Barton-Zard pyrrole reaction

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. 

The Barton-Zard reaction refers to the base-induced reaction of nitroalkenes 1 with alkyl a-isocyanoacetates 2 to afford pyrroles 3. Solvents used are THF or alcohols (or mixtures) and the reaction often proceeds at room temperature. 

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 ... 

DBU IS most widely employed as the base m the Barton-Zard reaction Stronger nonionic bases such as PrMeNCH-,CH-j,N and the phosphazene base Csiipplied by Flukai are more effective to induce pyrrole formadon in the reaction of nitroalkenes v/ith isocyano esters than DBU Sterically hindered nitroalkenes are converted into the corresponding pyrroles using these bases, as shovm in Eq 10 35, but DBU is not effective in this transformation... 

Heterocyclic aromatic nitro compounds are more reactive toward nucleophiles than carbo-cyclic aromatic nitro compounds Various heterocyclic aromatic nitro compounds are thus converted into the corresponding pyrroles by the Barton-Zard reaction fEq 10 37 ... 

The reaction pathways for the pyrrole formation are summarized in Scheme 10.3. The group that is eliminated at the final stage is a nitrite ion (Barton-Zard reaction) or a toluenesulfinate ion (Leusen reaction), depending on the reaction pattern. 

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

Polymer-supported reagents and other solid sequestering agents may be used to generate an array of 1,2,3,4-tetrasubstituted pyrrole derivatives using the Barton-Zard reaction as a key pyrrole formation reaction. Pure pyrroles are obtained without any chromatographic purification... 

Pyrroles prepared by the Barton-Zard reaction are very important as precursors of porphyrins and also of conducting polymers. The ester group at the 2-position is readily removed on heating with KOH in ethylene glycol at 170 °C to give a-free pyrroles, which are useful for preparing porphyrins (Eq. 10.42)47 or polypyrroles (Eq. 10.43).38a,4S... 

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... 

It is a common point of view that the Barton-Zard reaction is a favorable one for the pyrrole synthesis. It is based on interaction of conjugated nitroalkenes with isocyanoacetates in the presence of a base [6, 74-76] and, basically, involves three steps (Scheme 43) the Michael-type addition of isocyanide carbanion to the C=C double bond of nitroalkene, cyclization of the resulting anion to give pyrroline derivative, and elimination of the nitrite anion followed by aromatization. 

From the data considered above it is clear that the Barton-Zard ccmdensation of nitroarenes is a convenient method for the synthesis of polycyclic compounds of the isoindole family. Formally the reaction involves the process and further cyclization into the pyrrole ring accompanied by elimination of HNOa-... 

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... 

Ethano-bridged phthalate ester 56 was obtained by the DA reaction in good yield and was converted to the BCOD-fiised triester 57a, the t-butyl ester group of which was removed by treatment with TFA (Scheme 15.10) [63]. The DA reaction of tosylacetylene (5a) and 2-methoxy-l,3-cyclohexadiene proceeded smoothly to afford a diastereomeric mixture (5 1) of bicyclo[2.2.2]octenone 58 in 73% yield after hydrolysis by silica gel [64]. Diastereomeric 58 was quantitatively converted to dithiolane, which was subject to the ring expansion reaction with tellurium tetrachloride [65]. Dihydro-1,4-dithiin 59 was obtained in 74% yield. The Barton-Zard reaction of 59 with ethyl isocyanoacetate afforded pyrrole-carboxylate 60a (77% yield), which was transformed to both a-hydroxymethylpyrrole 60b and a-firee pyrrole 60c in good yields. 

In 1985, in the course of their interest in nitroalkane chemistry, Barton and Zard reported the base-catalyzed reaction of nitroalkenes with a-isocyanoacetates leading to pyrrole esters having an ideal substitution pattern for the synthesis of porphyrins and bile... 

Ono and Lash have been the two pioneers in applying the BZ reaction to the synthesis of pyrroles and, particularly, with applications to the synthesis of novel fused and other porphyrins. Although the concept was recognized by Barton and Zard, Ono and Lash independently discovered the conversion of 2-pyrrolecarbo ylates, prepared by the BZ reaction, into porphyrins by what is now a standard protocol (1. LiAlfL 2. 3. 

Barton and Zard found that the base-catalyzed reaction of nitroalkenes or P-nitroacetates with alkyl isocyanoacetate or TosMIC gives pyrrole-2-carboxylates or 2-sulfonylpyrroles, respectively (see Eqs. 10.18 and 10.19).22 This reaction is very convenient for the synthesis of... 

In addition to Scheme 20, the synthesis of (5,(5 -substituted pyrroles has also been achieved through a Zard-Barton reaction (1985JCS(CC)1098, 1990T7587, 1991SL127). Likewise, Hayashi et al. (03OL2845, 03IC7345)... 

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