Barton-Zard pyrrole synthesis

What is Barton-Zard pyrrole synthesis?

Barton and Zard first reported the Barton-Zard pyrrole synthesis in 1985, also known as the Barton-Zard pyrrole condensation or Barton-Zard reaction. This method synthesizes 2-substituted pyrroles (2-pyrrole-carboxylates or 2-sulfonyl pyrroles) through the basic condensation of alkyl isocyanoacetate (or tosylmethyl isocyanide) with α,β-unsaturated nitroalkenes (or β-nitroacetates).

This reaction is suitable for synthesizing pyrroles with various substituents at the β positions (R2 and R3), but it cannot be used for creating pyrroles lacking a substituent at position 2.

Barton-Zard pyrrole synthesis - Barton-Zard pyrrole condensation - Barton-Zard reaction
Barton-Zard pyrrole synthesis

Typically, the Barton-Zard pyrrole synthesis produces high yields (80–90%), except when R2 is hydrogen, in which case the yield is moderate. Nonionic strong bases like 1,8-diazabicyclo[5.4.0]undec-7-ene DBU and guanidine are usually employed. Currently, this method has been expanded to prepare polypyrroles and porphyrins fused with different aromatic rings or bicyclic frameworks, starting from aromatic nitro compounds and ethyl isocyanoacetate. These polypyrroles and porphyrins can serve as functional dyes.

The Barton-Zard pyrrole synthesis has been utilized to synthesize polypyrroles and porphyrins. While substituted isoindoles can also be produced from substituted nitrobenzenes, it is not possible to synthesize simple isoindoles in this way due to the lack of reactivity between nitrobenzene and ethyl isocyanoacetate.