In Situ Assembly of Octahedral Fe(II) Complexes for the Enantiomeric Excess Determination of Chiral Amines Using Circular Dichroism Spectroscopy

Abstract

A method for discriminating between α-chiral primary amine enantiomers is reported. The method utilizes circular dichroism spectroscopy and a sensing ensemble composed of 2-formyl-3-hydroxyl pyridine (4) and Fe(II)(TfO)2. Aldehyde 4 reacts rapidly with chiral amines to form chiral imines, which complex Fe(II) to form a series of diastereomeric octahedral complexes that are CD active in both the UV and visible spectrum. NMR studies showed that, for enantiomerically pure imine complexes, the Δ-fac isomer is preferred. A statistical analysis of the distribution of stereoisomers accurately models the calibration curves for enantiomeric excess. CD signals appearing in the UV region were bisignate, and the null of the CD signals were coincident with maxima in the UV spectrum, consistent with exciton coupling. TTDFT and semi-empirical calculations confirmed that the CD signals in the UV region arise from coupling of the π-π* transitions in the imine chromophores, and can be used to accurately describe the sign and magnitudes of the curves. The CD signals in the visible region arise from metal-to-ligand charge transfer bands, and these signals can be used to determine the ee values of chiral amines with an average absolute error of ±5%. Overall, the strategy presented herein represents a facile in situ assembly that uses commercially available simple reagents to create large optical signals indicative of ee values.

Lanthanide Tris(β‐diketonates) as Useful Probes for Chirality Determination of Biological Amino Alcohols in Vibrational Circular Dichroism: Ligand to Ligand Chirality Transfer in Lanthanide Coordination Sphere

“…Electronic circular dichroism (ECD) is a complementary method by virtue of its applicability to the targeted molecules in both solution and solid states . In addition to the normal direct measurements, a variety of achiral and chromophoric probes enable versatile chirality determinations of nonchromophoric substrates . Berova et al developed dimeric metalloporphyrin host systems which incorporate chiral substrates between two porphyrin rings to show characteristic ECD signals as exciton‐coupled ECD in the porphyrin spectral region .…”

Rhodium‐Catalyzed Asymmetric Hydrogenation of Unprotected NH Imines Assisted by a Thiourea

“…[17] Although the accuracy is not ideal (an average absolute error of 9%), [14] it is much faster and being transitioned to aid in our research.…”

Well plate circular dichroism reader for the rapid determination of enantiomeric excess

“…35 Aldehyde 1 reacts with the a chiral amine ( 4 - 7 ) to give a bidentate imine 2 . Fe(II), in turn, binds three equivalents of that imine to give several helical octahedral complexes represented as 3 , whose handedness is dictated by the chirality of the amine (Scheme 1).…”

“…We determined the enantioenrichment of amine 4 - 7 by measuring CD in the strong metal-to-ligand charge transfer bands that arise upon formation of complex 3 . 35 This reaction is fast, simple, relies on commercially available reagents and can be analyzed in situ .…”

“…29 For example, the groups of Anslyn and Wolf have developed and tested CD methods for the analysis of chiral analytes including amino acids 30 , alcohols, 31 amino alcohols 32,33 carboxylates 34 and amines. 35-38 Biological/biochemical sciences may benefit likewise. CD spectroscopy is sensitive to the conformational analysis of peptides, proteins, and nucleic acids.…”