Dynamic Covalent Optical Chirality Sensing with a Sterically Encumbered Aminoborane

Abstract

A sterically encumbered aminoborane sensor is introduced and used for quantitative stereochemical analysis of monoalcohols, diols and amino alcohols. The small‐molecule probe exhibits a rigid ortho‐substituted arene scaffold with a proximate boron binding site and a triarylamine circular dichroism (CD) reporter unit which proved to be crucial for the observed chiroptical signal induction. Coordination of the chiral target molecule produces strong Cotton effects and UV changes that are readily correlated to its absolute configuration, enantiomeric composition and concentration to achieve comprehensive stereochemical analysis within a 5 % absolute error margin. The sensing method was successfully applied in the chromatography‐free analysis of less than one milligram of a crude asymmetric reaction mixture and the advantages of this chiroptical sensing approach, which is amenable to high‐throughput experimentation equipment and automation, over traditional methods is discussed.

Circular Dichroism Sensing: Strategies and Applications

“…Modern high-throughput experimentation (HTE) equipment makes this an easy task, but the bottleneck is the reaction analysis which generally entails tedious product purification steps and subsequent chromatographic ee determination by processing one reaction at a time. Anslyn, [162][163][164][165][166] Arai, [167,168] Biedermann, [44] Jiang, [46,47] Joyce, [169] Wolf [65,131,161,[170][171][172] and others have demonstrated how chiroptical sensing can resolve this analytical holdup, often by directly applying crude asymmetric reaction mixtures into their assays. [173] In one of the early examples of asymmetric reaction analysis, the Brønsted/Lewis acid 98 was applied to the chlorodiisopinocampheylborane mediated reduction of phenylglyoxlic acid, 99, to mandelic acid, 100.…”

“…Because the sign of the generated CD curves is causally linked to the chirality of the analyte it reveals its absolute configuration. Quantitative ee analysis is also possible and has been demonstrated numerous times with a very broad range of chiral compounds by Anslyn, [34][35][36][37][38][39][40][41][42][43] Nau and Biedermann, [44,45] Jiang, [46][47][48][49] Zonta, [50][51][52][53][54][55] Wolf [56][57][58][59][60][61][62][63][64][65] and through collaborative efforts from Chin, Hong and Kim [66][67][68] as well as Baik, Yoon and Kim. [69] These and several other laboratories [70][71][72][73][74][75][76] have developed assays that make use of the intensity of the induced CD amplitudes which is readily correlated to the ee of the analyte with the help of a calibration curve.…”

Dynamic Covalent Reactions and Chirality Sensing with Diphenylethene Derived Hemiaminals

“…Through the formation of boronic ester or phosphite, circular dichroism probes based on acridine [16] and chlorophosphite [17] motif were developed for monoalcohols sensing. Recently a sterically encumbered aminoborane optical sensor was employed for quantitative stereochemical analysis of monoalcohols, diols, and amino alcohols [18] …”

“…Recently a sterically encumbered aminoborane optical sensor was employed for quantitative stereochemical analysis of monoalcohols, diols, and amino alcohols. [18] In 2018, our group reported a versatile chirality sensing system for monoalcohols and monoamines based on a combination of DCC and axial chirality of biphenyl scaffolds (Figure 1a). [19] Diphenylethene (DPE) is a part of the classical aggregation-induced emission molecule tetraphenylethylene, [20] and the helical chirality arising from its propeller configuration offers a diverse platform for the regulation of chirality.…”