Energy Decomposition Analysis Reveals the Nature of Lone Pair-π Interactions with Cationic π Systems in Catalytic Acyl Transfer Reactions

Abstract

Lone pair-π (LP-π) interactions between Lewis basic heteroatoms, such as oxygen and sulfur, and electron-deficient π systems are important noncovalent interactions. However, they have seldom been used to control catalyst-substrate interactions in catalysis. We performed density functional theory calculations to investigate the strengths of LP-π interactions between different lone pair donors and cationic π systems, and in different complexation geometries. Energy decomposition analysis calculations indicated that the dominant stabilizing force in LP-π complexes is electrostatic interaction and the electrostatic potential surface of the π system predicts the most favorable site for forming LP-π complexes. Benzotetramisole (BTM) is revealed as a privileged acyl transfer catalyst that promotes LP-π interactions because the positive charge of the acylated BTM is delocalized onto the dihydroimidazole ring, which binds strongly with a variety of oxygen and sulfur lone pair donors.

Figure 1.

a) Lone pair-π interactions and their applications in structural biology and catalysis. b) (R)-BTM-catalyzed site-selective acylation of glucosides.

Figure 2.

(a) Binding energies (ΔE, in kcal/mol) of LP-π complexes of water with Ac-BTM calculated at the M06-2X/(O, S: 6-311+G(d,p); H, C, N: 6-311G(d,p))/SMD(chloroform)//M06-2X/6-31G(d) level of theory. (b) Energy decomposition analysis of the LP-π binding energy. (c) Effects of vertical distance (d_v) and dihedral angle (θ) on ΔE. (d) LP-π interactions in acylation transition states reported in Ref. .