Synthesis of α, β and γ-carbolines via Pd-mediated C_sp2-H/N–H activation

Abstract

An efficient method for the synthesis of halo-carbolines has been developed via Pd-catalysed formation of C–N bonds through Csp2-H/N–H activation of 4-methyl-N-[2-(pyridine-3-yl)phenyl] benzenesulfonamide derivatives.

Structural and Computational Investigation of Intramolecular N···H Interactions in α‐ and β‐Fluorinated 7‐Azaindoline Amides

“…The formation of N 7py ··· H α contacts is not limited to N 1 ‐acylated 7‐azaindolines, but extends to related heterocyclic scaffolds. For example, the acetyl protons of α‐carboline 15 are deshielded by 0.92 ppm compared with the corresponding carbazole (Table ) . The difference in the chemical shifts decreases to 0.25 ppm when the bromine is substituted by a methyl group…”

Synthesis Strategies for α‐, β‐, γ‐ and δ‐Carbolines

“…Since the Suzuki‐Miyaura‐mediated coupling reaction was successfully used in the synthesis of α‐carboline, this method was then explored to construct β‐carboline. As shown in Scheme 17A, the Suzuki‐Miyaura coupling reaction was successfully proceed to give compound 103 , and the Csp 2 ‐H/N−H bond of 101 was then activated under the oxidant Cu(OAc) 2 and catalyst Pd(OAc) 2 to afford halogenated β‐carboline ( 104 ) [31] . Similarly, biphenyl compound 107 was also generated by Suzuki‐Miyagi coupling, which was cyclized with aniline through further Buchwald‐Hartwiger reaction under the catalysis of palladium ligands to give the target β‐carboline 108 (Scheme 17B) [49] .…”

“…Therefore, palladium‐catalyzed cross‐coupling reaction between organic boron reagents and halogenated aromatics was further developed to afford carboline derivatives. For example, biaryl compound 51 was also obtained using this method, which was then converted to α‐carboline 52 and γ‐carboline 53 simultaneously through the formation of C−N bond with Cu(OAc) 2 as reductant and palladium as catalyst (Scheme 6B) [31] …”

“…For example, biaryl compound 51 was also obtained using this method, which was then converted to α-carboline 52 and γ-carboline 53 simultaneously through the formation of CÀ N bond with Cu(OAc) 2 as reductant and palladium as catalyst (Scheme 6B). [31] In addition, α-carboline was obtained through Stille coupling reaction catalyzed by palladium. [32] In this strategy, palladium-catalyzed cross-coupling was carried out between different pyridinium halides and aniline derivatives to form CÀ C bond, and then intramolecular cyclization of the intermediate bisaryl compounds was then promoted by a base to give αcarboline.…”

“…As shown in Scheme 17A, the Suzuki-Miyaura coupling reaction was successfully proceed to give compound 103, and the Csp 2 -H/NÀ H bond of 101 was then activated under the oxidant Cu(OAc) 2 and catalyst Pd(OAc) 2 to afford halogenated β-carboline (104). [31] Similarly, biphenyl compound 107 was also generated by Suzuki-Miyagi coupling, which was cyclized with aniline through further Buchwald-Hartwiger reaction under the catal- ysis of palladium ligands to give the target β-carboline 108 (Scheme 17B). [49] Moreover, one-pot addition-cyclization of nitrile 109 to substituted indole 110 was also developed to synthesize β-carboline 111 in the presence of Pd(OAc) 2 catalyst (Scheme 17C).…”