Using density functional theory to calculate the anomeric effect in hydroxylamine and hydrazide derivatives of tetrahydropyran

<p>Little is known about the magnitude of the anomeric effect in N-glycosylated oxyamines and hydrazides, limiting efforts toward the design of chemoselective acceptors that impose a stereochemical preference on glycosylation reactions. Thus, density functional theory (DFT) calculations were conducted to estimate the magnitude of the anomeric effect in <i>N,O</i>-dimethyl-<i>N</i>-(tetrahydro-<i>2H</i>-pyran-2-yl)hydroxylamine (<b>1</b>) and <i>N'</i>-(tetrahydro-<i>2H</i>-pyran-2-yl)acetohydrazide (<b>3</b>). The results show that <i>N,O</i>-dimethyl-<i>N</i>-(tetrahydro-<i>2H</i>-pyran-2-yl)hydroxylamine (<b>1</b>) displays a significant anomeric effect (AE<sub>corr</sub> = 1.38 kcal/mol) and that <i>N'</i>-(tetrahydro-<i>2H</i>-pyran-2-yl)acetohydrazide (<b>3</b>) displays a modest anomeric effect (AE<sub>corr</sub> = 0.54 kcal/mol).</p>