Effect of 2,6-Disubstituted Aryl Groups on Acyclic Conformation: Preference for an Antiperiplanar Orientation of the Geminal and Vicinal Hydrogens

Multiple X-ray crystallographic and 1H NMR spectroscopic studies demonstrate that 2,6-disubstituted
aryl groups exert a strong effect on acyclic conformation, inducing the geminal and vicinal hydrogens on
the adjacent sp3−sp3 C−C bond to adopt an antiperiplanar orientation. Twenty-one examples comprising
nitrile, ketone, and dithiane aldols are provided. A search of the Cambridge Structural Database uncovered
an additional 11 examples of this effect. This preference causes some unanticipated remote effects on
acyclic conformations:  in anti-nitrile aldols, this effect causes 2,6-disubstituted aryls to generally prefer
a gauche, rather than antiperiplanar, relationship to the largest vicinal groups. X-ray crystallography,
1H−1H NOESY spectroscopy, and computation demonstrate that minimization of allylic 1,3-strain and
syn-pentane-like interactions work together in establishing this conformational preference.