Towards modular design of chiroptically switchable molecules based on formation and cleavage of metal-ligand coordination bonds

Article abstract of DOI:10.1055/s-0029-1217090

The results presented in this paper demonstrate that the proposed design of C₂-symmetric, pentadentate achiral or chiral ligands 8a-d and 15 allows to generate, upon coordination with Ni(II) and Pd(II), the corresponding diastereomeric complexes possessing three new elements of chirality: stereogenic axis, center, and helix. Of particular importance is that due to the specific steric characteristics of the designed ligands the formation of the corresponding diastereomeric products is highly stereoselective allowing preparation of only two out of four possible stereochemical combinations. For instance, each diastereoisomeric product (R_a,P_h ,S_c)-9a and (R_a,M_h,R_c)-12a can be selectively prepared and characterized in solid state, simply by the choice of the chelating metal [Ni(II) or Pd(II)]. Furthermore, introduction of stereochemical information into the ligands design with application of a simple chiral Amine Module allows for complete transfer of the corresponding stereochemistry to the newly generated axial, helical, and central chirality. For example, starting with chiral ligand (R)-15, out of eight possible products, only a single product of (R_c,R_a,P_h ,S_c) absolute configuration was obtained in the solid state. Taking into account the modular nature of this design, one may agree that modification of the three major phenone, acid, and amine modules, or application of different metals, will allow for virtually unlimited structural and functional flexibility in fine-tuning the diastereomeric relationships of this type of complexes making them more selective and controllable by an external stimulus.

Full text of DOI:10.1055/s-0029-1217090

PAPER
49
Towards Modular Design of Chiroptically Switchable Molecules Based on
Formation and Cleavage of Metal–Ligand Coordination Bonds
Modular
D
esign of
a
Chiroptica
d
lly Switchab
i
le
M
ol
m
ecules A. Soloshonok,* Hisanori Ueki
Department of Chemistry and Biochemistry, University of Oklahoma, Norman, OK 73019, USA
Fax +1(405)3256111; E-mail: vadim@ou.edu
Received 10 July 2009; revised 22 August 2009
and switchable rotaxanes/catenanes.4 A conceptually dif-
ferent approach is based on the chiroptical properties of
organic compounds.5,6 Currently, chiral molecular switch-
es are considered to be the most promising systems in the
Abstract: The results presented in this paper demonstrate that the
proposed design of C2-symmetric, pentadentate achiral or chiral
ligands 8a–d and 15 allows to generate, upon coordination with
Ni(II) and Pd(II), the corresponding diastereomeric complexes pos-
sessing three new elements of chirality: stereogenic axis, center, and bottom-up approach to nanoscale information technology
helix. Of particular importance is that due to the specific steric char-
of the future. Thus, the major advantage of chiroptical
acteristics of the designed ligands the formation of the correspond-
molecular switches is the feasibility of nondestructive
ing diastereomeric products is highly stereoselective allowing
read out of optical information via, for instance, simple re-
preparation of only two out of four possible stereochemical combi-
cording of optical rotation or CD spectra.
nations. For instance, each diastereoisomeric product (Ra¢,Ph¢,Sc¢)-
9a and (Ra¢,Mh¢,Rc¢)-12a can be selectively prepared and character-
ized in solid state, simply by the choice of the chelating metal
[Ni(II) or Pd(II)]. Furthermore, introduction of stereochemical in-
formation into the ligands design with application of a simple chiral
‘Amine Module’ allows for complete transfer of the corresponding
stereochemistry to the newly generated axial, helical, and central
chirality. For example, starting with chiral ligand (R)-15, out of
One of the major issues in the design of molecular switch-
es in general, and chiroptical molecular switches in partic-
ular, is a fatigue resistance or durability of a potential
molecular devise. For instance, the most explored design6
of chiroptical molecular switches is based on the revers-
ible transformation of one optically pure diastereomer to
eight possible products, only a single product of (Rc,Ra,Ph,Sc) abso- another. Therefore, this approach has inherent disadvan-
lute configuration was obtained in the solid state. Taking into ac-
tage as the switch between diastereomers involves the
count the modular nature of this design, one may agree that
cleavage and formation of a covalent chemical bond. Tak-
modification of the three major ‘phenone’, ‘acid’, and ‘amine’ mod-
ing into account that a chemical reaction, formation of a
ules, or application of different metals, will allow for virtually un-
covalent bond, is always incomplete, the lifetime of such
molecular switches might be impractically short (less than
100 cycles).
limited structural and functional flexibility in fine-tuning the
diastereomeric relationships of this type of complexes making them
more selective and controllable by an external stimulus.
