Nickel-catalyzed C–H alkylation of indoles with unactivated alkyl chlorides: evidence of a Ni(i)/Ni(iii) pathway

Abstract

A mild and efficient nickel-catalyzed method for the chemo and regioselective coupling of unactivated alkyl chlorides with the C–H bond of indoles and pyrroles at 60 °C is described.

Nickel-catalyzed and Li-mediated regiospecific C–H arylation of benzothiophenes

“…Similarly to previous studies on Pd 36 and Ni-catalyzed C-H arylation reactions, 30,32,37 lithium seems to be a key element for the reactivity of this benzothiophene-nickel system. The unique role of LiHMDS is not solely due to its capacity to generate the lithiated benzothiophene (BT-Li) in solution.…”

Recent Advances in Metal‐Catalyzed Functionalization of Indoles

“…The Punji group also developed a related Ni(I)‐catalyzed C2−H alkylation of indoles through the coupling of alkyl chlorides with the N‐2‐pyridinyl‐indoles (Scheme 21). [39] The most active catalyst system consisted of (thf) 2 NiBr 2 (5 mol%) in the presence of bpy (5 mol%), while interestingly (bpy)NiBr 2 gave slightly lower yields. The reactions were carried using LiHMDS as a base in toluene at mild temperature of 60 °C.…”

“… Nickel‐catalyzed C2−H alkylation of indoles by Punji [39] …”

C−H Functionalization of Indoles by 3d Transition‐Metal Catalysis

“…This protocol allowed the coupling of indoles with various unactivated primary and secondary alkyl halides with very broad substrates scope that includes the tolerance of nitriles, ethers, alkenes and halides. Following this report, the same group developed a mild and efficient protocol for chemo and regioselective alkylation of indoles using challenging and unactivated alkyl chlorides . Notably, the use of LiHMDS base helped this protocol to perform at relatively mild reaction conditions.…”