Looking inside the intramolecular C-H⋯O hydrogen bond in lactams derived from α-methylbenzylamine

Abstract

Recently, strong evidence that supports the presence of an intramolecular C-H⋯O hydrogen bond in amides derived from the chiral auxiliary α-methylbenzylamine was disclosed. Due to the high importance of this chiral auxiliary in asymmetric synthesis, the inadvertent presence of this C-H⋯O interaction may lead to new interpretations upon stereochemical models in which this chiral auxiliary is present. Therefore, a series of lactams containing the chiral auxiliary α-methylbenzylamine (from three to eight-membered ring) were theoretically studied at the MP2/cc-pVDZ level of theory with the purpose of studying the origin and nature of the C-Hα⋯O interaction. NBO analysis revealed that rehybridization at C atom of the C-Hα bond (s-character at C is 23%) and the subsequent bond polarization are the dominant effect over the orbital interaction energy n(O) →σ∗C-Hα (E(2) < 2 kcal/mol), causing an important shortening of the C-Hα bond distance and an increment in the positive charge in the Hα atom.