovkov, Y. Inoue, Top. Curr. Chem. 2006, 265, 89–
146; c) V. V. Borovkov, G. A. Hembury, Y. Inoue, Acc. Chem. Res.
2004, 37, 449–459.
[5] a) S. J. Wezenberg, G. Salassa, E. C. Escudero-Adꢀn, J. Benet-Buch-
holz, A. W. Kleij, Angew. Chem. 2011, 123, 739–742; Angew. Chem.
Int. Ed. 2011, 50, 713–716; b) J. Etxebarria, A. Vidal-Ferran, P. Bal-
lester, Chem. Commun. 2008, 5939–5940; c) G. Proni, G. Pescitelli,
X. Huang, K. Nakanishi, N. Berova, J. Am. Chem. Soc. 2003, 125,
12914.
[6] For very recent work, see: a) P. Dydio, C. Rubay, T. Gadzikwa, M.
Lutz, J. N. H. Reek, J. Am. Chem. Soc. 2011, 133, 17176–17179;
b) P. W. N. M. van Leeuwen, D. Rivillo, M. Raynal, Z. Freixa, J. Am.
Chem. Soc. 2011, 133, 18562–18565.
www.ccdc.cam.ac.uk/data_request/cif.
[14] a) S. J. Wezenberg, E. C. Escudero-Adꢀn, J. Benet-Buchholz, A. W.
Kleij, Org. Lett. 2008, 10, 3311–3314; b) E. C. Escudero-Adꢀn, J.
Benet-Buchholz, A. W. Kleij, Eur. J. Inorg. Chem. 2009, 3562–3568.
[15] A. Dalla Cort, L. Mandolini, C. Pasquini, K. Rissanen, L. Russo, L.
Schiaffino, New J. Chem. 2007, 31, 1633–1638.
[16] C. Gçrl, H. G. Alt, J. Organomet. Chem. 2007, 692, 5727.
[17] a) A. W. Kleij, D. M. Tooke, A. L. Spek, J. N. H. Reek, Eur. J. Inorg.
Chem. 2005, 4626; b) A. W. Kleij, D. M. Tooke, M. Kuil, M. Lutz,
A. L. Spek, J. N. H. Reek, Chem. Eur. J. 2005, 11, 4743.
[18] Gaussian 09, Revision 7.0, M. J. Frisch, G. W. Trucks, H. B. Schlegel,
G. E. Scuseria, M. A. Robb, J. R. Cheeseman, G. Scalmani, V.
Barone, B. Mennucci, G. A. Petersson, H. Nakatsuji, M. Caricato, X.
Li, H. P. Hratchian, A. F. Izmaylov, J. Bloino, G. Zheng, J. L. Son-
nenberg, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa,
M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, T. Vreven,
J. A. Montgomery, Jr., J. E. Peralta, F. Ogliaro, M. Bearpark, J. J.
Heyd, E. Brothers, K. N. Kudin, V. N. Staroverov, R. Kobayashi, J.
Normand, K. Raghavachari, A. Rendell, J. C. Burant, S. S. Iyengar,
J. Tomasi, M. Cossi, N. Rega, J. M. Millam, M. Klene, J. E. Knox,
J. B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R. E.
Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W.
Ochterski, R. L. Martin, K. Morokuma, V. G. Zakrzewski, G. A.
Voth, P. Salvador, J. J. Dannenberg, S. Dapprich, A. D. Daniels, ꢈ.
Farkas, J. B. Foresman, J. V. Ortiz, J. Cioslowski, D. J. Fox, Gaussian,
Inc., Wallingford CT, 2009.
[19] T. Yanai, D. Tew, N. Handy, Chem. Phys. Lett. 2004, 393, 51.
[20] P. J. Hay, W. R. Wadt, J. Chem. Phys. 1985, 82, 270.
[21] A. D. McLean, G. S. Chandler, J. Chem. Phys. 1980, 72, 5639.
[22] a) M. E. Casida, C. Jamorski, K. C. Casida and D. R. Salahub, J.
Chem. Phys. 1998, 108, 4439; b) R. E. Stratmann, G. E. Scuseria,
M. J. Frisch, J. Chem. Phys. 1998, 109, 8218.
[23] N. M. OꢆBoyle, A. L. Tenderholt, K. M. Langner, J. Comput. Chem.
2008, 29, 839.
[24] SHELXTL Crystallographic System Version 5.10, G. M. Sheldrick,
Bruker AXS, Inc. Madison (Wisconsin, USA) 1998.
[7] a) V. V. Borovkov, T. Harada, G. A. Hembury, Y. Inoue, R. Kuroda,
Angew. Chem. 2003, 115, 1788–1791; Angew. Chem. Int. Ed. 2003,
42, 1746–1749; b) L. Valli, S. Casilli, L. Giotta, B. Pignataro, S.
Conoci, V. V. Borovkov, Y. Inoue, S. Sortino, J. Phys. Chem. B 2006,
110, 4691–4698.
Received: January 31, 2012
[8] For a review, see: V. Borovkov, Symmetry 2010, 2, 184–200.
Published online: && &&, 0000
&
6
&
www.chemeurj.org
ꢃ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 0000, 00, 0 – 0
ÝÝ
These are not the final page numbers!

Di- and Trinuclear Host Complexes
FULL PAPER
Host with the most! Supramolecular
hosts based on bis-ZnACTHNUGTRNEUNG(salphen) scaf-
Supramolecular Chirality
folds have been prepared that allow
for either monotopic or ditopic binding
of suitable chiral guest molecules; this
binding results in chirogenesis effects
that can be programmed through rigid-
ification of the host by simple cation
addition. This new host has potential
for the determination of the absolute
configurations of various chiral sub-
strates through either di- or monotopic
binding modes.
M. V. Escꢀrcega-Bobadilla, G. Salassa,
M. Martꢁnez Belmonte,
E. C. Escudero-Adꢀn,
A. W. Kleij* ................... &&&& — &&&&
Versatile Switching in Substrate
Topicity: Supramolecular Chirality
Induction in Di- and Trinuclear Host
Complexes
Chem. Eur. J. 2012, 00, 0 – 0
ꢃ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
&
7
&
ÞÞ
These are not the final page numbers!