Unprecedented diastereoselective generation of chiral-at-metal, half sandwich Ir(iii) and Rh(iii) complexes via anomeric isomerism on "sugar-coated" N-heterocyclic carbene ligands

Article abstract of DOI:10.1039/c0dt01634a

The first example of the diastereoselective synthesis induced by anomeric isomerism of sugar units in ligands of metal complexes was demonstrated. S and R configurations of chiral-at-metal Ir(iii) and Rh(iii) complexes were selectively obtained by using chelate-type NHC ligands with α- and β-glucopyranosyl units, respectively.

Full text of DOI:10.1039/c0dt01634a

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Unprecedented diastereoselective generation of chiral-at-metal, half sandwich
Ir(III) and Rh(III) complexes via anomeric isomerism on “sugar-coated”
N-heterocyclic carbene ligands†‡
Teppei Shibata,a Hideki Hashimoto,b,c,d Isamu Kinoshita,a,c,d Shigenobu Yanod,e and Takanori Nishioka*a,c
Received 24th November 2010, Accepted 9th March 2011
DOI: 10.1039/c0dt01634a
The first example of the diastereoselective synthesis induced
by anomeric isomerism of sugar units in ligands of metal
complexes was demonstrated. S and R configurations of
chiral-at-metal Ir(III) and Rh(III) complexes were selectively
obtained by using chelate-type NHC ligands with a- and b-
glucopyranosyl units, respectively.
In the case of Ru and Mn cyclopentadienyl complexes with
phosphine ligands,4 16-electron intermediates, generated by dis-
sociation of one of the ligands, have pyramidal structures whose
chirality is inverted through a trigonal planar structure with higher
energy. Although in the case of chiral-at-metal NHC complexes,
the mechanisms for generation and inversion of the chirality are
probably similar to those for phosphine complexes, the differences
in the nature of NHCs and phosphines, such as s-donating and p-
accepting abilities, should affect the mechanisms. Use of sterically
demanding chiral substituents on NHC ligands will be useful for
investigating the mechanisms.
Controlling the chirality around a metal center in chiral-at-
metal complexes1 is important for preparing effective asymmetric
catalysts. Using chiral organic functional groups is the most useful
method for synthesizing chiral catalysts.2
Sugars, especially D-glucose, are excellent candidates for use as
chiral sources because they are the most abundant bioresource
in nature.5 We previously synthesized the first example of sugar-
coated NHC complexes.6 When an anomeric carbon is directly
attached to an imidazolylidene nitrogen, a- or b-glucosides can
be isolated. Use of the steric effects attributed to the anomers
of D-glucopyranosyl units would be an excellent approach to
controlling the absolute conformation of metal complexes. The
combination of the chirality and the anomeric isomerism of glu-
cose should produce sufficient environments in metal complexes
for such a purpose. We report here incorporation of a- and b-
AcGlc groups into chelate-type NHC ligand precursors, which
were used for diastereoselective syntheses of chiral-at-metal half-
sandwich Ir(III) and Rh(III) complexes. In other words, to the best
of our knowledge, this is the first report of controlling chirality
using anomeric isomerism of sugars.
Although phosphine ligands have mostly been used in this area,
chiral N-heterocyclic carbene (NHC) ligands have started to be
used in recent years.3 From our approach using metal complexes
with anomeric isomers of sugar units, we have observed kinetic
and thermodynamical discrimination of the chiral-at-metal center,
which demonstrates the important role of anomeric isomerism of
sugars in controlling the chirality of metal complexes.
aDepartment of Chemistry, Graduate School of Science, Osaka City
University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka, 558-8585, Japan.
