Barton-Zard condensation

The copper and nickel nitroporphyrins 6 (M = Cu, Ni) undergo pyrrole ring annulation with isocyanoacetates according to the Barton-Zard condensation originally designed for the preparation of simple monopyrroles112 (cf. Houben-Weyl, Vol.E6a, p650). 

The Barton Zard condensation is one more important and marvelous SnH heterocyclization leading to pyrrole ring annulation to nitroalkenes, nitroarenes or nitrohetarenes on being treated with alkyl isocyanoacetates in the presence of a base (85CC1098, 90T7587). The reaction starts with nucleophilic attack of alkyl isocyanoacetate carbanion 160 ortho to the NCT group of substrate 161. The... 

To enter the Barton-Zard condensation, a substrate must have essentially nitro-alkene character. This is the reason why the reaction with nitrobenzene fails and 1-nitronaphthalene also reacts slightly (94CC1019). An additional N02 group on the naphthalene ring substantially facilitates the transformation but the expected dipyrroles are not formed (95TL4381). Table 2 presents various substrates, the corresponding products and some other details of the Barton-Zard condensation. 

Nitropyridine 166 in the Barton-Zard condensation behaves specifically affording tricyclic compound 167 (00SL213). Evidently, 4-azaisoindole derivative 168 formed in the first step reacts further with another molecule of nucleophile that results in imidazole ring closure (Scheme 50). Under the same conditions 4-nitro-pyridine remains unchanged. 

Thus, it follows from Schemes 51 and 53 that heterocyclic substrates in the Barton-Zard condensation often behave anomalously. 

In conclusion, it should be noted that the Barton-Zard condensation formally might be considered as a tandem SnH-Sn ipso process (see Section III.B.3). However, the corresponding crH-complcx is stabilized here not via elimination of any auxiliary leaving group or oxidation but by means of an intramolecular nucleophilic attack on an isonitrile fragment. This is due to the amphoteric nature of isocyanoacetate ion acting at first as a nucleophile and then as an electrophile. 

Table 2. Substrates and products of the Barton-Zard condensation...

Two condensation approaches were developed for the synthesis of pyrrolo[2,3- pyrroles 50 (pyrrolo-prolines) <04JOC4656>, novel fused proline derivatives <04JA14334>. Finally, a solid-phase approach to isoxazolinopyrroles 51 was reported <04JCO142>. The key step involved a Barton-Zard-type pyrrole synthesis. 

C.M. Cillo et al. reported on the synthesis of porphyrins condensed with 2,1,3-benzoxa- and selenadiazoles [89]. Also pyrrolobenzodiazoles 114 were prepared by the Barton-Zard reaction from 4-nitrobenzofurazans or benzoselena-diazoles and isocyanoacetic esters in the presence of DBU (Scheme 51). 

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