A straightforward and atom-economical method is described for the synthesis of 2,3-disubstituted indoles. Anilines and 1,2-diols are condensed under neat conditions with catalytic amounts of either [Cp*IrCl(2)](2)/MsOH or RuCl(3)·xH(2)O/phosphine (phosphine = PPh(3) or xantphos). The reaction does not require any stoichiometric additives and only produces water and dihydrogen as byproducts. Anilines containing methyl, methoxy, chloro and fluoro substituents can participate in the cyclocondensation. Meta-substituted anilines give good regioselectivity for 6-substituted indoles, while unsymmetrical diols afford excellent regioselectivity for the indole isomer with an aryl or large alkyl group in the 2-position. The mechanism for the cyclocondensation presumably involves initial formation of the α-hydroxyketone from the diol. The ketone subsequently reacts with aniline to generate the α-hydroxyimine which rearranges to the corresponding α-aminoketone. Acid- or metal-catalysed electrophilic ring-closure with the release of water then furnishes the indole product.
A straightforward procedure is described for the synthesis of piperazines from amines and 1,2‐diols. The heterocyclization is catalyzed by [Cp*IrCl2]2 and sodium hydrogen carbonate and can be achieved with either toluene or water as solvent. The transformation does not require any stoichiometric additives and only produces water as the byproduct. The reaction can be performed between a 1,2‐diamine and a 1,2‐diol or by a double condensation between a primary alkylamine and a 1,2‐diol. At least one substituent is required on the piperazine ring to achieve the cyclization in good yield. The mechanism is believed to involve dehydrogenation of the 1,2‐diol to the α‐hydroxy aldehyde, which condenses with the amine to form the α‐hydroxy imine. The latter rearranges to the corresponding α‐amino carbonyl compound, which then reacts with another amine followed by reduction of the resulting imine.
A versatile procedure for the synthesis of optically pure 1-amino-3-aryl indanes is presented, exemplified by the synthesis of the triple uptake inhibitor (+)-indatraline (1).
The title reaction is achieved under neat conditions with either an iridium or a ruthenium catalyst and with water and hydrogen gas as the only stoichiometric by-products. For unsymmetric diols excellent regioselectivity is obtained for the indole isomer with a large substituent in the 2-position. -(TURSKY, M.; LORENTZ-PETERSEN, L. L. R.; OLSEN, L. B.; MADSEN*, R.; Org. Biomol. Chem. 8 (2010) 24, 5576-5582, http://dx.doi.org/10.1039/c0ob00106f ; Dep. Chem., Tech. Univ. Den., DK-2800 Lyngby, Den.; Eng.) -Bartels 17-121
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