E-mail: nishioka@sci.osaka-cu.ac.jp; Fax: +81 6 6690 2753; Tel: +81 6
6605 2569
bDepartment of Physics, Graduate School of Science, Osaka City University,
Osaka, Japan
cCREST, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi,
Saitama, 332-0012, Japan
dThe OCU Advanced Research Institute for Natural Science and Technology
(OCARINA), Osaka City University, Osaka, Japan
Ir(III) and Rh(III) complexes were produced via a carbene
transfer reaction7 using silver NHC complexes 3a or 3b, which
were obtained quantitatively by reacting Ag2O with 2a and 2b,
respectively (Scheme 1). From 1H NMR spectroscopy, 3a and 3b
were consumed completely within 5 min, and the Ir(III) and Rh(III)
complexes formed almost quantitatively. In the 1H NMR spectra
of the final products, only two sets of the signals for the Cp* and
sugar-coated NHC ligands with ratios of 95 : 5 for Ir4a, 85 : 15
for Ir4b, 90 : 10 for Rh4a, and 85 : 15 for Rh4b were observed.
These results suggest that the produced Ir and Rh complexes have
two diastereomers due to the pseudo-tetrahedral structure around
the metal center. The major diastereomers of Ir4b and Rh4b,
eGraduate School of Materials Science, Nara Institute of Science and
Technology (NAIST), Takayama, Ikoma, Nara, 630-0192, Japan
† Electronic supplementary information (ESI) available: Full experimental
procedures and data for 1a, 1b, 2aHCl, 2bHCl, 3a, 3b, Ir4a, Ir4b, Rh4a,
and Rh4b. CCDC reference numbers 796414 and 796415 for Ir and Rh
complexes, respectively. For ESI and crystallographic data in CIF or other
electronic format see DOI: 10.1039/c0dt01634a
‡ Crystal data for R-Ir4b-PF6·2CH3OH·H2O: C35H52ClF6IrN3O12P, Mr =
˚
1079.44, orthorhombic, space group P212121 (no. 19), a = 12.6224(13) A,
3
˚
˚
˚
b = 15.2989(18) A, c = 22.254(3) A, V = 4297.4(9) A , Z = 4, T = 193(1) K,
Dcalcd = 1.668 g cm-3, reflections collected 42 049, independent reflections
9707, Rint = 0.069, R1 = 0.0455 (I > 2s(I)), wR2 = 0.0968 (all data), GOF =
1.002, Flack parameter = 0.051(7). Crystal data for R-Rh4b-PF6·CH2Cl2:
C34H44Cl3F6N3O9PRh, Mr = 992.96, orthorhombic, space group P212121
˚
˚
˚
-
(no. 19), a = 12.5638(7) A, b = 15.2175(9) A, c = 22.2295(14) A, V =
isolated by fractional crystallization of the corresponding PF6
4250.0(4) A , Z = 4, T = 193(1) K, Dcalcd = 1.552 g cm-3, reflections collected
3
˚
salt (Ir4b-PF6 and Rh4b-PF6, respectively), adopted R absolute
configurations from X-ray analysis, and those of Ir4a and Rh4a
41 443, independent reflections 9654, Rint = 0.043, R1 = 0.0454 (I > 2s(I)),
wR2 = 0.1062 (all data), GOF = 1.021, Flack parameter = 0.00(2).
4826 | Dalton Trans., 2011, 40, 4826–4829
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Fig. 2 CD Spectra of complexes. Left: Ir4a (dashed line) and Ir4b (solid
line) in H2O. Right: Rh4a (dashed line) and Rh4b (solid line) in CH2Cl2.
Each sample was a crude diastereomeric mixture with the 9 : 1 ratio of the
major and minor diastereomers.
the NMR measurements, show that diastereoselective synthesis is
possible because of the steric repulsion between the uncoordinated
glucopyranosyl units during the carbene transfer reaction. a-
and b-Anomeric isomerism of the glucopyranosyl units incor-
porated into the NHC ligand in concert with the chirality at
the anomeric carbon atom in the glucopyranosyl units control
the diastereoselectivity of the formation of the chiral-at-metal
complexes.
Scheme 1 Syntheses of sugar-coated NHC ligand precursors and their Ir
and Rh complexes.
adopted S configurations, which were deduced by using circular
dichroism (CD) spectroscopy, as mentioned below. Crystals of the
diastereomers of Ir4a and Rh4a suitable for X-ray analysis have
not yet been obtained.