Key words: chiral molecular switches, macromolecular ligands,
nickel, palladium
To avoid these shortcomings and still to realize the prom-
ising advantage of chiroptical molecular switches, newly
emerging strategies are based on chiral conformational
switch in the conformationally restricted molecular back-
bone.7 Here,8 we would like to introduce a new idea for
the design of potential organic chiroptical molecular
switches with the mode of operation based on formation/
cleavage of metal–ligand coordination bonds.
The design and synthesis of relatively small (ideally, less
than 100 carbon atoms) organic architectures capable of
functioning as molecular memory elements for data stor-
age and information processing has recently attracted tru-
ly unprecedented attention.1,2 To date, the most successful
and well-explored approaches to the design of molecular
switches make use of chemo-mechanical properties of
macromolecular structures such as various redox systems3
Drawing inspiration from the models developed by
Borovik,9 Hamilton,10 Paequette,11 and Muthyala,12 and
building on our experience in chemistry13 and
application14 of Ni(II) complexes of amino acid Schiff
R
R
R
B
A
C
B'
A'
C
C
M
B
B'
B
B'
M
A
M
pentadentate ligand 1
A'
(Ra',Mh')-2b
A'
A
= coordination site
= d8 metal
M
(Ra',Ph')-2a
Scheme 1 General design of chiroptically switchable molecules possessing elements of axial and helical chirality
SYNTHESIS 2010, No. 1, pp 0049–0056
x
x
.
x
x
.2
0
0
9
Advanced online publication: 26.10.2009
DOI: 10.1055/s-0029-1217090; Art ID: M03709SS
© Georg Thieme Verlag Stuttgart · New York

50
V. A. Soloshonok, H. Ueki
PAPER
bases, we envisioned the design of chiroptically switch- nation bonds, represent an intriguing and admirable
able molecules presented in Scheme 1. intellectual challenge.
As one might expect, the pentadentate and achiral ligand Following the success of our modular approach15 to the
1 upon coordination with a d8 metal will produce tetraco- design of new generation of nucleophilic glycine equiva-
ordinated complexes 2a,b of square-planar geometry, lents for general asymmetric synthesis of a-amino
formed by one six-membered and two five-membered acids,15d,f we prepared the C2-symmetric pentadentate
rings. This mode of the metal chelation with coordinated ligands 8a–d using three starting structural modules, as
and noncoordinated group A and A¢, positioned up or shown in Scheme 2. The ‘phenone’ modules 3a–c were
down relatively the metal coordination plane, will create acetylated16 with ‘acid’ module 4 to give rise to the inter-
an element of axial chirality, going through the coordina- mediate amides 5a–c in quantitative chemical yield. The
tion sites B¢/B and the adjacent methylene of the corre- overall dialkylation of ‘amine’ modules 6a,b with two
sponding chelating five-membered ring. To provide for equivalents of compounds 6a–c was conducted in two
diastereomeric relationships in this design, one more ele- consecutive steps via isolation of intermediate monoalky-
ment of chirality should be incorporated into the structure lation products 7a–d. The undesirable overalkylation on
of complexes 2a,b. One of the feasible options is to create the second step, from 7a–d to 8a–d, can be completely
steric repulsive interactions in the arms BA/B¢A¢, which avoided using previously reported procedure17with appli-
will twist the six-membered chelating ring resulting in a cation of Hünig’s base. The target ligands 8a–d were thus
screw-sense of helical chirality. Furthermore, considering prepared in high isolated yield (>95%).
the expected trans-coordination of arms BA/B¢A¢, the fol-
lowing mode of motion must be realized: the noncoordi-
Br
Br
H2N
6a,b
O
NH2
O
nated site A¢ in (Ra¢,Ph¢)-2a, down relatively to the metal
coordination plane, should move up to coordinate to the
metal by uncoordinating and pushing up the site A, giving
rise to the diastereomeric complex (Ra¢,Mh¢)-2b. Conse-
quently, the reversed order of motion of site A in
(Ra¢,Mh¢)-2b will regenerate diastereomer (Ra¢,Ph¢)-2a.
