Mechanisms of Stereodirecting Participation and Ester Migration from Near and Far in Glycosylation and Related Reactions.

This review is the counterpart of a 2018 Chemical Reviews article (Adero, P. O.; Amarasekara, H.; Wen, P.; Bohé, L.; Crich, D. Chem. Rev. 2018, 118, 8242-8284) that examined the mechanisms of chemical glycosylation in the absence of stereodirecting participation. Attention is now turned to a critical review of the evidence in support of stereodirecting participation in glycosylation reactions by esters from either the vicinal or more remote positions. As participation by esters is often accompanied by ester migration, the mechanism(s) of migration are also reviewed. Esters are central to the entire review, which accordingly opens with an overview of their structure and their influence on the conformations of six-membered rings. Next the structure and relative energetics of dioxacarbeniun ions are covered with emphasis on the influence of ring size. The existing kinetic evidence for participation is then presented followed by an overview of the various intermediates either isolated or characterized spectroscopically. The evidence supporting participation from remote or distal positions is critically examined, and alternative hypotheses for the stereodirecting effect of such esters are presented. The mechanisms of ester migration are first examined from the perspective of glycosylation reactions and then more broadly in the context of partially acylated polyols.

Diversity-Oriented Synthesis of N,N,O-Trisubstituted Hydroxylamines from Alcohols and Amines by N-O Bond Formation.

Magnesium dialkylamides react with alcohol-derived 2-methyl-2-tetrahydropyranyl alkyl peroxides (MTHPs) in tetrahydrofuran at 0 °C to give N,N,O-trisubstituted hydroxylamines suitable for medicinal chemistry purposes in good to excellent yields. A wide range of secondary alkyl and aryl amines and primary and secondary alcohol-derived MTHPs are compatible with the described reaction which, coupled with the enormous diversity of commercially available alcohols and secondary amines, suggests broad applicability of the reaction in fragment-based library design.