Palladium‐Catalyzed Selective Synthesis of Dibenzo[c,e]azepin‐5‐ols and Benzo[c]pyrido[2,3‐e]azepin‐5‐ols

Abstract

An efficient palladium‐catalyzed tandem addition/cyclization of 2′‐formyl‐[1,1′‐biaryl]‐2‐carbonitriles with arylboronic acids is reported. This reaction affords dibenzo[c,e]azepin‐5‐ols and benzo[c]pyrido[2,3‐e]azepin‐5‐ols with excellent selectivity and wide functional group compatibility. The dibenzo[c,e]azepin‐5‐ols show good cell growth inhibitory activity against a triple‐negative breast cancer cell line. Moreover, the proposed mechanistic rationale for this tandem process is supported by theoretical calculations.magnified image

Palladium-Catalyzed Cascade Reactions of 2-(Cyanomethoxy)chalcones with Arylboronic Acids: Selective Synthesis of Emissive Benzofuro[2,3-c]pyridines

“…This has evoked a new series of explorations concerning the carbopalladation of nitriles, with the potential to synthesize structurally diverse five- or six-membered N -heterocycles, as demonstrated by our own group and others (Scheme b). Very recently, our group reported the palladium-catalyzed cascade reactions of 2′-acetyl-[1,1′-biphenyl]-2-carbonitriles with arylboronic acids for the synthesis of seven-membered 5 H -dibenzo­[ c , e ]­azepines . However, the selective reaction of cyano-substituted chalcones with arylboronic acids is still a significant challenge, because the carbopalladation of nitriles competes with the conjugate addition of arylboronic acids to α,β-unsaturated carbonyl compounds.…”

Metal-catalyzed reactions of organic nitriles and boronic acids to access diverse functionality

“…60 In this context in 2019, Chen, Xia and co-workers developed a Pd(II)-catalyzed cascade reaction of 2′-acetyl-[1,1′-biphenyl]-2-carbonitriles ( 80) with arylboronic acids for the construction of a seven-membered 5-arylidene-7-aryl-5H-dibenzo [c,e] In the same year ( 2019), the synthesis of dibenzo [c,e]azepin-5-ols and benzo [c]pyrido[2,3-e]azepin-5-ols ( 83) was developed via a Pd(II)-catalyzed tandem addition and cyclization of 2′formyl-[1,1′-biaryl]-2-carbonitriles ( 82) with arylboronic acids by Chen's group (Scheme 40). 62 The synthesized dibenz [c,e] azepin-5-ols showed a good cell-growth-inhibitory activity against a triple-negative breast cancer cell line. Both these substrates with EDGs and the EWGs are compatible with this transformation and provided the desired products in moderate to high yields.…”

Synthesis of N-Heterocycles via Transition-Metal-Catalyzed Tandem Addition/Cyclization of a Nitrile

“…Proposed mechanism for the Pd-catalyzed threecomponent tandem process Very recently, Chen's group reported another tandem addition/cyclization to form the seven-membered N-heterocyclic dibenzoazepines (Scheme 32). 41,42 Derivatives of azepine have been found to possess different bioactivities. However, only limited methods disclosing their synthesis have been reported to date.…”