Indoles ruthenium-catalysis

Stephenson and coworkers applied reductive photoredox catalysis to trigger radical 6-exo cyclizations of co-pyrrole or co-indole-substituted a-bromocarbonyl compounds 124 [186] as well as radical 5-exo cyclizations of 2-bromo-2-(4-pentenyl)malonates 126 (Fig. 32) [187]. These cyclization processes provide bi- or tricyclic products 125 or cyclopentanecarboxylates 127 in moderate to excellent yields. The initial radical was formed with reduced ruthenium catalyst HOB generated similarly as above from 110 and a sacrificial amine... 

The same differential behavior can be observed with amine nucleophiles. For example, calcium triflate promotes the aminolysis of propene oxide 84 with benzylamine to give 1-(A -benzyl)amino-2-propanol 85, the result of attack at the less substituted site <03T2435>, and which is also seen in the solventless reaction of epoxides with heterocyclic amines under the catalysis of ytterbium(III) triflate <03SC2989>. Conversely, zinc chloride directs the attack of aniline on styrene oxide 34 at the more substituted carbon center <03TL6026>. A ruthenium catalyst in the presence of tin chloride also results in an SNl-type substitution behavior with aniline derivatives (e.g., 88), but further provides for subsequent cyclization of the intermediate amino alcohol, thus representing an interesting synthesis of 2-substituted indoles (e.g., 89) <03TL2975>. 

Borylated pyrrole 88 was prepared by Oestreich by treatment of the corresponding pyrrole with pinacolborane and a ruthenium(II) thiolate complex. The direct synthesis of 88 promises to find wide utility in medicinal chemistry and was applied to a variety of substituted indoles (13JA10978). N-Methylpyrrole was directly arylated at room temperature by photoredox catalysis with diaryliodonium salts to furnish 89 in 84% yield (13SL507). 

On the other hand, several groups have also recently developed asymmetric domino reactions through relay catalysis with combinations of organocatalysts with ruthenium catalysts. For example. You et al. demonstrated in 2009 that ruthenium catalyst could be compatible with Bronsted acid catalyst. They reported a practical and economical synthesis of chiral tetrahydropyrano[3,4-b]indols and tetrahydro-p-carbolines by the combination of ruthenium-catalysed olefin cross-metathesis and a chiral phosphoric acid-catalysed Friedel-Crafts alleviation reaction, as shown in Scheme 7.41. This domino reaction allowed the use of readily available materials to highly enantioselectively construct synthetically valuable polycyclic indole frameworks in enantioselectivity of up to 94% ee. 

Later, You et al. investigated relay catalysis consisting of a combination of the same ruthenium catalyst and a closely related chiral BINOL-derived phosphoric acid. As shown in Scheme 7.42, the use of this catalyst system in an asymmetric domino intramolecular Friedel-Crafts-type-aza-Michael reaction allowed a range of chiral fused indoles to be achieved in high yields and moderate to high enantioselectivities from the corresponding enones and indolyl olefins. 

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