Undergraduate Laboratory Experiment To Determine Absolute Configuration Using Thin-Layer Chromatography

Abstract

A new undergraduate organic chemistry laboratory experiment has been developed to determine the absolute configuration of enantioenriched secondary alcohols with the competing enantioselective conversion (CEC) method. The CEC method uses both enantiomers of a chiral kinetic resolution reagent in parallel reactions to identify the fast-reacting reagent and thus the configuration of the alcohol. Students working in pairs are given one of three enantioenriched secondary alcohols with an unknown absolute configuration. They assign the molecular structure using the corresponding 1H NMR spectrum and determine the absolute configuration via the CEC method. The parallel reactions are run at room temperature for 1 h using small quantities of solvent, substrate, and catalyst. Students use thin-layer chromatography (TLC) to analyze the parallel reactions and determine the fast reaction qualitatively. The free program ImageJ is used with a picture of the TLC plate to carry out a quantitative analysis of reaction conversion. Data collected in the spring 2013 laboratory course (n = 1036) show that 93.6% of students determined the absolute configuration of their unknown correctly with just a qualitative analysis of the TLC plate. This experiment provides a platform for discussions of stereochemistry, mechanism, kinetics, energy diagrams, and transition states.

Heteroatom-Directed Acylation of Secondary Alcohols To Assign Absolute Configuration

“…There are also examples of cases in which Mosher’s method fails to make an assignment . Our CEC method for secondary alcohols is operationally simple, and has even been incorporated in an undergraduate laboratory experiment . Extending the CEC method to 2°–3°, 1,2-diols would be a useful alternative to these methods, and could teach us about the factors governing selectivity in HBTM-catalyzed acylation reactions.…”

Nanomole-Scale Assignment and One-Use Kits for Determining the Absolute Configuration of Secondary Alcohols

“…The identity of the fast reaction is then compared with an empirical mnemonic in order to assign the absolute configuration of the stereogenic center. The CEC method has been applied to secondary alcohols, oxazolidinones, lactams, thiolactams, and primary amines. − Characterization techniques used to determine the reaction conversion include 1 H NMR spectroscopy, thin-layer chromatography, and electrospray ionization-mass spectrometry (ESI-MS).…”

Determination of the Absolute Configuration of β-Chiral Primary Alcohols Using the Competing Enantioselective Conversion Method

“…The CEC method is much less labor intensive than the Mosher’s derivatization methods, for example, and has proven robust enough to be incorporated into an undergraduate laboratory experiment. 13c The competing enantioselective conversion (CEC) method has been used to determine the configuration of primary amines, 11 lactams, 12 oxazolidinones, 12 and secondary alcohols. 10,13,14…”

“…Previous experience has shown, not unexpectedly, that a sample with lower enantiopurity will reduce the observed difference between the conversions. 13a With the exception of compounds 13 and 21 , all of the samples are ≥89% ee, so the effect will be negligible. Gratifyingly, this CEC method also showed selectivity for scopolamine, 14 , demonstrating its utility for natural products containing this functional group array.…”

“…Birman has developed a number of enantioselective acylating catalysts, including homobenzotetramisole (HBTM) 1 , for kinetic resolutions of secondary alcohols . Our group has previously employed HBTM as a catalyst for CEC methods for secondary alcohols and other functional groups . We sought to determine whether HBTM could be used for a CEC method with β-chiral primary alcohols by first probing its effectiveness in the kinetic resolution of racemic substrates.…”