Barton–Zard reaction explained

The Barton–Zard reaction is a route to pyrrole derivatives via the reaction of a nitroalkene with an α-isocyanide under basic conditions.^[1] It is named after Derek Barton and Samir Zard who first reported it in 1985.^[2]

Mechanism

The mechanism consists of five steps:

• Base catalyzed carbonyl enolization of the α-isocyanide.
• Michael-type addition between the α-isocyanide carbonyl enolate and the nitroalkene.
• 5-endo-dig cyclization (see: Baldwin's rules).
• Base catalyzed elimination of the nitro group.
• Tautomerization leading to aromatisation.

Scope

The nitro compound may be aromatic rather than just an alkene.^[3] The reaction has been used for the synthesis of polypyrroles, including porphyrins,^[4] as well as dipyrromethenes such as BODIPY.^[5]

Notes and References

1. Book: Jie Jack Li . Heterocyclic Chemistry in Drug Discovery . Wiley . New York . 2013 . 9781118354421. pp.43-4
2. Barton. Derek H. R.. Zard. Samir Z.. A new synthesis of pyrroles from nitroalkenes. Journal of the Chemical Society, Chemical Communications. 1985. 16. 1098. 10.1039/C39850001098.
3. Lash. Timothy D.. Novak. Bennett H.. Lin. Yanning. Synthesis of phenanthropyrroles and phenanthrolinopyrroles from isocyanoacetates: An extension of the barton-zard pyrrole condensation. Tetrahedron Letters. April 1994. 35. 16. 2493–2494. 10.1016/S0040-4039(00)77152-8.
4. Finikova. Olga S.. Cheprakov. Andrei V.. Beletskaya. Irina P.. Carroll. Patrick J.. Vinogradov. Sergei A.. Novel Versatile Synthesis of Substituted Tetrabenzoporphyrins. The Journal of Organic Chemistry. January 2004. 69. 2. 522–535. 10.1021/jo0350054. 14725469.
5. Ono. Noboru. Barton-Zard Pyrrole Synthesis and Its Application to Synthesis of Porphyrins, Polypyrroles, and Dipyrromethene Dyes. Heterocycles. 2008. 75. 2. 243. 10.3987/REV-07-622. free.