Alkene Isomerization-Hydroarylation Tandem Catalysis: Indole C2-Alkylation with Aryl-Substituted Alkenes Leading to 1,1-Diarylalkanes

• Published in: Chemistry, an Asian journal an Asian journal, 2014-05, Vol.9 (5), p.1242-1246
• Main Authors: Yamakawa, Takeshi, Yoshikai, Naohiko
• Format: Article
• Language: English
• Subjects: alkenes; alkylation; Catalysis; Chemistry; cobalt; CH functionalization; indoles
• ISSN: 1861-4728; 1861-471X
• DOI: 10.1002/asia.201400135

A cobalt‐N‐heterocyclic carbene catalyst generated from CoBr2, imidazolium salt, and cyclohexylmagnesium bromide was found to promote the imine‐directed C2‐alkylation of indoles with nonconjugated arylalkenes through a tandem alkene isomerization–hydroarylation process, affording 1,1‐diarylalkanes with exclusive regioselectivity. The feasibility of the tandem catalysis was demonstrated for allyl‐, homoallyl‐, and bishomoallylbenzene derivatives. The catalytic system is also applicable to a variety of β‐substituted styrene derivatives. Mechanistic experiments using deuterium‐labeled indole substrate and Grignard reagent provided insight into the cobalt‐mediated CH activation step, which likely involves exchange of the C2‐hydrogen atom of the former and the β‐hydrogen atoms of the latter. …︁ but that′s secondary: A catalytic system consisting of CoBr2, N‐heterocyclic carbene, and cyclohexylmagnesium bromide promotes the imine‐directed addition of indoles to nonconjugated aryl‐substituted alkenes through tandem alkene isomerization–hydroarylation, affording 1,1‐diarylalkane derivatives with exclusive regioselectivity. Deuterium‐labeling experiments revealed the involvement of the secondary alkyl Grignard reagent in the cobalt‐mediated CH activation process.