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

Authors

Nuwan Asanka Pannilawithana, Marquette University
Chae S. Yi, Marquette UniversityFollow

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 C_α–C_β 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 C_α–C_β 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 (C_α = 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

Accepted version. ACS Catalysis, Vol. 10, No. 10 (April 2020): 5852-5861. DOI. © 2020 American Chemical Society. Used with permission.

Recommended Citation

Pannilawithana, Nuwan Asanka and Yi, Chae S., "Catalytic Carbon–Carbon Bond Activation of Saturated and Unsaturated Carbonyl Compounds via Chelate-Assisted Coupling Reaction with Indoles" (2020). Chemistry Faculty Research and Publications. 1042.
https://epublications.marquette.edu/chem_fac/1042