A new chiral shift reagent for the determination of enantiomeric excess and absolute configuration in cyanohydrins

Abstract

Optically active mandelic acid in the presence of dimethylaminopyridine is an excellent chiral shift reagent for the determination of enantiomeric excess and absolute configuration in cyanohydrins.

Assignment of absolute configuration using chiral reagents and NMR spectroscopy

“…For trisubstituted derivatives such as 65, the relative change in chemical shift of the epoxide hydrogen resonance correlates with the absolute configuration. 136 Similarly, the perturbations in chemical shifts of the Hx and Hy resonances of epoxides (66) and arene oxides with Eu(tfc) 3 and Eu(hfc) 3 are consistent with absolute configuration. 137 The epoxide 1 H signals of chalcone derivatives such as 67 with Eu(hfc) 3 exhibit trends that correlate with absolute configuration as well.…”

Investigation of Lewis Acid versus Lewis Base Catalysis in Asymmetric Cyanohydrin Synthesis

“… [a] Determined by 1 H NMR analysis of the reaction mixture. [b] Determined by 1 H NMR spectroscopy in the presence of ( R )‐mandelic acid and DMAP 26…”

“…Therefore, the enantiomeric excess of the cyanohydrin derived from 3,4-dimethylbenzaldehyde was determined by 1 H NMR analysis [23] of the free cyanohydrin obtained by hydrolysis of the acetate, [25] in the presence of (R)mandelic acid and DMAP. [26] The cyanohydrin derivative ob-tained from 4-methoxybenzaldehyde was found to racemise on hydrolysis, so the enantiomeric purity was determined by comparison of the specific rotation of the trimethylsilyl ether with literature data. [26] In each case, the S enantiomer of the cyanohydrin derivative was obtained from complex 3 derived from (R,R)-diaminocyclohexane, which is consistent with previous work.…”

Applying Biocatalysis to the Synthesis of Diastereomerically Enriched Cyanohydrin Mannosides

“…The absolute configurations of the unreacted cyanohydrin diastereomers D ‐ and L ‐ 3 were determined by the NMR method developed by Moon et al using ( R )‐ and ( S )‐mandelic acids (in separate samples) in the presence of 4‐(dimethylamino)pyridine (DMAP) as chiral shift reagent 13. In the complex with ( R )‐mandelate the α‐proton signal of both D ‐ and L ‐ 3 experiences a larger downfield shift than that of the complex with ( S )‐mandelate [Δ δ RS = +0.066 for D ‐ 3 (a) and +0.063 for L ‐ 3 (b), Figure 1].…”