Chiral sulfinamides have found widespread use in synthesis as chiral auxiliaries, ligands, and asymmetric building blocks. As their enantioselective synthesis is usually achieved using kinetic resolution processes, an effective method for determining their enantiomeric excess (ee) is crucial. The Bull and James groups have previously reported the development of chiral three-component derivatization protocols for determining the ee of chiral primary amines, diamines, and hydroxylamines using 1H NMR spectroscopic analysis. These protocols involve derivatization of a chiral analyte with 2-formylphenylboronic acid and an enantiopure diol, to afford a mixture of diastereomeric iminoboronate ester complexes that exhibit well resolved 1H NMR spectra. The resultant diastereomeric ratio (dr) of these complexes may then be determined by integration of characteristic resonances in their 1H NMR spectra. Since no kinetic resolution occurs in the derivatisation process, the measured dr is an accurate reflection of the ee of the parent chiral analyte. We now report that a three-component derivatization protocol employing 2-formylphenylboronic acid and pinanediol can also be used to determine the enantiopurity of chiral sulfinamides. This protocol affords mixtures of sulfiniminoboronate esters, whose dr’s can be determined by integration of the corresponding sulfinimine proton resonances. We also report that this derivatisation methodology can be used for the chiral resolution of sulfinamides on a preparative scale, with this type of iminoboronate ester complexes being sufficiently stable to enable their separation by chromatography. Subsequent acid hydrolysis of the resultant diastereomerically pure sulfiniminoboronate diastereomers can then be carried out to afford both enantiomers of the chiral sulfinamide.

Chiral derivatization of sulfinamides for 1H NMR enantiomeric excess determination and chiral resolution

2019 Fall National Meeting

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