Recent advances in the electrochemical construction of heterocycles.

Robert Francke

doi:10.3762/bjoc.10.303

Abstract

Due to the fact that the major portion of pharmaceuticals and agrochemicals contains heterocyclic units and since the overall number of commercially used heterocyclic compounds is steadily growing, heterocyclic chemistry remains in the focus of the synthetic community. Enormous efforts have been made in the last decades in order to render the production of such compounds more selective and efficient. However, most of the conventional methods for the construction of heterocyclic cores still involve the use of strong acids or bases, the operation at elevated temperatures and/or the use of expensive catalysts and reagents. In this regard, electrosynthesis can provide a milder and more environmentally benign alternative. In fact, numerous examples for the electrochemical construction of heterocycles have been reported in recent years. These cases demonstrate that ring formation can be achieved efficiently under ambient conditions without the use of additional reagents. In order to account for the recent developments in this field, a selection of representative reactions is presented and discussed in this review.

Highlights

The construction of heterocyclic cores undoubtedly represents a highly important discipline of organic synthesis
Much progress has been made in the electrochemical synthesis of heterocyclic compounds since Tabaković's review appeared in 1997
The emergence of the cation-pool method has significantly expanded the toolbox of the electrochemist with regard to the synthesis of heterocyclic compounds

Summary

Introduction

The construction of heterocyclic cores undoubtedly represents a highly important discipline of organic synthesis. Recent efforts in electrochemical heterocycle synthesis can mostly be differentiated into anodic olefin coupling (section 1.1), radical cyclization (section 1.2), and trapping of anodically generated iminium/alkoxycarbenium ions (section 1.3). Cycloadditions (section 2.1), sequential Michael addition/ring closure with in situ generated quinones (section 2.2) and sequential cyclizations involving acyliminium species and alkoxycarbenium ions (section 2.3) represent the majority of recently reported intermolecular electrochemical cyclizations. With regard to heterocycle synthesis, both direct electrolysis involving heterogeneous electron transfer between electrode and substrate as well as indirect electrolysis using electron transfer mediators (Scheme 1) play an important role. With a discrete electron transfer (outer-sphere mechanism) or proceed via bond formation (inner-sphere mechanism), depending on the type of mediator [31] In both cases, the electrode reaction proceeds at such a low potential that the substrate is electrochemically inactive.

Intramolecular cyclizations

Intermolecular cyclizations

Findings

Conclusion