1-alkoxyamino-2-nitroalkanes as key building blocks for a chemo- and diastereoselective synthesis of a new type of polyfunctionalized N-alkoxypiperidine

Abstract

A highly efficient conversion of β-nitrostyrenes into a new kind of functionalized N-alkoxy-2-hydroxypiperidine in two steps was developed, giving excellent yields and diastereoselectivity. The prepared compounds are the first examples of N-alkoxy-2-hydroxypiperidines. The synthetic approach involved the conjugate addition of alkoxyamines to β-nitrostyrenes, followed by Michael addition of the isolated nitroalkoxyamines to α,β-unsaturated carbonyl compounds, and intramolecular addition of the alkoxyamino group to the carbonyl functionality of the (non-isolated) adducts. Although three stereogenic centers are formed, only one diastereoisomer was detected. This unprecedented sequence of reactions can also be performed in a one-pot fashion.