The selective formation of neutral, heteroleptic zinc(II) complexes via self-discrimination of chiral bisoxazoline racemates and pseudoracemates

Article abstract of DOI:10.1039/b413439g

The reversible metal-directed multi-component self-assembly of chiral bisoxazolines proceeds with a high level of chiral self-discrimination and thus defines a simple strategy for the preparation of neutral, heteroleptic zinc(II) complexes. The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2005.

Full text of DOI:10.1039/b413439g

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L E T T E R
The selective formation of neutral, heteroleptic zinc(II) complexes
via self-discrimination of chiral bisoxazoline racemates and
pseudoracematesw
James M. Takacs,* Paul M. Hrvatin, Jeffery M. Atkins, D. Sahadeva Reddy and
Joanna L. Clark
Department of Chemistry and Center for Materials Research and Analysis, University of
Nebraska-Lincoln, Lincoln, Nebraska 68588-0304, USA. E-mail: jtakacs1@unl.edu;
Fax: +1-402-472-9402; Tel: +1-402-472-6232
Received (in St Louis, MO, USA) 1st September 2004, Accepted 27th November 2004
First published as an Advance Article on the web 11th January 2005
The reversible metal-directed multi-component self-assembly
of chiral bisoxazolines proceeds with a high level of chiral self-
discrimination and thus defines a simple strategy for the pre-
paration of neutral, heteroleptic zinc(II) complexes.
dral coordination geometry of zinc(II) strongly favors self-
discrimination in this case: only the neutral, heterochiral
complex (S,R)-3 is observed.
Fig. 1 compares the 3.3–5.3 ppm region of the 600 MHz 1H
NMR spectrum (CDCl3) for the free box ligand 1 to those of
the heterochiral [(S,R)-3] and homochiral [(R,R)-2] complexes.
Overall, the spectra show that the homochiral and heterochiral
complexes are distinctly different in solution, and at the level of
NMR detection, the combination of (4S,40S)-1 and (4R,40R)-1
with Zn(OAc)2 affords exclusively the heterochiral complex. Of
particular note in the spectrum of (S,R)-3 is the dramatic
upfield shift for the hydrogen on the phenyl-bearing carbon
of the dihydrooxazole ring (Ha; see structure 1, Scheme 1). It is
highly shielded in the heterochiral complex relative to the free
ligand or homochiral complex. In addition, it is worth noting
the resonances for (R,R)-2 are somewhat broadened, indicative
of possible dynamic behavior.
Developing strategies to predictably connect different sub-
units under reversible conditions is important for program-
ming the multi-component self-assembly of supramolecules,1
particularly as it relates to the design of functional materials
such as catalysts,2 sensors, and molecular machines. Two
approaches are often employed to direct multi-component
self-assembly:3 self-recognition4 or self-discrimination.5 These
are typically reduced to practice by constructing pairs of
complementary hydrogen-bonding motifs6 or pairs of ligands
possessing complementary steric or electronic motifs to bias
their assembly.7 We are interested in exploiting metal-directed
multi-component self-assembly for the formation of chiral,
heteroleptic complexes in the design of new heterobimetallic
asymmetric catalyst systems.8
Schmittel and co-workers have paired unhindered 1,10-
phenanthrolines with sterically encumbered ones for the very
successful self-assembly of cationic, heteroleptic copper(I) and
silver(I) complexes.9 We have explored an alternative approach
to prepare neutral, heteroleptic zinc(II) complexes, using the
complementary chirality of bisoxazoline (box) ligands to direct
their assembly. Chiral ligands have been widely used to control
metal-centered and helical chirality in self-assembled metal
complexes and in some cases to direct self-sorting.10
The neutral, heterochiral zinc complexes are proving to be
quite remarkable compounds. Complexation is reversible in
the presence of a proton source; for example, adding another
(R)- or (S)-box derivative leads to rapid substitution, while a
mixture of homochiral complexes rapidly disproportionates to
the heterochiral complex (Scheme 2) as judged by 1H NMR.11
The complexes are typically freely soluble in a variety of
The neutral, homochiral complex (R,R)-2 is formed by
stirring 2 equiv. of (4R,40R)-1 with Zn(OAc)2 (Scheme 1).z
Zn(OAc)2 serves a dual role in the reaction, simultaneously
delivering the metal center and the required base. However,
when a racemic mixture of box ligands [i.e., 1 equiv. each of
(4S,40S)-1 and (4R,40R)-1] is combined with Zn(OAc)2, three
complexes can form: the homochiral complexes (S,S)- and
(R,R)-2 (i.e., chiral self-recognition) and/or the heterochiral
complex (S,R)-3 (i.e., chiral self-discrimination). The tetrahe-
w Electronic supplementary information (ESI) available: full experi-
mental details for complexes (S,S)-2, (S,R)-3 and 6, including structure
determination procedures and 1H and 13C NMR spectra (plus NMR
spectra of the free ligands); preparation procedure for (R,R)-5. See
http://www.rsc.org/suppdata/nj/b4/b413439g/
z Both the homochiral complex 2 [colorless solid; mp 185–186 1C (with
decomposition)] and the heterochiral complex (S,R)-3 [colorless solid;
mp 271–276 1C (with decomposition)] form quantitatively and are
obtained as solids upon removal of CH2Cl2 and trituration; the yields
given in Scheme 1 largely reflect mechanical losses.
Scheme 1 Synthetic scheme of the facile preparation of neutral
(box)2Zn complexes.
T h i s j o u r n a l i s & T h e R o y a l S o c i e t y o f C h e m i s t r y a n d t h e
C e n t r e N a t i o n a l d e l a R e c h e r c h e S c i e n t i f i q u e 2 0 0 5
N e w J . C h e m . , 2 0 0 5 , 2 9 , 2 6 3 – 2 6 5
263