This concurrent unidirectional motion of arms B¢A¢ and
AB is expected to have the following desired stereochem-
ical consequences. First, during the transformation from
(Ra¢,Ph¢)-2a to (Ra¢,Mh¢)-2b, the axial chirality on the arm
CB¢A¢ in (Ra¢,Ph¢)-2a will disappear with simultaneous
generation of new chiral axis of the same stereochemical
sense on the arm CBA in (Ra¢,Mh¢)-2b. Second, in contrast
to the retention of stereochemical sense of the axial chiral-
ity, the trans-coordination of arms CB¢A¢ and CBA to the
metal must proceed with inversion of the helical chirality
to provide for diastereomeric relationships between
(Ra¢,Ph¢)-2a and (Ra¢,Mh¢)-2b. The obvious geometric dif-
ference between these diastereomers is that the noncoor-
dinated arm CB¢A¢ and the substituent R on the
coordination site C in (Ra¢,Ph¢)-2a are on the same side of
the metal chelation plane, while in (Ra¢,Mh¢)-2b the arm
CBA and the substituent R are on the opposite sides. This
stereochemical difference between the diastereomers
(Ra¢,Ph¢)-2a and (Ra¢,Mh¢)-2b can be used as a molecular
binary logic element and potentially influenced by an ex-
ternal stimulus.
Br
R3
4
O
R1
O
NH
R2
amine module
acid module
R1
5a–c
R2
R3 = H (6a)
3a–c
R
3 = CF3 (6b)
phenone module
R1
a
b
c
Ph
H
Ph
Cl
Me
H
R2
R3
R3
H
N
O
O
O
NH
O
N
5a–c
HN
NH
R1
O
O
R2
R2
R2
R1
7a–d
8a–d
R1
a
b
c
d
R1
R2
R3
Ph
H
Ph
Cl
Me
Ph
H
H
H
H
H
CF3
Scheme 2
Ligands 8a–c are achiral, C2-symmetric and can form two
ionic and three coordination bonds, therefore the choice of
Ni(II) for chelation was quite obvious. Heating the ace-
tophenone module derived ligand 8c in acetonitrile solu-
tion and in the presence of Ni(II) resulted in formation of
the red-colored products of the expected Ni(II) complex-
es. However, the corresponding products were found to be
highly unstable and underwent noticeable decomposition
under neutral conditions. This result suggested that the
Ni(II)–carbonyl (acetyl) coordination bond is relatively
unstable9 and therefore acetophenone module 3c cannot
be used in our design.
However, the first step in this direction is to develop suit-
able molecular models which could follow this remark-
ably complex structural and stereochemical design. In
particular, the combination of the following key features,
such as: simultaneous generation of two elements of
chirality starting form achiral molecule, preference for
only one diastereomeric pair, retention of the stereochem-
ical sense of one, and the inversion of the other element of
chirality in the corresponding diastereomeric transforma-
tions via formation and cleavage of metal–ligand coordi-
In sharp contrast, the chelation of benzophenone derived
ligands 8a,b with Ni(II) resulted in the formation of stable
Synthesis 2010, No. 1, 49–56 © Thieme Stuttgart · New York

PAPER
Modular Design of Chiroptically Switchable Molecules
51
products 9a,b and 10a,b in quantitative yield (Scheme 3). phenyl rings twisted relatively to each other [C(9)–C(2)–
Compounds 9a,b and 10a,b are neutral, very well soluble C(3)–C(8)] by 40.0(7)°. It is interesting to note that in the
in polar organic solvents, have typical orange-red color structure 9a there is also the stereogenic center located on
and can be purified by column chromatography without the nitrogen [N(19)] of the benzylamine moiety. This ste-
any precautions. The observed dramatic difference in sta- reogenic center is generated by the symmetry breaking
bility between acetophenone and benzophenone derived between the stereochemically equivalent carbonyl-con-
Ni(II) complexes of this type, points to the key role of the taining arms in the starting ligand 8a upon coordination of
phenyl group, which, besides electronic effect can also one of them to the metal. Taking into account that the car-
have important steric influence protecting the Ni–O bond bonyl-coordinated arm should have higher CIP-priority,18
from any destructive interactions with nucleophilic spe- the absolute configuration of the stereogenic nitrogen is S.
1
cies. In the H NMR spectrum of compounds 9a,b and Considering the presence of these three elements of
10a,b one can observe a few relatively sharp peaks of ar- chirality in structure 9a, the formation of only one out of
omatic and extremely broadened resonances of aliphatic four possible diastereomers manifests for the remarkable,
protons, suggesting very fast interconversion between the however unexpected, success of this modular design.
diastereomers 9a,b and 10a,b. Variable temperature
1H NMR experiments revealed that this motion can be
slowed at low temperatures as indicated by noticeable
sharpening of the resonances of aliphatic protons. Howev-
er, the unambiguous characterization of the diastereomers
9a,b and 10a,b by NMR spectroscopy was not possible.
