Ruthenium(II)‐ or Rhodium(III)‐Catalyzed Grignard‐Type Addition of Indolines and Indoles to Activated Carbonyl Compounds

Abstract

The ruthenium(II)‐ or rhodium(III)‐catalyzed pyrimidinyl‐directed Grignard‐type C−H additions of N‐heterocycles with activated aldehydes and ketones are described. A cationic ruthenium catalyst and sodium acetate additive in dichloroethane as solvent were found to be optimal catalytic system for the construction of C‐7 alkylated indolines. In sharp contrast, a cationic rhodium complex allows the generation of C‐2 alkylated indoles and pyrroles as well as C‐1 alkylated carbazoles. The site‐selective C−H functionalization of these heterocyclic scaffolds could be an important asset towards the development of novel bioactive compounds.magnified image

Transition-Metal-Catalyzed C–H Bond Addition to Carbonyls, Imines, and Related Polarized π Bonds

“…13 The alcohol products were obtained in good yield when electron-rich groups or halogen substituents were placed around the aromatic portion of the indoline ring. The reaction also tolerated alkyl and aryl functionality at the C2 and C3 positions.…”

“…13 The indole heterocycle class was the most extensively evaluated, and functionalization selectively occurred at the C2 position. A range of electron-rich and electron-poor functionality was compatible at the C3–C7 positions, and the alcohol products were obtained in high yield.…”

Transition‐Metal‐Catalyzed C−H Functionalization for Construction of Quaternary Carbon Centers

“…By using a pyrimidine as an directing group, the Kim laboratory has recently demonstrated that heterocycles of indolines, indoles, pyrroles, and carbazoles underwent site‐selective C−H bond addition to trifluoropyruvates under rhodium catalysis to provide the corresponding tertiary alcohols 177 in good yields (Scheme ). It is noteworthy that indolines favor the C−H functionalization at C7 position, while indoles are selectively functionalized at C2 position.…”

Rhodium(I)‐Catalyzed C2‐Selective Decarbonylative C−H Alkylation of Indoles with Alkyl Carboxylic Acids and Anhydrides

“…Meanwhile, the groups of Bach, [5a,c,e] Ackermann, [5b,d,f] Punji [5g,i,j] and Shi [5h] have independently developed C2−H alkylation of indoles with alkyl halides using Pd, Ni, Co and Mn catalysts. Such a transformation has also been successfully implemented by using 2‐vinyloxiranes, [6a] alkyltrifluoroborates, [6b,h,i] diazo compounds, [6c,g] alkylarenes, [6d,j] cyclopropanols, [6e] carbonyl compounds, [6f] imines [6k] and acetonitrile derivatives [6l] . Despite the impressive progress made so far, the development of new and efficient strategies to access C2‐alkylated indoles with readily available alkylation reagents is still highly desirable.…”