(+)-BINOL and Pure Shift Experiment: A Bidirectional Approach for NMR Chiral Discrimination of Overcrowded Spectra of Primary Amines

Abstract

In this work, enantiopure 1,1'-bi-2-naphthol (BINOL) derivatives and carboxylic acids were evaluated as chiral solvating agents (CSAs) in the nuclear magnetic resonance (NMR) chiral discrimination of primary amines. Among the CSAs screened, the readily available (+)-BINOL revealed a simple and rapid chiral auxiliary for 1 H NMR chiral discrimination. The procedure required few minutes, assigning of the absolute configuration. The protocol was improved using the 1 H pure shift pulse sequence for overcrowded alkyl primary amines due to the absence of J HH couplings. The 1 H pure shift NMR experiment and the readily available (+)-BINOL chiral auxiliary can be used for routine chiral discrimination analysis of complex NMR spectra.

NMR chiral recognition of lipoic acid by cinchonidine CSA: A stereocenter beyond the organic function

“…Finally, we carried out the chiral discrimination using the pure shift NMR experiment, a newer pulse sequence that eliminates all multiplicity, producing a clear visualization of the diastereotopic signals, once all proton signals are singlets (Figure 3; black spectrum, E = 0.05/0.01 = 5.0). This last pulse sequence is not a trivial task to be implemented in the NMR console; however, it can be an effective methodology for overcrowded NMR spectra 38 …”

A simple protocol for determination of enantiopurity of amines using BINOL derivatives as chiral solvating agentsvia1H- and19F-NMR spectroscopic analysis

“…37–39 Among all the chiral auxiliaries reported for NMR chiral recognition, BINOL and its derivatives represent a useful auxiliary because of their direct utilization as a CSA. The BINOL and its derivatives are reported as a chiral solvating agent for NMR enantiodifferentiation of amines, 26 promethazine, 27 alkaloid crispine A, 28 isoflavones, 40 sulfinimines, 41 omeprazole, 42 and flavones. 43…”

“…The determination of enantiopurity via NMR spectroscopy required the presence of a chiral auxiliary to convert the enantiomers into diastereomers. The most commonly used chiral auxiliaries are chiral solvating agents {CSAs like tyrosine-modied pillar [5] arenes, R-VAPOL-phosphoric acid, organic-soluble acids, benzene tricarboxamide-based hydrogelators, BINOL phosphoric acid, Kagan's amides, roof-shape amines, BINOL and its derivatives}, [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] chiral derivatizing agents {CDAs like D-[Ir(ppy) 2 (MeCN) 2 ](PF 6 ) (ppy is 2-phenylpyridine), a-methoxy-aphenylacetic acid (MPA), a-methoxy-a-triuoromethylphenylacetic acid (MTPA) and BINOL}, [31][32][33][34][35][36] chiral lanthanide shi reagents {CLSRs like [Eu(tfc) 3 ], [Eu(hfc) 3 ], [Sm(tfc) 3 ], and [(R)-Pr(tfc) 3 ]}. [37][38][39] Among all the chiral auxiliaries reported for NMR chiral recognition, BINOL and its derivatives represent a useful auxiliary because of their direct utilization as a CSA.…”

“…[37][38][39] Among all the chiral auxiliaries reported for NMR chiral recognition, BINOL and its derivatives represent a useful auxiliary because of their direct utilization as a CSA. The BINOL and its derivatives are reported as a chiral solvating agent for NMR enantiodifferentiation of amines, 26 promethazine, 27 alkaloid crispine A, 28 isoavones, 40 sulnimines, 41 omeprazole, 42 and avones. 43 The nature of solvent is also important for this type of chiral analysis because the anisochrony observed between diastereomeric host-guest complexes is preeminent in nonpolar deuterated solvents like CCl 4 , CDCl 3 , and C 6 D 6 .…”

A Gallium-based Chiral Solvating Agent Enables the Use of 1H NMR Spectroscopy to Differentiate Chiral Alcohols

“…This useful technique was successfully demonstrated for a variety of substrates with chiral amines and carboxylic acids being the most commonly targeted substrates (Benedict et al., 2018, Chen et al., 2018, Ema et al., 2018, Khanvilkar and Bedekar, 2018, Merino et al., 2018, Liu et al., 2011, Chinchilla et al., 1995). The emphasis on these species is not surprising, because the majority of chiral solvating agents employ non-covalent interactions such as hydrogen bonds and electrostatic attractions for structural recognition (Benedict et al., 2018, Chen et al., 2018, Ema et al., 2018, Khanvilkar and Bedekar, 2018, Merino et al., 2018, Liu et al., 2011, Chinchilla et al., 1995). Substrates that form relatively weak hydrogen bonds and are less strongly coordinating such as alcohols are more challenging to study.…”