On the other hand, high stability of these compounds al-
lowed us to perform their structural characterization by X-
ray crystal structure analysis.
We found that in the solid state compounds 9a and 10a ex-
ist in a single (Ra¢,Ph¢,Sc¢)-9a diastereomeric form
(Figure 1), containing a pair of (Ra,Ph,Sc) and (Sa,Mh,Rc)
enantiomers in the crystallographic unit cell (P1 space
group). Since it is the first X-ray crystal structure of
Ni(II)-carbonyl coordinated complex of this type, a few
key characteristics should be discussed. Thus, the distanc-
es of Ni–O [1.848(4) Å] and Ni–N [1.854(4) Å] bonds, of
the same chelate six-membered ring, are noticeably short-
er than bonds between the Ni(II) and two other nitrogens
[Ni-N(30) = 1.883(4) Å; Ni–N(19) = 1.904(4) Å]. The
square-planar structure of compound 9a is slightly distort-
ed with angles N(15)–Ni–N(30) of 172.65(18)° and O(1)–
Ni–N(19) of 174.66(17)°. This deviation from planarity
gives the compound 9a a bowl-like shape and renders it
inherently chiral. Of particular importance is that the crys-
tallographic analysis confirmed the presence of two major
elements of chirality in the structure of 9a. The first is the
axial chirality located through the N(30)–C(31) bond with
the torsion angle Ni–N(30)–C(31)–C(36) of 108.0(5)°.
The second is the helical chirality generated by nonplanar
position of the Ni(II)-coordinated benzophenone moiety’s
Figure 1 X-ray crystal structure of (Ra¢,Ph¢,Sc¢)-9a
Encouraged by these results, we prepared, using the same
conditions, the complexes 11a,b and 12a,b, containing
Pd(II). These compounds are also neutral and very well
soluble in polar organic solvents and have characteristic
yellow-orange color. Purification of products 11a,b and
12a,b can be easily conducted via regular column chro-
1
matography. The H NMR spectroscopic data for com-
pounds 11a,b and 12a,b are very similar to those
described for diastereomers 9a,b and 10a,b showing
broadened resonances of aliphatic protons. Therefore for
characterization of these derivatives we conducted crys-
tallographic studies.
O
O
O
O
O
O
N
N
N
N
N
HN
N
N
M
NH
M
Ni(II) or
Pd(II)
O
O
O
+
O
O
O
R
R
R
R
R
R
(Ra',Mh',Rc')-10a,b; M = Ni
(Ra',Mh',Rc')-12a,b; M = Pd
8a,b
R = H (a), Cl (b)
(Ra',Ph',Sc')-9a,b; M = Ni
(Ra',Ph',Sc')-11a,b; M = Pd
Scheme 3
Synthesis 2010, No. 1, 49–56 © Thieme Stuttgart · New York

52
V. A. Soloshonok, H. Ueki
PAPER
In sharp contrast to the Ni(II)-containing complex 9a, the sterically congested structure of the designed ligands 8 the
crystallographic unit cell of 12a (Figure 2) has P21/c formation of the corresponding diastereomeric products is
space group containing four molecules. Most unexpected- highly stereoselective allowing preparation of only two
ly, we found that in the solid state these compounds exist out of four possible stereochemical combinations. Fur-
in a single (Ra¢,Mh¢,Rc¢)-12a diastereomeric form [two thermore each diastereoisomeric product (Ra¢,Ph¢Sc¢)-9a
pairs of (Ra,Mh,Rc) and (Sa,Ph,Sc) enantiomers]. The dis- and (Ra¢,Mh¢Rc¢)-12a can be selectively prepared and char-
tances of Pd–O and Pd–N bonds are, as they should be, acterized in solid state, simply by the choice of the chelat-
longer as compared with the 9a, however the trend that ing metal.
