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. 2022 Sep 30;55(20):2892–2903. doi: 10.1021/acs.accounts.2c00479

Table 2. Choosing an Experimental Technique for Configurational Stability Assessment.

Technique Favored by Disfavored when Compound requirement
VT-NMR: Line-shape analysis, EXSY, or kinetic analyses Fast interconversion (t1/2 < 1 s,26 e.g., analysis of nonchromatographically separable isomer mixtures), ΔG < 23 kcal/mol27 Atropisomers are enantiomers or chemically unstable at elevated temperature ∼3 mg of atropisomer mixture (or atropisomerically enriched material)
Time-course NMR Medium-to-slow interconversion within the accessible temperature rage (t1/2 > 5 min23), ΔG = 22–33 kcal/mol28 Atropisomers are enantiomers or unstable, chiral separation is not feasible ∼3 mg of atropisomerically enriched material
Chiral Chromatography (e.g., HPLC, SFC) Slow interconversion (t1/2 > 20 min23), ΔG > 24 kcal/mol Atropisomers are rapidly converting, or chiral separation is not feasible <1 mg of atropisomerically enriched material