Fig. 5: Computational studies by DFT reveal attributes of transition states and the Meisenheimer intermediate. | Nature Communications

Fig. 5: Computational studies by DFT reveal attributes of transition states and the Meisenheimer intermediate.

From: Nucleophilic aromatic substitutions enable diversity-oriented synthesis of heterocyclic atropisomers via non-atropisomeric intermediates

Fig. 5

The calculations support a stepwise mechanism in which the addition step is rate-determining (or turnover-limiting in the catalytic reactions) but it is not the atropisomer-forming step. This attribute is supported by the calculated energy barrier to rotation around the C–N bond in the Meisenheimer intermediate, which is 16.6 kcal/mol, therefore lower than the atropisomerism threshold (21 kcal/mol at room temperature) and less than half of that of the product (35.2 kcal/mol; see Supplementary Section 6,12, and 14 for mechanistic details). TS transition state; (X.X) = relative free energies in kcal/mol; DFT density functional theory, DFT method: PBE0-D3/def2-TZVP level in DMSO with CPCM solvation model.

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