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. 2014 May 12;53(20):5179-82.
doi: 10.1002/anie.201311165. Epub 2014 Apr 1.

Redox-neutral α,β-difunctionalization of cyclic amines

Weijie Chen  1 , YoungKu Kang, Richard G Wilde, Daniel Seidel
Affiliations

Redox-neutral α,β-difunctionalization of cyclic amines

Weijie Chen et al. Angew Chem Int Ed Engl. .

Abstract

In contrast to the continuously growing number of methods that allow for the efficient α-functionalization of amines, few strategies exist that enable the direct functionalization of amines in the β-position. A general redox-neutral strategy is outlined for amine β-functionalization and α,β-difunctionalization that utilizes enamines generated in situ. This concept is demonstrated in the context of preparing polycyclic N,O-acetals from simple 1-(aminomethyl)-β-naphthols and 2-(aminomethyl)-phenols.

Keywords: CH functionalization; azomethine ylides; enamines; heterocycles; redox neutrality.

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Figures

Scheme 1
Scheme 1
Concepts for the redox-neutral amine α-functionalization, β-functionalization and α,β-difunctionalization.
Scheme 2
Scheme 2
Experiments designed to determine the course of the annulation reaction and proposed mechanism.
Scheme 3
Scheme 3
Product modification.
Chart 1
Chart 1. Substrate scope for the α,β-difunctionalization/N,O-acetal formation.[a–c]
[a] Reactions were performed on a 0.5 mmol scale. [b] Substrates containing pyrrolidine and piperidine/morpholine moieties were heated at 200 and 250 °C, respectively. [c] Yields are combined yields of both diastereomers (if any), major diastereomer shown.
See this image and copyright information in PMC

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