Ruthenium and Iron-Catalysed Decarboxylative N-alkylation of Cyclic α-Amino Acids with Alcohols: Sustainable Routes to Pyrrolidine and Piperidine Derivatives.

Anastasiia Afanasenko,Saravanakumar Elangovan,Tao Yan,Rachael Hannah,Katalin Barta

doi:10.1002/cssc.201901499

Anastasiia Afanasenko, Saravanakumar Elangovan + Show 3 more

Open Access

https://doi.org/10.1002/cssc.201901499

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Journal: ChemSusChem	Publication Date: Jul 22, 2019
Citations: 18	License type: CC BY 4.0

Affiliation: University of Groningen

Abstract

A modular and waste‐free strategy for constructing N‐substituted cyclic amines via decarboxylative N‐alkylation of α‐amino acids employing ruthenium‐ and iron‐based catalysts is presented. The reported method allows the synthesis of a wide range of five‐ and six‐membered N‐alkylated heterocycles in moderate‐to‐excellent yields starting from predominantly proline and a broad range of benzyl alcohols, and primary and secondary aliphatic alcohols. Examples using pipecolic acid for the construction of piperidine derivatives, as well as the one‐pot synthesis of α‐amino nitriles, are also shown.

Highlights

Saturated azaheterocycles, especially pyrrolidine and piperidine, are ubiquitous scaffolds in biologically active compounds[1] and key building blocks in diverse areas of organic chemistry.[2]
The formation of oxazolidones by reaction of a-amino acids with carbonyl compounds was previously extensively investigated by Grigg et al.[17b] and Seebach et al.[18] whereas oxazolidone/iminium equilibria were proposed during mechanistic studies of proline-mediated aldol condensation reactions.[19]
We have developed the decarboxylative N-alkylation of aamino acids with alcohols applying Ru- and Fe-based catalytic systems for the synthesis of N-substituted cyclic amines

Summary

Introduction

Especially pyrrolidine and piperidine, are ubiquitous scaffolds in biologically active compounds[1] and key building blocks in diverse areas of organic chemistry.[2]. A highly interesting approach for the one-pot construction of valuable N-heterocyclic scaffolds would be the combination of the hydrogen-borrowing with the decarboxylation/azomethine ylide chemistry: this would enable the catalytic coupling of naturally abundant amino acids with widely available and potentially bio-derived alcohol substrates (Scheme 1 c). In this case, the carbonyl compounds necessary for imine formation. First decarboxylative N-alkylation methods using these Fe- and Ru-based half-sandwich complexes

Results and Discussion

Conclusions

Conflict of interest