Alkylations nitroalkenes, pyrrole

Scheme 6.64 AFC alkylation of pyrroles with nitroalkenes catalyzed by (5,S)-143 reported by Wang.

Blechert, Thomas, and co-workers developed a microporous recyclable heterogeneous catalyst 155 based on chiral phosphoric acid, which has been utilized in transfer hydrogenation, aza-ene-type reaction, and AFC alkylation of pyrrole. In the presence of 5 mol% polymer-supported catalyst 155, the AFC alkylation of pyrrole with nitroalkene occurred smoothly to afford the desired product in 91% yield with 96% ee (Scheme 6.71). 

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 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. 

Barton and Zard found that the base-catalyzed reacdon of nitroalkenes or fi-n v/ith alkyl isocyanoacetate or TosMIC gives pyrrole-3-carboxylates or 3-suifonylpyrroles, respecdvely fsee Eqs 10 18 and 10 19) This reacdon is very convenient for the synthesis of... 

Base-induced reaction of nitroalkenes with alkyl a-isocyanoacetates to afford pyrroles. 

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... 

Pyrrole synthesis. A new route to pyrroles1,2 is based on a base-catalyzed Michael addition of an alkyl isocyanoacetate to a nitroalkene to give an intermediate that cyclizes to a pyrrole. The nitroalkene is generally obtained from a P-acetoxy nitroalkane (1), prepared by a nitro aldol reaction of an aldehyde with a nitroalkane. The synthesis of ethyl 3,4-diethylpyrrole-2-carboxylate (2) is typical. 

The oxidation of the alcohol was performed with supported perruthenate (8.48, Fig. 8.46) to produce clean aldehydes 8.91 after filtration. The Henry reaction was performed in the presence of a commercially available, supported strong base 8.92 and an excess of volatile nitroalkenes, giving clean nitroalcohols 8.93 after filtration and evaporation. The reaction mixtures from the trifluoroacetylation/elimina-tion steps were purified with commercially available amino PS resin 8.58 to scavenge the trifluoroacetates and with acidic ion-exchange resin 8.76 to remove the TEA-derived salts. Again, the nitrostyrenes 8.94 were obtained cleanly after filtration and evaporation. Cycloaddition with isocyanoacetate was promoted by the commercially available, supported guanidine base 8.95, while the subsequent N-alkylation of the pyrroles 8.96 was performed with an excess of halide in the presence of the commercially available, supported phosphazene 8.97. In this case, the excess halide was removed by treatment with supported 8.58, and filtra-... 

Owing to its Lewis acidity, zinc complex 106 lends itself to schemes for alkylation of electron-rich arenes and heteroarenes such as pyrroles by way of conjugate addition. An even more valuable method is the 3-component condensation that unites indole with a nitroalkene and an aldehyde. Three contiguous stereocenters are established in a controlled manner and in an absolute sense by conducting the reaction in the presence of CuOTf, 126, and hexafluoroisopropanol. ... 

Nitroalkenes are widely used in the eatalytie AFC alkylation of electron-rich aromatic rings such as indoles, pyrroles, electron-rich furans, and phenols. The literature up to 2009 dealing with catalytic AFC alkylation of aromatic compounds with nitroalkenes has been reviewed. In this section, only very recent progress on the development on catalytic AFC alkylation of nitroalkenes will be diseussed. 

This catalytie system exhibited a very good tolerance to water. In the presence of 2.5 mol% (5,5)-143 as catalyst in toluene/water (9 1 1 mL), the AFC alkylation of a variety of nitroalkenes with pyrroles afforded the alkylation products in up to 99% yield and 98% ee (Scheme 6.64). 

Scheme 6.70 CPA-catalyzed AFC alkylation of nitroalkenes with 4,7-dihydroin-doles and pyrroles reported by You.

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