Tandem Catalysis: Synthesis of Nitrogen-Containing Heterocycles

Joana F Campos,Sabine Berteina-Raboin

doi:10.3390/catal10060631

Abstract

In this Review, we consider all the publications since the beginning of the century that describe tandem reactions resulting in the formation of five-membered aromatic nitrogen heterocycles (thiazole, imidazole, indole, tetrazole, triazole, and isoxazole). The contents of this review are organized by taxonomy and type of tandem catalysis. It covers orthogonal, auto-, and assisted tandem catalysis, providing an overview of tandem reactions applied tonitrogen heterocycles reported in the literature up to March 2020. We believe that this compilation of data will provide a necessary starting reference to developthe applications of tandem catalysis in medicinal chemistry.

Highlights

As showcased by the examples in this review, tandem catalysis can be a valid tool for medicinal chemists because of the high atom economy generated
Tandem reactions have often been used in the total synthesis sequences of natural products, and we have seen its applicability to interesting heterocyclic substrates
In which several catalysts and reagents are combined in a single reaction flask with a sequence of catalytic steps, are attractive from the point of view of reducing waste and time

Summary

Introduction

1. IntTrhoeduccotniocenpt of drug‐like space is widely used in modern medicinal chemistry. LoKcekys socfamffoolsdt cdormugpsoonnenthtseinmmarekdetictiondaal yc.hNemitirsotgryenarheetthereorciyncglessy(sFteigmusr,eth1)eafruenadmamonegnttahlebustirludcintugrablloccokms poofnmenostst dmrousgts ocnomthme monalryketfotoudnady. Ammononlyg tuhseedfivien-mthemisbcelraesds aarroem: aTtihcianzitorloeg, einmhidetaezroolcey,cliensd,othlee, ttoetprafizvoelem, oasntdcobmenmzoimnliyduazseodlei.nTthheisseclafisvsearme:aTinhiaarzoomlea,tiimc ihdeatzeorolec,yincldeoslae,reteftorauznodlei,nanadhbuenndzrimediddarzuogles. T[1h,2e]s.e five main aromatic heterocycles are found in a hundred drugs [1,2]. GThiniscrpeaapseinrgislya cimompoprrteahnetnfsoivresryenvtihewesiozfinthgemstouldeiceuslerseptohrattedairne threelelivtaenrattuforer fCraotamlys2ts020200t,o10M, xa; drcohi: F2O0R20PEthERatRmEVeInEtWion tandem reactions generating five-mwemwwbe.mreddpia.croomm/joautricnanl/ictartoalgyestns heterocycles: Thiazole, imidazole, indole, tetrazole, triazole, and isoxazole. Catalysts 2020, 10, 631; doi:10.3390/catal10060631 www.mdpi.com/journal/catalysts medicinal chemistry. This paper is a comprehensive review of the studies reported in the literature from 2000 to March 2020 that mention tandem reactions generating five‐membered aromatic nitrogen heterocycles: Thiazole, imidazole, indole, tetrazole, triazole, and isoxazole

Taxonomy

TTandem Catalysis

OOrrthhoggonal Tandem Catalysis

Auto‐Tandem Catalysis

NN X NN N RR33

Conclusions