One‐Pot Synthesis of O‐Allylhydroxylamines through the Organocatalytic Oxidation of Tertiary Allylic Amines Followed by a [2,3]‐Meisenheimer Rearrangement

Abstract

A cheap, green, and highly efficient one-pot method for the synthesis of O-protected allylic alcohols is described. By utilizing 2,2,2-trifluoroacetophenone as the organocatalyst and H2 O2 as the oxidant, a variety of allylic amine N-oxides were synthesized, which upon heating are converted to the final products through a [2,3]-Meisenheimer rearrangement.

Green Organocatalytic Oxidative Methods using Activated Ketones

“…In 2015, Kokotos and co‐workers proposed a one‐pot synthesis of o ‐allylhydroxylamines through the organocatalytic oxidation of tertiary allylic amines followed by a [2,3]‐Meisenheimer rearrangement . This kind of rearrangement is a very common reaction in the synthesis of natural products and potential antiviral agents (Scheme )…”

“…[123] The most commonm ethodf or the synthesis of these compounds is the oxidation of amines by using peracids, [124a-b] In 2015, Kokotos andc o-workersp roposed ao ne-pot synthesis of o-allylhydroxylamines through the organocatalytic oxidation of tertiary allylic amines followed by a[ 2,3]-Meisenheimerr earrangement. [125] This kind of rearrangement is av ery common reactioni nt he synthesis of natural products andp otential antiviral agents (Scheme 35). [126] In the same year,K okotos and co-workersp roposed the organocatalytic oxidation of sulfidest os ulfoxides and sulfones, [127] which are very importantm oieties used in medicinal chemistry,b yu sing the group's oxidation protocol.…”

Organocatalytic Synthesis of Oxazolines and Dihydrooxazines from Allyl‐Amides: Bypassing the Inherent Regioselectivity of the Cyclization

“…A few years ago, we identified 2,2,2‐trifluoroacetophenone as the appropriate organocatalyst for hydrogen peroxide activation. We initially demonstrated its use in the oxidation of heteroatoms, like silanes, tertiary amines and azines,, sulfides and anilines, where we studied also the reaction mechanism, excluding the possibility of the involvement of a dioxirane intermediate . Also, we have employed this oxidative protocol in the oxidation of alkenes and cyclization reactions .…”

Nonanebis (peroxoic acid)‐Mediated Transition‐Metal‐Free Approach for N‐Oxide Synthesis

“…Use of catalytic processes comprises various drawbacks such as leaching of metal catalyst, long reaction time,, and instability of catalyst at high temperature. In recent years various processes have been reported by using hydrogen peroxide as a key oxidant with transition metal catalyst such as trifluoroacetic anhydride, methyl rhenium trioxide, but due to its low reactivity towards N‐oxide synthesis, long reaction time and low yield of product has been major concern. Great efforts have been made to develop metal catalyst free approaches to synthesize various N‐oxides by using 2,2,2‐trifluroacetophenone as an Organocatalyst and 1,2‐diphenyl‐1,1‐2,2‐tetrahydroperoxyethane as an oxidant.…”