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Published on the web May 8, 2010
Detection of the Heterochirality of a 1:2 Metal/Ph-pybox Complex Ion by ESIMS
Hirofumi Sato,*1 Yoshitomo Suzuki,2 Yoshio Takai,3 Hideya Kawasaki,2 Ryuichi Arakawa,2 and Motohiro Shizuma1
1Department of Biochemistry, Osaka Municipal Technical Research Institute,
1-6-50 Morinomiya, Joto-ku, Osaka 536-8553
2Department of Applied Chemistry, Kansai University, Suita, Osaka 564-8680
3Material Analysis Center, The Institute of Scientific and Industrial Research, Osaka University,
Ibaraki, Osaka 567-0047
(Received March 4, 2010; CL-100203; E-mail: hsato@omtri.or.jp)
The heterochirality of a 1:2 metal/Ph-pybox complex ion
was encyclopedically evaluated by ESIMS using pseudo-
racemic (R,R)- and (S,S)-Ph-pybox pair, which were unla-
beled/labeled by deuterium atoms, respectively. The hetero-
chiral complex was predominantly formed in all investigated 1:2
metal/Ph-pybox complex ions.
O
O
O
O
R
R
N
N
N
N
N
N
R
R
Ph
Ph
Ph
Ph
1R
1S (R = H)
1S-d (R = D)
The bis(oxazolinyl)pyridine (Sub-pybox, Sub = substituent)
family of tridentate ligands were first developed by Nishiyama
and co-workers for enantioselective organometallic catalysis,1
and have also been used to generate chiral Lewis acid catalysts
with transition metals and lanthanides.2-6 Selective formation of
crystalline diastereomeric complexes has been observed in the
1:2 metal/Ph-pybox complex ([M(1)2]) as follows. Evans and
Jørgensen have both observed that, even using a M:1 ratio of
1:1, racemic 1 gave the near insoluble, catalytically inactive
Figure 1. Structure of the Ph-pybox showing the labeling with
and without deuterium atoms (1R, 1S, and 1S-d, respectively).
complexes. 1S-d was synthesized from pyridine-2,6-dicarbonyl
chloride and (S)-phenylglycinol-d2, which was obtained from
the (S)-phenylglycine methyl ester by reduction using NaBD4
in THF.7,10 The deuteration rate of 71% was determined by
comparing the isotopic pattern with the theoretical pattern
(Figure S1).10
complex [M(1R)(1S)]2+ 3,4
Williams has reported that hetero-
.
chiral [Co(Sub-pybox)2] was formed selectively when Sub was
Ph; however, mixtures of homo- and heterochiral complexes
were formed when Sub was Me and Bz.5 This diastereoselec-
tivity was explained by the avoidance of steric interference
between Ph-substituents on different ligands in the heterochiral
complex and the possibility of favorable ³-stacking interactions
between the Ph-substituents of one pybox ligand with the
pyridine ring of another pybox ligand. Aspinall found that the
outcome of the reaction of Ln(OTf)3 with 2 equiv of racemic
Pri-pybox was dependent on the Ln3+ radius: Eu(OTf)3 gave
exclusively the heterochiral complexes [Eu(OTf)3(R-Pri-
pybox)(S-Pri-pybox)], whereas the use of Yb(OTf)3 produces
an exclusively racemic mixture of homochiral complexes
[Yb(OTf)2(R-Pri-pybox)2]+ and [Yb(OTf)2(S-Pri-pybox)2]+.6 Al-
though the metal dependency of the 1:2 metal/pybox complex
structure is interesting, previous structural analysis was solely
dependent on crystallographic analysis. Recently, chiral mass
spectrometry has been developed as a new analytical approach
for stereochemistry, which has the advantages of being a rapid
and simple analytical technique.7 Herein, we report the explicit
index of the heterochiral complex selectivity using electro-spray
ionization mass spectrometry (ESIMS).
The sample was prepared by mixing 1R, 1S-d, and metal
nitrate at concentrations of 10, 10, and 20 ¯M in 10% methanol
in acetonitrile, respectively. The mixture was capped and left
undisturbed in a plastic bottle at room temperature for 24 h.
The ESIMS experiments were conducted on a ThermoQuest
LCQDECA with an ion trap instrument. The following instrument
and analytical conditions were used: spray voltage, 5 kV; spray
current, 0.10 ¯A; sheath gas flow rate, 29.2 units (roughly
0.78 L min¹1); capillary voltage, 35.2 V; heated capillary tem-
perature, 200 °C. The experiments were conducted in the
positive ion mode. Spectra shown represent the average of 60
scans, with each scan requiring 0.2 s. The sample was infused
¹1
via a syringe pump at a flow rate of 3 ¯L min
.
Typical mass spectra of Na and La systems are shown in
Figure 2. In the case of the Na system, the highest mass peak at
m/z 765 corresponds to the mass of the heterochiral complex ion
[Na(1R)(1S-d)]+, consisting of sodium and two Ph-pybox
ligands, in which the absolute configuration is different. The
inset to the figure shows the peaks around the RS-heterochiral
complex ion peak (circle). RR- (triangle) and SS-homochiral
(diamond) complex ion peaks were also observed four units
apart from the RS-homochiral complex ion peak. The peak
intensity should reflect the amount of each diastereomer when
the ionization efficiencies are the same. Thus, eq 1 provides the
diastereomeric excess of the heterochiral complex (deRS) in
forming the 1:2 metal/Ph-pybox complex.
Isotopic-labeling is a highly useful method for the discrim-
ination of a compound from the same structural compounds
using mass spectrometry.8 In the present study we used a
pseudo-racemic mixture of (R,R)- and (S,S)-Ph-pybox (1R and
1S-d, respectively) which was unlabeled/labeled with four
deuterium atoms at the 5-position of oxazoline (Figure 1).9 As
the labeled position is located on the outside of the tridentate
nitrogen atoms, the labeling has no influence on the formation of
deRS ¼ ðIRS ꢀ IRR ꢀ ISSÞ=ðIRS þ IRR þ ISS
Þ
ð1Þ
where deRS is the diastereomeric excess of the heterochiral
complex, IRS is the intensity of the RS-heterochiral complex ion
Chem. Lett. 2010, 39, 564-566
© 2010 The Chemical Society of Japan
Sato, Hirofumi
