Furans, carbon atom reactivity with

Both uncatalyzed and catalyzed [4+2]-cycloaddition reactions of furans with the allenic esters have been reported (Table 12.6) [93]. The allene adds from the less hindered C1-C2 Jt-face. The unfavorable steric interaction between the a-hydrogen atom of the furan and the methyl group at C4 of the allene is responsible for this selectivity. The more reactive 2-methylfuran adds to the allenic ester also in a regio-selective manner. The C2 carbon atom of 2-methylfuran was exclusively attached to the Cl carbon atom of the allenic ester, providing a mixture of endo- and exoadducts. 

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. 

Installation of the furan ring requires two extra carbons provided by a Sonagashira coupling with trimethylsilyl acetylene to give 39. Cu (I)-catalysed closure of the furan ring follows and now the role of the chlorine atom on the pyridine ring is revealed. It is there to block the most reactive position and, its job complete, it can now be removed by hydrogenation. 

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