Addition of Indolines and Indoles to Carbonyls

  • Author: ChemistryViews.org
  • Published: 06 August 2016
  • Copyright: Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
  • Source / Publisher: Advanced Synthesis & Catalysis/Wiley-VCH
thumbnail image: Addition of Indolines and Indoles to Carbonyls

Substituted indolines and indoles are common frameworks in pharmaceutical chemistry. Grignard-type additions of carbonyl compounds are an atom-economical way to introduce substituents to these heterocycles, especially at the C-7 position. A site-selective way of alkylating indoles and indolines using such reactions would be a useful addition to the organic chemist's toolbox.


In Su Kim, Sungkyunkwan University, Suwon, Republic of Korea, and colleagues have developed such a site-selective Grignard-type C–H addition protocol for coupling N-heterocycles with activated aldehydes and ketones. The team used a ruthenium catalyst to synthesize C-7 alkylated indolines and a rhodium complex to prepare C-2 alkylated indoles (substitution sites pictured).


The team used [Ru(p-cymene)Cl2]2 and AgSbF6 together with sodium acetate to generate the active catalyst. With this approach, they were able to couple a large variety of indolines at the C-7 position to activated carbonyl compounds in dichloroethane solution. A pyrimidyl group on the heterocycle was used as a directing group. Similarly, a catalyst based on [RhCp*Cl2]2, AgSbF6, and NaOAc was used to alkylate a range of pyrimidyl-substituted indoles at C-2 in good to excellent yields. According to the researchers, this work expands the scope of catalytic Grignard-type additions and could be used to generate the scaffolds of biologically active compounds.


 

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