Pd–O [1.9798(16) Å] and Pd–N [1.987(2) Å] bonds, of
Based on these results, and as the next logical step, we de-
the same chelate ring, are noticeably shorter than bonds
cided to explore a possibility of preparation of this new
between the Pd(II) and two other nitrogens [Pd–
type of complexes in enantiomerically pure form. Taking
N(30) = 2.018(2) Å; Pd–N(19) = 1.9966(19) Å] was
advantage of the modular nature of our design we used the
found to be the same. The square-planar structure of com-
same synthetic approach as discussed in Scheme 3, with
pound 12a is also distorted, of bowl-like shape, with the
the difference that chiral amine module (R)-13 was ap-
angles N(15)–Pd–N(30) of 170.03(8)° and O(1)–Pd–
plied for the alkylation step. As shown in Scheme 4 the
N(19) of 177.91(7)°, rendering it inherently chiral. Simi-
bis-alkylation of (R)-13, via intermediate (R)-14, gave
chiral, yet C2-symmetric ligand (R)-15. Heating an aceto-
nitrile solution of (R)-15 in the presence of Pd(II) resulted
in the formation of yellow-orange colored diastereomeric
products (Rc,Ra,Ph,Sc)-16 and (Rc,Ra,Mh,Rc)-17. These
products were carefully purified by column chromatogra-
phy on silica gel. Analysis of the reaction mixture by TLC
using various eluent mixtures confirmed the presence of
larly to the structure of 9a, compound 12a has three ele-
ments of chirality. The axial chirality is directed along the
N(30)–C(31) bond with torsion angle Pd–N(30)–C(31)–
C(36) of 55.9(3)°, which is substantially different from
that of Ni(II) complex 9a, however of the same R config-
uration. The helical chirality in 12a is generated by the
screw-like twisting of the coordinated benzophenone
moiety’s phenyl rings. The corresponding torsion angle
only a single colored spot, clearly manifesting that the ste-
[C(9)–C(2)–C(3)–C(8)] of –44.8(3)° is close in magni-
reochemical information of the stereogenic center in start-
tude to that of Ni(II) containing complex 9a, however dif-
ing ligand (R)-15 was quantitatively transferred to the
three newly created elements of chirality: stereogenic
axis, center and helix. Unfortunately, characterization of
diastereomeric products 16 and 17 by NMR spectroscopy
ferent in sign and has M absolute configuration. The
stereogenic center, located on the nitrogen [N(19)] of the
benzylamine moiety, is also of the different absolute con-
figuration R, as compared with that of Ni(II) complex 9a.
was not possible due to the fast interconversion between
them.
Crystallographic analysis of the products revealed the
presence in a solid state diastereo- and enantiomerically
pure compound (Rc,Ra,Ph,Sc)-16 (Figure 3) crystallizing
in hexagonal chiral space group P61. In sharp contrast to
the trend observed in two previous cases compounds 9a
(Figure 1) and 12a (Figure 2), the distance of the Pd–N(1)
bond, in the six-membered chelate ring, was noticeably
shorter than Pd–O(1) [2.003(3) Å], Pd–N(3) [2.008(4) Å]
Figure 2 X-ray crystal structure of (Ra¢,Mh¢,Rc¢)-12a
Analysis of these crystallographic results undoubtedly
confirmed the basic assumption of our design that the co-
ordination of achiral, pentadentate ligand with metal can
result in generation of diastereomeric relationships with
at least two elements of chirality. Moreover, due to the
Figure 3 X-ray crystal structure of (Rc,Ra,Ph,Sc)-16
Synthesis 2010, No. 1, 49–56 © Thieme Stuttgart · New York

PAPER
Modular Design of Chiroptically Switchable Molecules
53
H
N
Ph
O
O
H2N
O
N
O
NH
(R)-13
HN
NH
amine module
5a
Ph
5a
O
O
(R)-14
(R)-15
O
O
O
O
N
Pd
O
N
Pd
O
N
N
+
N
N
Pd(II)
O
O
(Rc,Ra,Ph,Sc)-16
(Rc,Ra,Mh,Rc)-17
Scheme 4
and Pd–N(2) [1.999(4) Å]. On the other hand the square- (Rc,Ra,Ph,Sc) absolute configuration was obtained in a sol-
planar coordination plane in compound 16 was similarly id state. Taking into account the modular nature of this de-
distorted, providing for the bowl-like shape, with the sign, one may agree that modification of the three major
angles N(1)–Pd–N(3) of 170.6(2)° and N(2)–Pd–O(1) of ‘phenone’, ‘acid’, and ‘amine’ modules, or application of
174.30(16)°.
different metals, will allow for virtually unlimited struc-
tural and functional flexibility in fine-tuning the diastere-
omeric relationships of this type of complexes making
them more selective and controllable by an external stim-
ulus.
