Oxidation of N,N-Disubstituted Hydroxylamines to Nitrones: The Search for More Sustainable Selective and Practical Stoichiometric Oxidants

Abstract

Nitrones are key intermediates for the total synthesis of nitrogen-containing natural products and analogues. The direct oxidation of the corresponding N,N-disubstituted hydroxylamines is one of the most straightforward methods to access such compounds. In this account, we describe the state of the art of this oxidative transformation using stoichiometric reagents. We will focus on the efforts made in the last 25 years to oxidize polyhydroxylated cyclic hydroxylamines, due to our long-standing interest in the total synthesis of alkaloids and other glycomimetics. Particular attention will be devoted to the discussion of the regioselectivity issue arising when unsymmetrical and highly functionalized substrates are involved.