Barton–Zard reaction

The Barton-Zard reaction is a route to pyrrole derivatives via the reaction of a nitroalkene with an α-isocyanoacetate 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 enolizaton 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.
• 1,5-sigmatropic rearrangement 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]

References

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