Detection of the Heterochirality of a 1:2 Metal/Ph-pybox Complex Ion by ESIMS

Abstract

The heterochirality of a 1:2 metal/Ph-pybox complex ion was encyclopedically evaluated by ESIMS using pseudoracemic (R,R)-and (S,S)-Ph-pybox pair, which were unlabeled/labeled by deuterium atoms, respectively. The heterochiral complex was predominantly formed in all investigated 1:2 metal/Ph-pybox complex ions.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.26 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. 3,4 Williams has reported that heterochiral [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 diastereoselectivity 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 Pr i -pybox was dependent on the Ln 3+ radius: Eu(OTf) 3 gave exclusively the heterochiral complexes [Eu(OTf) , whereas the use of Yb(OTf) 3 produces an exclusively racemic mixture of homochiral complexes6 Although 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).Isotopic-labeling is a highly useful method for the discrimination 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 complexes. 1S-d was synthesized from pyridine-2,6-dicarbonyl chloride and (S)-phenylglycinol-d 2 , which was obtained from the (S)-phenylglycine methyl ester by reduction using NaBD 4 in THF.7,10 The deuteration rate of 71% was determined by comparing the isotopic pattern with the theoretical pattern ( Figure S1). 10The sample was prepared by mixing 1R, 1S-d, and metal nitrate at concentrations of 10, 10, and 20¯M in 10% methanol...

Spin States of Homochiral and Heterochiral Isomers of [Fe(PyBox)2]2+ Derivatives

“…For comparison, a freshly prepared 1:1:1 mixture of ( R )‐ L Ph , ( S )‐ L Ph and iron(II) salt does contain both diastereomers. That is consistent with a previous report that {Fe(( R )‐ L Ph )[( S )‐ L Ph ]} 2+ exists as a single isomer with a diastereomeric excess of 0.95, as measured by mass spectrometry …”

“…The optical purity of ( R )‐ versus ( RS )‐[M( L Ph ) 2 ] 2+ derivatives in solution has been investigated before, but ( R )‐ versus ( RS )‐[M( L i Pr ) 2 ] 2+ has not. It was unexpected that ( RS )‐ 4 undergoes significant racemization through ligand redistribution in solution (Figure ), whereas ( RS )‐ 3 does not (Figure ).…”

The speciation of homochiral and heterochiral diastereomers of homoleptic cobalt(II) and zinc(II) PyBox complexes

“…Previous 1 H NMR studies have shown that (RS)-[M(L Ph ) 2 ] 2+ (M = Fe, Co or Zn) are stable in solution, and don't undergo racemisation by ligand redistribution [6,10,12]. This was also confirmed in the gas phase, by mass spectrometry [9]. Comparison of the 1 H NMR spectra of (RS)-1 and (RS)-3 with their homochiral congeners confirms that conclusion (Figure 4 and Supporting Information) Figure . There is no evidence for partial decoordination of L Ph in the spectra of the zinc complexes, as was observed for the triflate salt of (R)-1 under some conditions [12].…”

“…<Insert Scheme 1 here> That study was possible, because heterochiral [Fe((R)-L Ph )((S)-L Ph )][ClO 4 ] 2 is stable in solution, and does not undergo detectable racemisation through ligand redistribution [9]. The same is true for salts of the analogous complexes [M((R)-L Ph )((S)-L Ph )] 2+ (M = Co [10,11], Zn [12], Cu [13] or another metal ion [9]).…”

“…<Insert Scheme 1 here> That study was possible, because heterochiral [Fe((R)-L Ph )((S)-L Ph )][ClO 4 ] 2 is stable in solution, and does not undergo detectable racemisation through ligand redistribution [9]. The same is true for salts of the analogous complexes [M((R)-L Ph )((S)-L Ph )] 2+ (M = Co [10,11], Zn [12], Cu [13] or another metal ion [9]). However, in contrast, heterochiral [Fe((R)-L iPr )((S)-L iPr )][ClO 4 ] 2 [6], and [Co((R)-L R )((S)-L R )] 2+ (R = Me or Bn) [10], do undergo partial racemisation under the same conditions.…”