Barton-Zard synthesis

Cyclocondensation of nitroalkenes with CH-acidic isocyanides in the presence of bases leads to the formation of trisubstituted pyrroles 20 (Barton-Zard synthesis) [43] ... 

Disubstituted pyrroles are important building blocks for porphyrin synthesis (cf p. 553). With two equal 3,4-substituents, they can be straightforwardly obtained by the Piloty-Robinson synthesis [118] ofhigher flexibility are isocyanide-based methods like the Barton-Zard synthesis [119] and the Van Leusen synthesis [120]. 

Baker-Venkataraman rearrangement 338 Balaban synthesis (pyrylium ion) 302 Bamberger-Hughes-Ingold rearrangement 350 Barton-Zard synthesis (pyrrole) 120 Batcho-Leimgruber synthesis (indole) 136 Baylis-Hillman reaction 452 Beirut reaction 254, 500 Bemthsen synthesis... 

The Barton-Zard (BZ) pyrrole synthesis is similar both to the van Leusen pyrrole synthesis that uses Michael acceptors and TosMlC (Section 6.7) and the Montforts pyrrole synthesis using a,P-unsaturated sulfones and alkyl a-isocyanoacetates." An alternative to the use of the reactive nitroalkenes 1 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. Examples are shown later. 

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... 

The combination of the Diels-Alder reaction of fi-sulfonylnitroethylene and the Barton-Zard reaction provides a new synthesis of pyrroles fused with polycyclic skeletons fEq 10 31 Pyrroles fused with bicycle [3 3 3 Qctodiene are important precursors for synthesis of isoindoles via the retro Diels-Alder reaction fEq 10 33 ... 

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. 

Aida and coworkers have used the Barton-Zard reaction in the synthesis of axially dissymmetric pyrroles as shown in Eq. 10.30.35... 

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... 

This synthesis of octaethylporphyrin, widely used as a model compound, uses a Barton-Zard sequence and leads to a pyrrole-2-ester which is then hydrolysed and decarboxylated. 

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

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