In non-polar solvents, chiral europium complexes provide attractive n. m. r. shift reagents to resolve spectra of optically active cations, and, in particular, for tris(phenanthroline)ruthenium dichloride,^1H n. m. r. shift differences of up to 0.7 p.p.m. between isomers easily permit the determination of absolute enantiomeric purity

Barton, Jacqueline K.

Nowick, James S.

English

Jacqueline K. Barton

James S. Nowick

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Application of chiral lanthanide-induced shift reagents to optically active cations: the use of tris[3-(trifluoromethylhydroxymethylene)-(+)-camphorato]europium(III) to determine the enantiomeric purity of tris(phenanthroline)ruthenium(II) dichloride

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1650 J. CHEM. SOC., CHEM. COMMUN., I 984 
Application of Chiral Lanthanide-induced Shift Reagents to Optically Active Cations: 
the Use of Tris[3-(trifluoromethylhydroxymethylene)-( + )-camphorato]europium(m) to 
Determine the Enantiomeric Purity of Tris(phenanthroline)ruthenium(n) Dichloride 
Jacqueline K. Barton* and James S. Nowick 
Department of Chemistry, Columbia University, New York, NY 10027, U.S.A. 
In non-polar solvents, chiral europium complexes provide attractive n.m.r. shift reagents to resolve spectra of 
optically active cations, and, in particular, for tris(phenanthroline)ruthenium dichloride, 1H n.m.r. shift differences of 
up to 0.7 p.p.m. between isomers easily permit the determination of absolute enantiomeric purity. 
There has been considerable interest in the determination of 
enantiomeric purity by n.m.r. spectroscopy using chiral shift 
reagents. 1- 4 Although lanthanide-induced shift reagents were 
first used to study cations in 1973,5 chirallanthanide-induced 
shift reagents have been used only with neutral species. We 
report the application of chiral lanthanide-induced shift 
reagents to optically active cations. For the following study we 
employed tris(phenanthroline )ruthenium(n) complexes, 
[Ru(phen)3)2+, which we are currently using as chiral probes 
for DNA.6 
Tris(phenanthroline )ruthenium( n) dichloride was prepared 
as described by Lin et al. 7 and partially resolved by recrystalli-
J. CHEM. SOC., CHEM. COMMUN., 1984 1651 
Table 1. The effect of Eu(tfc):, upon the 1 H n.m.r. spectrum of [Ru(phenh]Cl2 ·xH20 in CD 2Cl 2 . 
Without Eu(tfch With Eu(tfc), 
b,p.p.m. ~b. p.p.m. ~~<'l,p.p.m. 
~ A ~ A Proton 
Ha 
Hh 
He 
Hct 
b,p.p.m. 
8.582 
7.815 
8.255 
8.215 
15.833 16.565 7.251 7.983 0.732 
~ 0.08a 
0.185 
0.225 
16.24Qa 
12.609 12.794 4.354 4.539 
11.573 11.798 3.358 3.583 
a The ~- and A-Hh quadruplets are overlapping. Values of (l and ~b are given for the centre of the Hh cluster of peaks. 
Differentiation between Hh protons has been evident in some experiments. 
zation with antimony o-tartrate anion;i1 treatment of the 
tartrate with perchloric acid, sodium perchlorate, or sodium 
chloride yielded optically enriched perchlorate, [Ru-
(phen)3](Cl04h·xH20, or chloride, [Ru(phen):,]Cl2·xH20. 
We first attempted to observe chiral shifts of the perchlorate 
and chloride in (CD3)2SO, and of the perchlorate in CD2Cl2, 
in the presence of tris-[3-( trifluoromethylhydroxymethylene )-
( + )-camphorato)europium(m), Eu(tfc)3 . In each case, only 
small changes in chemical shift ( < 0.15 p. p.m.) were seen, and 
no differentiation between enantiomers was observed. 
These results are not surprising in view of the general model 
for lanthanide-induced shifts of cations: the anion is co-
ordinated by the lanthanide shift reagent and the cation forms 
an outer-sphere complex (ion pair) with the co-ordinated 
anion. 5 We find that the nature of the anion as well as the 
nature of the solvent is critical to the degree of induced shift 
observed. Small, highly charged anions favour co-ordination 
and allow the cation to approach the shift reagent more 
closely, yielding greater induced shifts. The use of a small 
anion may also enhance steric interactions between the cation 
and shift reagent. In addition the concentration of the ion 
pair-shift reagent complex is maximized in non-polar or 
slightly polar solvents. More polar solvents containing an 
atom which can co-ordinate to the shift reagent, thus 
competing with the anion, or which would independently 
solvate the ions and shift reagent, yield very small lanthanide-
induced shifts. (Non-polar solvents, however, limit the 
solubility of ionic substrate, thus requiring a large number of 
pulses for a good signal-to-noise ratio.) 
With these considerations in mind, we next examined the 
smaller chloride complex in CD2Cl2. From the 1H n.m.r. 
spectrum of [Ru(phen)3)C12·xH20 (0.55 ml; 1. 9 x 10-3 M) 
containing Eu(tfc)3 (2.7 x 10-2M) in CD2Cl2, we were able to 
distinguish between the two enantiomers and determine the 
enantiomeric purity of the sample. t The resulting spectrum at 
