Science of Synthesis

Joule, J. A., Science of Synthesis Knowledge Updates, (2010) 2, 100.

The synthesis of pyrrole-ring-unsubstituted indoles by this strategy requires the generation of 2-(o-aminoaryl)acetaldehydes. A direct route to these is the oxidation of 2-(o-aminoaryl)ethanols, e.g. using bis(triphenylphosphine)ruthenium(II) chloride,[‌347‌] or catalytic dichloro(pentamethylcyclopentadienyl)iridium dimer [Ir(Cp*)Cl2]2 with potassium carbonate in refluxing toluene.[‌348‌] The 2-(o-aminoaryl)ethanols ‌395‌ are easily prepared via the base-catalyzed condensation of formaldehyde with the methyl group of 1-methyl-2-nitroarenes ‌392‌[‌347‌,‌349‌,‌350‌] followed by reduction of the nitro group. Remarkably, ring closure to indoles ‌394‌ can be brought about using either the precursor 2-(o-nitroaryl)ethanol ‌393‌ or the 2-(o-aminoaryl)ethanol ‌395‌. In the former case hydrogen, and a heterogeneous hydrogenation catalyst, rhodium/carbon, is included together with the homogenous ruthenium catalyst in the reaction mixture, and in the latter, hydrogen is evolved, quantitatively (‌Scheme 133‌).

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8-Meeeee-8M-eeeeee (‌888‌, M8 = Me; M8 = M8 = M); Meeeeee Meeeeeeee:[‌888‌]

M eeeeeee ee 8-eeeeee-8-eeeeee-8-eeeeeeeeeeee (88 e, 888 eeee), eeeeeeeeeeeeeeee (8.8 e, 88 eeee), eee 88% Meeeee M ee MeMM (8 eM) ee MMMM (88 eM) eee eeeeee ee 88°M eee 8 e. Mee eeeeeee eee eeeeeeeee eeee eee eeeeeee ee 88°M ee 8.8 Meee ee eeee 8-(8-eeeeee-8-eeeeeeeeeee)eeeeeee ee e eeeee-eeeeee eeeee; eeeee: 88.8 e (88% eeeee ee eeeeeeeeeeeeeeee).

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M eeeeeee ee 8-(8-eeeee-8-eeeeeeeeeeee)eeeeeee (8.8 e, 8.8 eeee) eee MeMe8(MMe8)8 (8.88 eeee) ee eeeeeee (88 eM) eeeee eeeee eee eeeeee ee eeeeee eee 8 e. Meeeee eeeeee eeee eee eeeeeee; eeeee: 8.88 e (88%).

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References