In this case the complex of 16 has four elements of chiral-
ity. The chiral axis of R absolute configuration, is directed
along of the N(3)–C(26) bond with torsion angle Pd–
N(3)–C(26)–C(27) of –55.3(6)°. Similarly to the previous
cases, the P helical chirality in 16 is generated by the
twisting of the benzophenone moiety’s phenyl rings by
33.8(7)° [C(6)–C(7)–C(8)–C(9)]. The newly generated
stereogenic center, located on the nitrogen [N(2)] was
found to be of S absolute configuration.
1H, 13C, and 19F NMR were performed on Varian Unity-300 (299.94
MHz) and Gemini-200 (199.98 MHz) spectrometers using TMS,
CDCl3, and CCl3F as internal standards, respectively. High-resolu-
tion mass spectra (HRMS) were recorded on a Jeol HX110A instru-
ment. Optical rotations were measured on a Jasco P-1010
polarimeter. Melting points are uncorrected and were obtained in
open capillaries. All reagents and solvents, unless otherwise stated,
are commercially available and were used as received. Unless oth-
erwise stated, yields refer to isolated yields of products of greater
than 95% purity as estimated by 1H, 19F, and 13C NMR spectrome-
As it follows from the results obtained, the proposed de-
sign of C2-symmetric, pentadentate achiral 8a–d and
chiral ligands 15 allows to generate, upon coordination
with Ni(II) and Pd(II), the corresponding diastereomeric
complexes possessing three new elements of chirality:
stereogenic axis, center, and helix. Of particular impor-
tance is that due to the specific steric characteristics of the
designed ligands the formation of the corresponding dia-
stereomeric products is highly stereoselective allowing
preparation of only two out of four possible stereochemi-
cal combinations. For instance, each diastereoisomeric
product (Ra¢,Ph¢Sc¢)-9a and (Ra¢,Mh¢Rc¢)-12a can be selec-
tively prepared and characterized in solid state, simply by
the choice of the chelating metal. Furthermore, introduc-
tion of stereochemical information into the ligands design
with application of a simple chiral ‘amine module’ allows
for complete transfer of the corresponding stereochemis-
try to the newly generated axial, helical and central chiral-
ity. For example, starting with chiral ligand (R)-15, out of
eight possible products, only a single product 16 of
1
try. All new compounds were characterized by H, 19F, 13C NMR
and HRMS.
The preparation of 5a,c is described in the literature.16 Compound
5b was prepared following the described procedure.16 Compounds
7a–d and 14 were prepared according to the procedure described in
the literature.16,17
5b
Mp 125.5 °C.
1H NMR: d = 4.02 (2 H, s), 7.45–7.80 (7 H, m), 8.53–8.64 (2 H, m),
11.3 (1 H, br s).
13C NMR: d = 29.3, 123.0, 125.4, 128.3, 128.6, 130.0, 132.6, 133.1,
133.8, 137.5, 137.9, 164.9, 197.9.
HRMS: m/z calcd for C15H11BrClNO2 + Na [M + Na+]: 373.9559;
found: 373.9527.
Synthesis 2010, No. 1, 49–56 © Thieme Stuttgart · New York

54
V. A. Soloshonok, H. Ueki
PAPER
7a
8a
Mp 69.8 °C.
Mp 81.5 °C.
1H NMR: d = 3.46 (2 H, s), 3.87 (2 H, s), 7.12 (1 H, ddd, J = 7.91,
7.31, 1.17 Hz), 7.20–7.65 (11 H, m), 7.74–7.85 (2 H, m), 8.65 (1 H,
dd, J = 8.30, 0.88 Hz), 11.7 (1 H, br s).
1H NMR: d = 3.32 (4 H, s), 3.78 (2 H, s), 7.08–7.20 (5 H, m), 7.34–
7.45 (6 H, m), 7.45–7.60 (6 H, m), 7.62–7.68 (4 H, m), 8.24–8.32 (2
H, m), 11.0 (1 H, br s).
13C NMR: d = 52.7, 53.9, 121.6, 122.3, 124.8, 127.3, 128.3, 128.4,
128.5, 130.1, 132.6, 132.8, 133.6, 138.5, 139.1, 139.2, 171.3, 198.4.
13C NMR: d = 59.1, 59.6, 122.6, 123.2, 126.6, 127.8, 128.2, 128.4,
129.7, 130.0, 132.4, 132.5, 133.3, 136.1, 138.1, 138.3, 169.2, 198.1.
HRMS: m/z calcd for C22H20N2O2 + Na [M + Na+]: 367.1422;
HRMS: m/z calcd for C37H31N3O4 + Na [M + Na+]: 604.2212;
found: 367.1396.
found: 604.2204.