200 MHz is shown in Figure 1(a) and is compared to that of the 
same solution in the absence of Eu(tfc)3 in Figure l(b). 
Observed chemical shifts (b), downfield shifts induced by 
the lanthanide reagent (~b), and the magnitudes of the 
difference in chemical shifts of analogous protons of the two 
enantiomers upon addition of shift reagent (~~b), are 
summarized in Table 1. As is shown in Table 1, very large 
lanthanide-induced shifts (~b) were observed, and substantial 
t Solutions of [Ru(phen)JCI2 ·xH20 were prepared by stirring an 
excess of the compound in CD2Cl2 and filtering. Eu(tfch (13.2 mg) 
was then added and the resulting solution filtered through glass wool. 
Ruthenium concentrations were determined spectrophotometrically 
by dilution. Spectra were taken using a Varian XL-200 n.m.r. 
spectrometer with SiMe4 as internal standard. Assignments of peaks 
were made in accordance with the literature (E. C. Constable and J. 
Lewis, Inorg. Chim. Acta, 1983,70, 251) on the basis of peak position 
and coupling constants in CD3COCD-,. 
2+ 
A 
Hd 
He 
Hd Ha ~ Hb 
Ha 
Hb 
16 14 12 10 8 
o,p.p.m. 
Figure 1. The 1H n.m.r. spectrum of ~-enriched [Ru(phcn),-
Cl2]·xH20 in the presence (a) and absence (h) of Eu(tfch Note the 
large difference in chemical shift between H", He, and H" of the ~­
and A- enantiomers in the presence of Eu(tfc)3 . The broad peak. 
denoted x in spectrum (a), is associated with the shift reagent. 
differences between analogous Ha, Hh, and He protons of the 
two enantiomers were found. It is also noteworthy that despite 
the high concentration of shift reagent, excessive line 
broadening is not evident [ ~v (Hd) = 3 and 2 Hz in the 
presence and absence of Eu(tfch respectively]. Experiments 
with lower ratios of shift reagent to substrate (1: 2) yielded 
smaller induced shifts (0.2-0.5 p.p.m.) and enantiomeric 
1652 
shift differences (0.02-0.07 p.p.m.) with less line 
broadening. 
The db of Ha and Hh and smaller db of He and Hd are 
consistent with an ion-pairing model for the lanthanide-
induced shifts. The Ru(phen):;2+ and Eu(tfch species may sit 
on the chloride anion with the c~ axes intersecting this anion, 
thus placing and Hr. in region of greater induced shifting. 
The fact that and Hh have similar db values but very 
different ddb suggests that there are significant conforma-
tional differences between the diastereisomeric d-Ru-
(phen):;2+-CI--Eu(tfch and i\-Ru(phen)32+-CI--Eu(tfc)_, 
complexes. It is interesting that specific donor-acceptor 
interactions between functional groups on the shift reagent 
and chiral complex are not necessary to obtain these distinct 
diastereoisomeric complexes.:j: 
Comparison of the areas of the well resolved Hd protons of 
the two enantiomers permitted calculation of the enan-
tiomeric purity of the sample; the value obtained by this 
method supported that determined by polarimetry .'1 
In summary, by n.m.r. spectroscopy with chiral shift 
reagents we have observed differences in chemical shift 
between enantiomers of a cationic species, Ru(phenh2+, and 
have used this technique to determine enantiomeric purity. 
This direct method of determination of enantiomeric purity is 
more desirable than polarimetry since polarimetry requires an 
optically pure reference sample yet fails to guarantee that the 
reference sample is optically pure. We believe this work to be 
:j: Differential chiral induced shifts have also been obtained with 
[(4.7-Ph2phenbRu]C12 and Eu(tfc)J. With a diamagnetic chiral 
soi·vatm£ agent, it is unlikely that such dramatic shift differences 
would observed between optically active cations, even with high 
diastereoisomeric discrimination. 
L CHEM. SOC., CHEM. COMMUN .. 1984 
the first to report the application of chiral shift reagents to 
cations and expect that this technique may be generally useful. 
This work was supported by a grant from the National 
Institutes of Health. J. K. B. is a Research Fe\\ow of the 
Alfred P. Sloan Foundation. We thank Jonathan M. Goldberg 
and Elias Lolis for providing samples of Ru(phen):,2+ salts. 
Received, 16th August 1984; Com. 1188 
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Application of Chiral Lanthanide-induced Shift Reagents to Optically Active Cations: the Use of Tris[3-(trifluoromethylhydroxymethylene)-( + )-camphorato]europium(III) to Determine the Enantiomeric Purity of Tris(phenanthroline)ruthenium(II) Dichloride

l&quot;l.atJ'&quot;'&quot;&quot;'· ibid.,

Soc., Dalton Trans ..

http://authors.library.caltech.edu/32202/1/BARjcsss84.pdf

Application of Chiral Lanthanide-induced Shift Reagents to Optically Active Cations: the Use of Tris[3-(trifluoromethylhydroxymethylene)-( + )-camphorato]europium(III) to Determine the Enantiomeric Purity of Tris(phenanthroline)ruthenium(II) Dichloride

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