Synthesis and dynamics of atropisomeric ( S)- N-(α-phenylethyl)benzamides

The synthesis of atropisomeric 2-substituted benzamides 2a– e, 3a– e, and 4a– e, and characterization by X-ray structure analysis of 2d, 2e, 3c, 3e, 4c, and 4e are reported. Dynamic 1H NMR spectroscopic studies of benzamides 2b– d, 3b– d, and 4b– d indicate that only two of the four possible rotamer...

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Bibliographic Details
Published in:Tetrahedron 2007-12, Vol.63 (51), p.12655-12664
Main Authors: Huelgas, Gabriela, Bernès, Sylvain, Sánchez, Mario, Quintero, Leticia, Juaristi, Eusebio, Anaya de Parrodi, Cecilia, Walsh, Patrick J.
Format: Article
Language:English
Subjects:
Atropisomers
Chiral ligands
Semiempirical theoretical calculations
Variable temperature NMR
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Summary:The synthesis of atropisomeric 2-substituted benzamides 2a– e, 3a– e, and 4a– e, and characterization by X-ray structure analysis of 2d, 2e, 3c, 3e, 4c, and 4e are reported. Dynamic 1H NMR spectroscopic studies of benzamides 2b– d, 3b– d, and 4b– d indicate that only two of the four possible rotamers are present in solution, with population ratios ranging between 1.5:1 and 4.1:1. The measured free energy of activation to interconversion of the rotamers ranged from 12.4 to 18.9 kcal mol −1. Benzamides ArCON[( S)-phenethyl] 2 ( 2e, 3e, and 4e), exhibited atropisomer ratios between 1.7:1 and 1:1, and free energies of interconversion of the rotamers ranged from 11.5 to 17.6 kcal mol −1. The highest rotation barriers were observed for the ortho-nitro derivatives 2a– e. Molecular calculations at the semiempirical level (PM3MM) gave free energies of activation for benzamides 2e and 3e of 23.6 and 12.4 kcal mol −1, respectively, which are comparable to the experimental values. [Display omitted]
ISSN:0040-4020
1464-5416
DOI:10.1016/j.tet.2007.10.010