Synthesis of (macro)heterocycles by consecutive/repetitive isocyanide-based multicomponent reactions.

Angélica De Fátima S Barreto,Carlos Kleber Z Andrade

doi:10.3762/bjoc.15.88

Abstract

Isocyanide-based multicomponent reactions are a versatile tool in the synthesis of heterocycles. This review describes recently developed approaches based on the combination of consecutive or repetitive isocyanide-based multicomponent reactions for the synthesis of structurally diverse heterocycles. These strategies have also allowed the synthesis of a plethora of macroheterocycles in a reduced number of steps.

Highlights

Isocyanide chemistry was first described by Lieke in 1859 [1] and forms the basis of a large group of reactions in organic chemistry, especially in isocyanide-based multicomponent reactions (IMCRs) [2,3], such as the Passerini and Ugi reactions, which are reactions that have been widely used in the synthesis of peptides, peptidomimetics and heterocycles [4,5,6,7,8]
We describe synthetic sequences involving repetitive or consecutive IMCRs that have provided molecules with even more structural diversity
Scheme 14: a) Synthetic sequence for accessing diverse macrocycles containing the tetrazole nucleus by the union of two IMCRs. b) Some compounds obtained by this strategy [30]

Summary

Introduction

Isocyanide (isonitrile) chemistry was first described by Lieke in 1859 [1] and forms the basis of a large group of reactions in organic chemistry, especially in isocyanide-based multicomponent reactions (IMCRs) [2,3], such as the Passerini and Ugi reactions, which are reactions that have been widely used in the synthesis of peptides, peptidomimetics and heterocycles [4,5,6,7,8]. The synthetic strategy was based on two hydrazino-Ugi-azide reactions and a hydrazinolysis step for the synthesis of acylhydrazino bis(1,5-disubstituted tetrazoles). Another recent study carried out the synthesis of tetrazole peptidomimetics by the direct use of unprotected amino acids in two consecutive Ugi-type reactions [24].

Results

Conclusion