Title

Catalytic Carbon–Carbon Bond Activation of Saturated and Unsaturated Carbonyl Compounds via Chelate-Assisted Coupling Reaction with Indoles

Document Type

Article

Publication Date

4-2020

Publisher

American Chemical Society

Source Publication

ACS Catalysis

Source ISSN

2155-5435

Original Item ID

DOI: 10.1021/acscatal.0c01245

Abstract

The chelate assistance strategy was devised to promote a highly regioselective catalytic C–C bond activation reaction of saturated and unsaturated carbonyl compounds. The cationic Ru–H complex 1 was found to be an effective catalyst for mediating the coupling reaction of 1,2-disubstituted indoles with α,β-unsaturated aldehydes and ketones, in which the regioselective Cα–Cβ activation of the carbonyl substrates has been achieved in forming the 3-alkylindole products. The analogous coupling reaction of indoles with saturated aldehydes and ketones directly led to the Cα–Cβ cleavage of the carbonyl substrates in forming the 3-alkylindole products. The coupling reaction of 1,2-dimethylinole with (E)-3-nonen-2-one and 2-propanol-d8 showed 20–22% of deuterium incorporation to both α- and β-CH2 of the 3-alkylindole product. The coupling reaction of 1,2-dimethylinole with (E)-3-nonen-2-one exhibited the most significant carbon kinetic isotope effect on the α-carbon of the product (Cα = 1.046). The Hammett plot constructed from the reaction of 1,2-dimethylinole with a series of para-substituted enones p-X-C6H4CH═CHCOCH3 (X = OMe, Me, H, Cl, CF3) showed a modest promotional effect by an electron-donating group (ρ = −0.2 ± 0.1). Several catalytically relevant Ru–H species were detected by NMR from a stoichiometric reaction mixture of the Ru–H complex 1 with 1,2-dimethylindole and (E)-3-nonen-2-one in CD2Cl2. These results support a mechanism of the catalytic coupling reaction via conjugate addition of indoles to enones followed by the C–C bond activation and hydrogenolysis steps.

Comments

ACS Catalysis, Vol. 10, No. 10 (April 2020): 5852-5861. DOI.

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