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Scheme 2 Facile disproportionation of a mixture of homochiral
complexes and H/D exchange of the heterochiral (S,R)-3.
complex (S,R)-3 so as to shield the hydrogen on the phenyl-
bearing carbon of the dihydrooxazole ring (Ha).
Fig. 1 The 3.3–5.3 ppm region of the 600 MHz 1H NMR spectrum
(CDCl3) for the free box ligand (4S,40S)-1, the homochiral complex
(R,R)-2 and the heterochiral complex (S,R)-3. See structure 1 for the
identities of Ha–Hc; assignments are based on decoupling and NOE
experiments.
Heterochiral complexes such as (S,R)-3 are meso by inver-
sion symmetry and hence achiral. Nevertheless, the process of
chiral self-discrimination is inherently one of heteroleptic self-
assembly (i.e., non-identical groups bond to the metal) and
should not be restricted to pairs of enantiomers. Pseudo-
enantiomers could combine similarly to afford complexes
lacking a center of inversion. To illustrate the idea and its
potential versatility for preparing chiral, heteroleptic com-
plexes, the pseudo-racemic combination (4S,40S)-4 and
(4R,40R)-5 was used to prepare the mixed cyano/benzyl-sub-
stituted complex 6 (Fig. 3). The heteroleptic complex forms
exclusively as judged by NMR. In spite of the complementary
chirality of the box moieties, complex 6 lacks inversion sym-
metry and is chiral, for example, exhibiting a large optical
rotation, [a]D = ꢀ2031 (c = 0.75, CH2Cl2).
moderately polar organic solvents (e.g., CH2Cl2, CHCl3, THF,
and toluene) and partially soluble in methanol. They are stable
toward water but insoluble. However, the complexes are not
completely inert toward protic solvents as evidenced, for
example, by rapid H/D exchange. Adding CD3OD to a solu-
tion of (S,R)-3 (CD2Cl2) shows complete H/D exchange within
the time the NMR spectrum can be recorded.
Box-metal complexes have been widely investigated due to
their successful use in asymmetric catalysis and the observation
of nonlinear effects.12 Both homochiral and heterochiral ca-
tionic complexes have been reported by others, including a
tetrahedral zinc complex from isopropylidene box deriva-
tives,13 and several octahedral complexes derived from box14
or pybox15 ligands. The crystal structure of one neutral,
homochiral complex has been reported.16 To better understand
the factors favoring self-discrimination over self-recognition,
we grew crystals of (S,R)-3 and (S,S)-2 and determined their
structures by X-ray analysis (Fig. 2).y
The heterochiral complex (S,R)-3 exhibits near-perfect tetra-
hedral coordination while the homochiral complex (S,S)-2, for
which there are two closely related conformers in the unit cell,
distorts from tetrahedral coordination to minimize steric inter-
actions between the phenyl substituents of the two box ligands.
