Barton-Zard pyrrole synthesis

The Barton-Zard pyrrole synthesis has now been extensively applied to synthesis of naniral and unnaniral products containing pyrrole units Methyl 4-methylpyrrole-3-carboxylate is the trail-maker pheromone of the Texas leaf-aitting ant Arm lexaiia It is readily prepared by the Barton Zard method in 60% yield fEq 10 33 ... 

Py rrolostatin is a novel lipid peroxidation inhibitor, which is isolated from Sirepinmyces diresinmyceiiois. Its stnicnire consists of a pyrrole-3-carboxyiic acid v/ith a geranyl group at the 4-posidon. It is readily prepared by applying the Barton-Zard pyrrole synthesis, as shown inEq. 10.33. ... 

Barton-Zard pyrrole synthesis is ffso applied to synthesis of pyrroles with a variety of subsdtuents Pyrroles subsdtuted with long ilkylsubsdtuents at the 3 and 4 posidons, pyrroles with fi-CF3 fEq 10 26, 3,4-diarypyrroles fEq 10 27i, and pyrrole-2-phophonates fEq 10 28are prepared in a sirtular matmer based on isonitnle cyclizadon... 

Barton-Zard pyrrole synthesis is also applied to synthesis of pyrroles with a variety of substituents. Pyrroles substituted with long alkyl substituents at the 3 and 4 positions,30 pyrroles with P-CF3 (Eq. 10.26),31 3,4-diarypyrroles (Eq. 10.27),32 and pyrrole-2-phophonates (Eq. 10.28)33 are prepared in a similar manner based on isonitrile cyclization. 

Nitroalkenes can be replaced by u. i-unsaturated sulfones in the Barton-Zard pyrrole synthesis. Each method has its own merit. Nitroalkenes are more reactive than a,(3-unsaturated sulfones therefore, nitroalkenes should be used in less reactive cases. On the other hand, cyclic u.fi-unsaturated sulfones are more easily prepared than cyclic nitroalkenes pyrrole synthesis using sulfones is the method of choice in such cases, as shown in Eq. 10.41.46... 

The Barton-Zard pyrrole synthesis <1990T7587> was applied in the syntheses of pyrrolo[3,4- ]indoles 423 from 3-nitroindoles 422. Treatment of appropriate alkyl 3-nitroindole-l-carboxylates 422a-c with ethyl isocyanoacetate and l,8-diazabicyclo[5.4.0]undec-7-ene (DBU) gave the corresponding pyrrolo[3,4- ]indole 423a-c (Equation 12) <1997CC1873, 1999S1117>. 

Cyclization of 3-nitroindoles 127 with ethyl isocyanoacetate and DBU (conditions of Barton-Zard pyrrole synthesis) gave the corresponding pyrrolo 3,4-fc]indoles 128 (Scheme 22) [35],... 

Several new examples of the Barton-Zard pyrrole synthesis from nitroalkenes and isocyanoacetate esters demonstrate the broad utility of this procedure. An excellent yield of ethyl 3-(9-anthryl)-4-ethylpyrrole-2-carboxylate was obtained starting with the nitroalkene from anthracene-9-carboxaldehyde and 1-nitropropane. <95TL8457> Bums et.al. reported an improved synthesis of benzyl isocyanoacetate which facilitates the synthesis of benzyl pyrrole-2-carboxylate esters by this method. <95SC379> 3-(l-Arylpyrrol-2-yl)pyrrole-2-carboxylates were prepared from l-aryl-2-(nitrovinyl)pyrroles. <95JHC 1703>... 

Barton-Zard pyrrole synthesis, 70, 75 Benzazepine, 70, 145 Benzazepinone, 70, 144... 

Barton-Zard pyrrole synthesis and its application to synthesis of porphyrins, polypyrroles and dipyrromethene dyes , Ono, N., Heterocycles, 2008, 75, 243. 

The Barton-Zard reaction refers to the base-induced reaction of nitroalkenes with alkyl a-isocyanoacetates to afford pyrroles. Solvents used are THF or alcohols (or mixtures), and the reaction often proceeds at room temperature. The Barton-Zard pyrrole synthesis is similar both to the van Leusen pyrrole synthesis that uses Michael acceptors and TosMIC and to the Montforts pyrrole synthesis that uses a,P unsaturated sulfones and alkyl a-isocyanoacetates. An alternative to the use of the reactive nitroalkenes is their in situ generation from P-acetoxy nitroalkanes, which are readily prepared via the Henry reaction between an aldehyde and a nitroalkane followed by acetylation. 

Other references related to the Barton-Zard pyrrole synthesis are cited in the literature. 

Gribble and Pelkey adapted the Barton-Zard pyrrole synthesis [84] to 3-nitroindoles and ethyl isocyanoacetate (and tosylmethyl isocyanide) to give 2,4-dihydropyrrolo [3,4-T [indoles (Scheme 15, equation 1) [85, 86], In complementary work, Gribble and cowoikers synthesized pyrrolo[3,4-fc]indoles from the 1,3-dipolar cycloaddition of 2- and 3-nitroindoles with miinchnones (1,3-oxazo-lium-5 elates) (eqnations 2, 3) [87, 88]. The mesoionic miinchnones were generated in situ from the appropriate Af-benzyl-Af-acylamino acids. Gribble and Kishbaugh... 

---