Generalized anomeric effect of α-chloro-O-oxime ethers; influence of various substitutions by DFT, NBO and AIM studies

Abstract

α-Halo-O-oxime ethers have been reported to be the key intermediates in the synthesis of O-oxime ethers. Their stability has a very important role in the synthesis possibility and the product yield, and the anomeric effect is the main factor representing their stability. The density functional theory (DFT) has been used to investigate the effect of various substitutions (R1/R2=CH3, CF3, t-But, OMe, N(Me)2) with different induction or resonance influences on the anomeric effect of α-chloro-O-oxime ethers. The results from the natural bond orbital (NBO) and atoms in molecules (AIM) analyses have been discussed and useful comparisons have been carried out. All calculations at B3LYP level with 6-31G(d,p) and 6-311G(d,p) basis sets, also at correlation method CCSD/6-31G(d,p)//B3LYP/6-311G(d,p), show that in all compounds the gauche conformers are the most stable conformation, and the reasons have been attributed to the hyperconjugation and steric effects. The NBO analyses show that increasing the electron-donating strength of the substitutions in R1 and/or R2 positions leads to more charge transfer from the lone pairs of the oxygen atom to the C–Cl anti-bonding sigma orbital, which results in more amount of the anomeric effect. It has been shown that the LPO→πN–C∗ interaction could be considered as a lowering factor for the anomeric effect in these compounds. The influences of substituting in different R1 and R2 positions on the anomeric effect of the studied compounds have been also investigated. The AIM studies on the topological properties of the bond critical point (BCP) of the C–Cl and C–O bonds in the studied compounds confirm the results of the NBO and structural analyses.