Otherwise, the selected bond lengths and angles summarized in
Table 1 show little variation between the two complexes. The
crystal structures are consistent with the NMR data, particu-
larly the positioning of the phenyl groups in the heterochiral
Fig. 2 The crystal structures of (S,S)-2 (left) and (S,R)-3 (right).
Table 1 Selected bond lengths (A) and angles (1) in (S,S)-2 and
(S,R)-3
(S,S)-2
(conformer a)a
(S,S)-2
(conformer b)a
y CCDC reference numbers 245214–245216. See http://www.rsc.org/
suppdata/nj/b4/b413439g/ for crystallographic data in .cif or other
electronic format. Crystal data for compound (S,S)-2: C38H34N4O4Zn,
orthorhombic, a = 10.2844(5), b = 16.5841(8), c = 75.389(4) A,
U = 12 858(1) A3, T = 100(2) K, space group C2221 (no. 20), Z = 16,
m(MoKa) = 0.812 mmꢀ1, 60 061 reflections measured, 13 131 unique
(Rint = 0.0519). The final R1 and wR2 were 0.0524 and 0.1037 for
12 539 reflections with I 4 2s(I). Crystal data for compound (S,R)-3:
C38H34N4O4Zn, monoclinic, data were reduced and the cell determined
via the software MARXDS (MarResearch), a = 17.205(3), b =
10.733(2), c = 18.407(4) A, b = 105.98(3) 1, U = 3267.7(11) A3,
T = 298(2) K, space group P21/c (no. 14), Z = 4, m(MoKa) = 0.799
mmꢀ1, 16 914 reflections measured, 5045 unique (Rint = 0.335). The
final R1 and wR2 were 0.0549 and 0.1408 for 4114 reflections with
I 4 2s(I). Crystal data for compound 6: C92H78N10O8Zn2, triclinic,
a = 10.7889(6), b = 10.8866(6), c = 17.2241(9) A, a = 73.146 (1)1,
b = 88.623(1)1, g = 86.943(1)1, U = 1933.3(2) A3, T = 100(2) K,
space group P1 (no. 1), Z = 1, m(MoKa) = 0.687 mmꢀ1, 23 488
reflections measured, 17 235 unique (Rint = 0.0164). The final R1 and
wR2 were 0.0378 and 0.0903 for 16 737 reflections with I 4 2s(I).
(S,R)-3
N1–Zn–N2
N3–Zn–N4
Zn–N1
Zn–N2
Zn–N3
Zn–N4
N1–C3
N2–C5
N3–C10
N4–C12
C3–C4
93.83
95.05
93.99
92.34
94.21
93.56
1.988(3)
1.967(3)
1.999(3)
1.965(3)
1.310(5)
1.313(5)
1.303(5)
1.305(5)
1.394(6)
1.396(6)
1.403(6)
1.393(7)
2.005(3)
1.948(3)
2.018(3)
1.968(3)
1.295(5)
1.323(5)
1.304(5)
1.306(5)
1.398(6)
1.387(6)
1.402(6)
1.388(6)
1.971(3)
1.973(3)
1.975(3)
1.976(3)
1.303(4)
1.311(5)
1.316(4)
1.292(4)
1.392(5)
1.386(6)
1.371(5)
1.396(6)
C4–C5
C10–C11
C11–C12
a
Two conformers of (S,S)-2 are present in the unit cell.
264
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Acknowledgements
Financial support from the University of Nebraska Research
Initiative is gratefully acknowledged. We thank the NSF
(CHE-0091975) and UNL CMRA for funds for the purchase
of the diffractometer, the NSF (CHE-0091975, MRI-0079750)
and NIH (SIG-1-510-RR-06307) for funding to purchase the
NMR spectrometers used in these studies, and Drs John
Desper and Tom Brett for assistance in obtaining crystal
structures.
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