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.
Highlights
With the vast theoretical and experimental contributions coming from the laboratories of Desiraju [1,2,3], Steiner [4,5], and Scheiner [6,7] regarding the existence of C−H···O hydrogen bonding within a wide range of synthetic and naturally occurring compounds, this “weak” interaction has become a well-accepted axiom
A recent report which describes the role of the intramolecular C−Hα···O contact of chiral lactams in their spatial arrangement—both in solution and in solid state [23]—have attracted our attention, especially because this chiral auxiliary is frequently employed in asymmetric synthesis [24]
The current theoretical study of a set of cyclic amides derived from α-methylbenzylamine attempts to further advance towards the understanding of the origin and the nature of this C−Hα···O hydrogen bonding
Summary
With the vast theoretical and experimental contributions coming from the laboratories of Desiraju [1,2,3], Steiner [4,5], and Scheiner [6,7] regarding the existence of C−H···O hydrogen bonding within a wide range of synthetic and naturally occurring compounds, this “weak” interaction has become a well-accepted axiom. Today its relevance and importance in chemistry is fundamental to the interpretation and understanding of molecular conformation (either in solution or in the solid state [8]) and of chemical transformations in solution This interaction does not usually exceed 3 kcal/mol [9,10], it plays a crucial role in favoring crystallization [11,12], conformational equilibrium [13,14] or inducing selectivity [15,16,17,18,19,20,21,22].
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