Epoxidation of trans-4-Aminocyclohex-2-en-1-ol Derivatives: Competition of Hydroxy-Directed and Ammonium-Directed Pathways

N-Substituted trans-4-aminocyclohex-2-en-1-ols undergo epoxidation upon treatment with Cl3CCO2H followed by meta-chloroperbenzoic acid (m-CPBA) via competitive pathways resulting from hydrogen-bonding delivery by both the hydroxy group and the in situ formed ammonium ion. The absence of epoxide ring-opening in these reactions renders these substrates a unique platform for analysing the effect of the two competing directing groups on the rate of the epoxidation reaction: the diastereoisomeric ratio of the epoxide products is also the ratio of the rate constants describing the competing epoxidation processes (the group with the higher directing ability dominating the stereochemical course of the reaction). Analysis of the diastereoisomeric epoxide mixtures obtained from these reactions allowed the following order of directing group ability to be defined: NHBn >> NMeBn > OH > NBn2. The large difference in rate between the secondary and tertiary amino groups is consistent with superior directing ability of the former due to the presence of two hydrogen-bond donor sites on the secondary ammonium ion and/or an increased conformational flexibility to adopt an optimum geometry. The rate of an ammonium-directed epoxidation proceeds similar to 10 times slower in the presence of an allylic hydroxy group than in its absence, consistent with the presence of the additional, inductively electron-withdrawing heteroatom abating the nucleophilicity of the olefin. The relative rate of the hydroxy-directed epoxidation process in the presence of a more sterically demanding ammonium substituent is greater than that in the presence of a less sterically demanding one: this effect is attributed to an increased bias for the half-chair conformer in which the bulky ammonium substituent and, hence, the hydroxy group occupy pseudo-equatorial sites, thus allowing the latter to direct the reaction more efficiently.