Recent advances in the electrochemical construction of heterocycles

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.

Keywords: anodic cyclization; electrosynthesis; heterocycle; olefin coupling; organic electrochemistry; radical cyclization.

Figure 1

Common types of electrochemically induced cyclization reactions.

Scheme 1

Principle of indirect electrolysis.

Scheme 2

Anodic intramolecular cyclization of olefines in methanol.

Scheme 3

Anodic cyclization of olefines in CH₂Cl₂/DMSO.

Scheme 4

Intramolecular coupling of 1,6-dienes in CH₂Cl₂/DMSO.

Scheme 5

Cyclization of bromopropargyloxy ester 12.

Scheme 6

Proposed mechanism for the radical cyclization of bromopropargyloxy ester 12.

Scheme 7

Preparation of pyrrolidines and tetrahydrofurans via Kolbe-type electrolysis of unsaturated carboxylic acids 16.

Scheme 8

Anodic cyclization of chalcone oximes 19.

Scheme 9

Generation of N-acyliminium (23) and alkoxycarbenium species (24) from amides and ethers with and without the use of electroauxiliaries.

Scheme 10

Anodic cyclization of dipeptide 25.

Scheme 11

Anodic cyclization of a dipeptide using an electroauxiliary.

Scheme 12

Anodic cyclization of hydroxyamino compound 29.

Scheme 13

Cyclization of unsaturated thioacetals using the ArS(ArSSAr)⁺ mediator.

Scheme 14

Cyclization of biaryl 35 to carbazol 36 as key-step of the synthesis of glycozoline (37).

Scheme 15

Electrosynthesis of 39 as part of the total synthesis of alkaloids 40 and 41.

Scheme 16

Wacker-type cyclization of alkenyl phenols 42.

Scheme 17

Cathodic synthesis of indol derivatives.

Scheme 18

Fluoride mediated anodic cyclization of α-(phenylthio)acetamides.

Scheme 19

Synthesis of 2-substituted benzoxazoles from Schiff bases.

Scheme 20

Synthesis of euglobal model compounds via electrochemically induced Diels–Alder cycloaddition.

Scheme 21

Cycloaddition of anodically generated N-acyliminium species 58 with olefins and alkynes.

Scheme 22

Electrochemical aziridination of olefins.

Scheme 23

Proposed mechanism for the aziridination reaction.

Scheme 24

Electrochemical synthesis of benzofuran and indole derivatives.

Scheme 25

Anodic anellation of catechol derivatives 66 with different 1,3-dicarbonyl compounds.

Scheme 26

Electrosynthesis of 1,2-fused indoles from catechol and ketene N,O-acetals.

Scheme 27

Reaction of N-acyliminium pools with olefins having a nucleophilic substituent.

Scheme 28

Synthesis of thiochromans using the cation-pool method.

Scheme 29

Electrochemical synthesis and diversity-oriented modification of 73.