7b
8b
Mp 119.0 °C.
Mp 111.8 °C.
1H NMR: d = 3.44 (2 H, s), 3.85 (2 H, s), 7.16–7.34 (3 H, m), 7.37–
7.44 (2 H, m), 7.45–7.58 (4 H, m), 7.60–7.68 (1 H, m), 7.75–7.83 (2
H, m), 8.63 (1 H, dd, J = 8.79, 0.49 Hz), 11.6 (1 H, br s).
1H NMR: d = 3.31 (4 H, s), 3.75 (2 H, s), 7.09–7.21 (3 H, m), 7.33–
7.48 (10 H, m), 7.54–7.65 (6 H, m), 8.23 (2 H, d, J = 8.79 Hz), 10.8
(2 H, br s).
13C NMR: d = 52.6, 54.0, 123.1, 126.2, 127.3, 127.4, 128.4, 128.5,
128.5, 130.1, 131.9, 133.1, 133.3, 137.7, 139.0, 171.3, 197.0.
13C NMR: d = 59.3, 59.9, 124.1, 127.8, 127.9, 128.4, 128.4, 128.5,
129.7, 130.0, 131.6, 133.0, 133.0, 135.8, 136.8, 137.3, 169.0, 196.8.
HRMS: m/z calcd for C22H20ClN2O2 [M + H+]: 379.1213; found:
HRMS: m/z calcd for C37H30Cl2N3O4 [M + H+]: 650.1613; found:
379.1207.
650.1519.
7c
8c
Mp 85.0 °C.
Mp 99.0 °C.
1H NMR: d = 2.64 (3 H, s), 3.44 (2 H, s), 3.87 (2 H, s), 7.09 (1 H,
dddd, J = 7.91, 7.33, 1.17, 0.59 Hz), 7.13–7.38 (3 H, m), 7.40–7.57
(3 H, m), 7.85 (1 H, dd, J = 8.00, 1.56 Hz), 8.80 (1 H, dd, J = 8.50,
1.17 Hz), 12.5 (1 H, br s).
1H NMR: d = 2.59 (6 H, s), 3.61 (4 H, s), 4.09 (2 H, s), 7.09 (2 H,
ddd, J = 7.91, 7.33, 1.17 Hz), 7.20–7.35 (3 H, m), 7.42–7.58 (4 H,
m), 7.83 (2 H, dd, J = 8.01, 1.66 Hz), 8.69 (2 H, dd, J = 8.50 Hz),
12.0 (2 H, br s).
13C NMR: d = 28.4, 53.0, 53.7, 120.7, 122.3, 122.5, 127.0, 128.1,
128.3, 131.3, 134.5, 139.2, 139.8, 171.5, 201.6.
13C NMR: d = 28.3, 58.2, 59.2, 120.9, 122.4, 122.7, 127.4, 128.2,
129.4, 131.1, 134.4, 136.9, 139.7, 169.8, 201.7.
HRMS: m/z calcd for C17H19N2O2 [M + H+]: 283.1447; found:
HRMS: m/z calcd for C27H27N3O4 + Na [M + Na+]: 480.1899;
283.1465.
found: 480.1839.
7d
8d
Mp 121.0 °C.
Mp 70.5 °C.
1H NMR: d = 3.40 (2 H, s), 3.83 (2 H, s), 7.04 (1 H, m), 7.30–7.66
(9 H, m), 7.68–7.80 (2 H, m), 8.67 (1 H, m), 11.7 (1 H, br s).
1H NMR: d = 3.41 (4 H, s), 3.89 (2 H, s), 7.12 (2 H, m), 7.24–7.88
(18 H, m), 8.32 (2 H, d, J = 8.59 Hz), 11.1 (2 H, br s).
13C NMR: d = 52.6, 53.0, 121.1, 121.9, 123.9 (q, J = 272.1 Hz),
124.2, 124.8 (q, J = 3.74 Hz), 127.9, 128.3, 128.9 (q, J = 32.2 Hz),
129.7, 132.3, 132.4, 138.0, 138.9, 143.1 (q, J = 1.44 Hz), 170.6,
198.0.
13C NMR: d = 59.0, 122.1, 122.9, 123.8 (q, J = 272.4 Hz), 125.1 (q,
J = 3.84 Hz), 125.9, 128.0, 129.5 (q, J = 32.2 Hz), 129.7, 129.8,
132.2, 132.4, 133.2, 137.8, 138.2, 140.4 (q, J = 1.53 Hz), 168.7,
198.0.