The X-ray structure of R-Ir4b-PF6 is shown in Fig. 1. The
structures of the major diastereomers of the Ir and Rh complexes
are similar to each other, and the absolute configuration around
the metal ions was determined to be R by using the structure
of the chiral D-glucopyranosyl unit as an internal reference and
the Flack parameter.8 1H NMR spectra of both the Ir or Rh
complexes showed one set of signals for the ligands, indicating
that the structure observed in the solid state was maintained in
organic solvents.
In order to determine the steric factors governing the selective
formation of the S and R isomers of the a- and b-complexes,
respectively, the conformations of the glucopyranosyl units in the
1
complexes were examined by using H NMR spectroscopy. In
the 1H NMR spectra of the a-ligand precursor 2aHCl, the 3JH–H
coupling constants of 4 Hz between the 1- and 2-positions of
the glucopyranosyl unit and ~7 Hz between the other positions
are rather small in comparison to that for the typical C1 chair
(3JH–H = 9 Hz) due to distortion in the C1 chair conformation,
whereas in the spectra of the b-ligand precursor 2bHCl, coupling
constants (3JH–H = 9 Hz) consistent with the C1 chair conformation
were observed. The coupling constants for all of the b-complexes
corresponding to the C1 chair conformation of the glucopyranosyl
3
units followed a similar trend. On the other hand, the JH–H
coupling constants corresponding to the major diastereomers of
the a-complexes Ir4a and Rh4a were 10 Hz between the 4- and 5-
positions of the glucopyranosyl unit and ~5 Hz between the other
methyne protons. These coupling constants are consistent with a
skewed form of the glucopyranosyl unit.
When the a-ligand coordinates to the metal ion, the imida-
zolylidene group occupies the axial position causing considerable
steric hindrance between the peracetylated glucopyranosyl group
and the H atom at the 5-position of the imidazolylidene or
the other coordinated ligands around the metal center. The
optimized structure of S-chair-[Ir4a] obtained by DFT calculation
(B3LYP/LanL2DZ (for Ir) and 6-31G(d) (for the others)) shows
that the shortest distance between the methyne proton of the
glucopyranosyl group and the imidazolylidene backbone proton
Fig. 1 Structure of the major diastereomer of Ir4b-PF6 with 50%
probability of thermal ellipsoids. Hydrogen atoms, counter ions, and
solvent molecules were omitted for clarity.
In order to deduce the absolute configuration around the metal
center for the a-complexes, CD spectroscopy was performed. The
diastereomers of Ir4a and Rh4a have yet to be separated. Thus, we
compared the CD spectra of crude mixtures of the diastereomers
of the a- and b-complexes, which contained the major and minor
diastereomers in about a 9 : 1 ratio. Interestingly, the CD spectra of
the a-complexes and the corresponding b-complexes were mirror
images of each other (Fig. 2).
The CD spectra indicate that each major diastereomer of the
a-complexes has the opposite absolute configuration to that of the
R-b-complexes. Thus, the major diastereomers of the a-complexes,
Ir4a and Rh4a, have an S configuration. It should be noted that
the D-glucopyranoside chromophore should not contribute to the
CD around 220–500 nm, since no absorption occurs in this region.
Similar relationships between the CD spectra have been reported
for other chiral-at-metal complexes.4 These results, together with
˚
is about 2.1 A, which is shorter than the sum of the van der Waals
˚
radii (2.4 A) (Table. S2, Fig. S6, ESI†). In order to avoid such
steric repulsion, the a-glucopyranoside group adopts the skewed
conformation in the S-a-complexes (Fig. S1, ESI†).
Usually, substitution reactions, including carbene transfer,
involving piano-stool type complexes proceed through 16e in-
termediates produced by the dissociation of one of the ligands.
