Wolff-Kishner reduction limitations

The carbonyl reactivity of pyrrole-, furan-, thiophene- and selenophene-2- and -3-carbaldehydes is very similar to that of benzaldehyde. A quantitative study of the reaction of Af-methylpyrrole-2-carbaldehyde, furan-2-carbaldehyde and thiophene-2-carbaldehyde with hydroxide ions showed that the difference in reactivity between furan- and thiophene-2-carbaldehydes was small but that both of these aldehydes were considerably more reactive to hydroxide addition at the carbonyl carbon than A-methylpyrrole-2-carbaldehyde (76JOC1952). Pyrrole-2-aldehydes fail to undergo Cannizzaro and benzoin reactions, which is attributed to mesomerism involving the ring nitrogen (see 366). They yield 2-hydroxymethylpyrroles (by NaBH4 reduction) and 2-methylpyrroles (Wolff-Kishner reduction). The IR spectrum of the hydrochloride of 2-formylpyrrole indicates that protonation occurs mainly at the carbonyl oxygen atom and only to a limited extent at C-5. 

Alkylfurans are usually obtained by ring synthesis, decarboxylation of alkylfurancarboxy-lic acids, Wolff-Kishner reduction of aldehydes or ketones, or by reduction of halomethyl groups with zinc and acetic acid or LAH (79JOC3420) alkylation is of limited value. The chemistry of these compounds is conventional but oxidation to furancarboxylic acids cannot usually be carried out due to the lability of the ring. NBS bromination (Section 3.11.2.2.5) is a useful route to side-chain substituted compounds but reduction of esters to hydroxymethyl groups and subsequent transformation is often preferable. The haloalkyl compounds are extremely sensitive to resinification but if adequate precautions are taken they are... 

The combination of Friedel-Crafts acylation and Wolff-Kishner or Clemmensen reduction allows synthesis of alkylbenzenes free of the limitations of Friedel-Crafts alkylation. 

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