19F NMR: d = 99.6 (s).
HRMS: m/z calcd for C23H19F3N2O2 + Na [M + Na+]: 435.1226;
19F NMR: d = 99.2 (s).
HRMS: m/z calcd for C38H31F3N3O4 [M + H+]: 650.2267; found:
found: 435.1228.
650.2258.
14
Complexes 9a, 12a, and 16; General Procedure
Mp 114.0 °C; [a]D25 –21.3 (c 2.85, CHCl3).
Ligands 8a–d were heated (50 °C) in MeCN in the presence of
Ni(II) or Pd(II) (nitrates, chlorides). Upon complete consumption of
starting compound 8 (monitoring by TLC), the solvent was evapo-
rated and the target complexes were isolated by column chromatog-
raphy (CHCl3–acetone, 5:1).
1H NMR: d = 1.43 (3 H, d, J = 6.45 Hz), 3.13 (1 H, d, J = 17.6 Hz),
3.31 (1 H, d, J = 17.6 Hz), 3.76 (1 H, q, J = 6.45 Hz), 7.03 (1 H, m),
7.10–7.59 (10 H, m), 7.72–7.82 (2 H, m), 8.66 (1 H, m), 11.7 (1 H,
br s).
13C NMR: d = 23.5, 51.0, 58.2, 121.2, 121.9, 124.6, 126.5, 126.9,
128.0, 128.2, 129.8, 132.3, 132.3, 133.2, 138.2, 138.9, 144.2, 171.4,
197.8.
HRMS: m/z calcd for C23H23N2O2 [M + H+]: 359.1760; found:
359.1717.
9a
Mp 223.8 °C (dec.).
HRMS: m/z calcd for C37H29N3NiO4 + Na [M + Na+]: 660.1409;
found: 660.1424.
12a
Ligands 8a–d; General Procedure
Mp 163.9 °C (dec.).
Compounds 7a–d (1 equiv) were heated (50 °C) in MeCN with bro-
mides 5a–c (1 equiv) in the presence of Hünig’s base (2 equiv). The
reaction was monitored by TLC and upon completion (~24 h) the
solvent was evaporated and the target products were isolated by col-
umn chromatography (hexane–EtOAc, 4:1).
HRMS: m/z calcd for C37H29N3O4Pd + Na [M + Na+]: 708.1091;
found: 708.1155.
16
Mp 248.9 °C (dec.); [a]D25 +75.2 (c 0.45, CHCl3).
Synthesis 2010, No. 1, 49–56 © Thieme Stuttgart · New York

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Modular Design of Chiroptically Switchable Molecules
55
HRMS: m/z calcd for C38H31N3O4Pd + Na [M + Na+]: 722.1247;
found: 722.1331.
2001, 249. (m) Ambroise, A.; Wagner, R. W.; Rao, P. D.;
Riggs, J. A.; Hascoat, P.; Diers, J. R.; Seth, J.; Lammi, R. K.;
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13, 1023.
15
Compound 15 was prepared according to the general procedure de-
scribed for 8a–d.
Mp 68.2 °C; [a]D25 +4.26 (c 1.01, CHCl3).
1H NMR: d = 1.50 (3 H, d, J = 6.74 Hz), 3.27 (2 H, d, J = 16.7 Hz),
3.45 (2 H, d, J = 16.7 Hz), 4.12 (1 H, q, J = 6.74 Hz), 7.10–7.28 (5
H, m), 7.35–7.80 (16 H, m), 8.36 (2 H, m), 11.0 (2 H, br s).
13C NMR: d = 18.5, 56.8, 61.2, 122.4, 122.9, 126.2, 127.6, 128.1,
128.2, 128.4, 130.0, 132.4, 132.5, 133.3, 138.1, 138.5, 140.8, 170.0,
198.1.
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Acknowledgment
The work was supported by the Department of Chemistry and Bio-
chemistry, University of Oklahoma. The authors thank the National
Science Foundation (grant CHE-0130835) for funds to purchase the
X-ray instrument and computers. The crystallographic studies were
performed by Dr. D. R. Powell. The authors gratefully acknowledge
generous financial support from Central Glass Company (Tokyo,
Japan) and Ajinomoto Company (Tokyo, Japan). Help of Drs. J. L.
Moore and T. K. Ellis with some experiments is gratefully acknow-
ledged.
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Synthesis 2010, No. 1, 49–56 © Thieme Stuttgart · New York