The intermediate in the initial carbene-transfer process of the
formation reaction, which does not affect the chirality of the
final product, affords a pseudo-tetrahedral monodentate NHC
complex, [MCp*LCl2] (M = Ir, Rh; L = 2a, 2b), similar to those of
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the [IrCp*(NHC)Cl2] complexes. The second step involves chelate
formation of the pyridyl group to the intermediate to produce R
or S chirality at the metal center. The major products were the S-
isomers for the a-complexes and the thermodynamically unstable
R-isomers for the b-complexes. These results show that generation
of the complexes is a kinetically-controlled process. Prochiral
pseudo-tetrahedral or 16-electron pseudo-planar intermediates
should be involved in the isomerization reaction, and the fact
that the reaction of 3b with [MCp*Cl2]2 finished within 5 min,
as mentioned above, means that the high-energy pseudo-planar
transition state is not involved. In this process, the configuration
of the pseudo-tetrahedral intermediate determines the chirality at
the metal center of the final product. There are steric repulsions
between the Cp* ligand and the H atom or the acetyl group
located at the 2-position of the glucopyranosyl unit in the
pseudo-tetrahedral intermediate, as shown in Scheme 2. The
configurations of the a-S and b-R intermediates afford the S-
M4a and R-M4b (M = Ir or Rh) complexes, respectively, via the
dissociation of the chloro ligand and coordination of the pyridyl
group.
In order to gain further information about the isomerization of
R-Ir4b and R-Rh4b, DFT calculations at the B3LYP/LanL2DZ
(for Ir)/6-31G(d) (for others) level were performed on R-[Ir4b]+,
which was crystallographically characterized, and its diastereomer
S-[Ir4b]+ and on the diastereomers of the Ir a-complexes R-[Ir4a]+
and S-[Ir4a]+ with chair and skewed conformations (Table S2,
ESI†). The skewed conformation of the glucopyranosyl unit with
an S configuration at the metal center was determined to be the
most stable for the a-complex, whereas the chair conformation
with an S configuration was the most stable for the b-complex.
The results of the calculations are consistent with the experimental
results that the S-a-complex does not isomerize and that the R-
b-complex isomerizes to the S diastereomer. In addition, it was
found that the R-b-complex was the kinetically favored product.
Chiral-at-metal Ir(III) and Rh(III) complexes were diastereose-
lectively synthesized using chelate-type NHC ligands with a- or b-
glucopyranosyl units. To the best of our knowledge, this is the first
example of the diastereoselective syntheses induced by anomers of
sugar units incorporated into the ligands of metal complexes. The
configuration of the metal center was affected by the conformation
of the a-glucopyranosyl group, which adopts a skewed form
in the complexes, though it adopts a chair form in the ligand
precursor.
Glucopyranosyl imidazoles can be utilized to synthesize a
variety of precursors of N-heterocyclic carbene ligands having a
glucopyranosyl unit by reaction with primary alkyl halides. Since
steric repulsion between acetyl protecting groups is one of the
factors governing the configuration of the complexes, the use of
other protecting groups will affect the configuration of the metal
complexes. Utilization of the anomeric isomers of sugar groups to
control stereochemistry of metal complexes will be important for
preparing new asymmetric catalysts.
This work was partly supported by a Sasakawa Scientific Re-
search Grant from The Japan Science Society. This work was partly
supported by Grant-in Aid for Scientific Research (No. 22550063)
from the Ministry of Education, Culture, Sports, Science and
Technology of Japan. We would like to thank Professor Brian
K. Breedlove for helpful discussion and suggestions.
Scheme 2 Possible intermediates for diastereoselective formation.
There is another possible reaction pathway in which coordi-
nation of pyridine occurs first and subsequent carbene transfer
reaction afforded half sandwich complexes. However, in this route,
the chiral sugar moiety is too far from the metal center to lead to
diastereoselective formation of the complexes.
Notes and references
The a-complexes did not isomerize in solution, such as CHCl3,
CH2Cl2, CH3CN, DMSO, and H2O confirmed by H NMR and
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