A Copper‐Catalyzed Cascade Approach for the Synthesis of Dibenzo[b,f]1,8‐naphthyridine Derivatives

Abstract

The synthesis of some dibenzo[b,f]‐[1,8]naphthyridine derivatives in a cascade manner is reported. The reaction includes a Knovenagel condensation, the insertion of a nitrile and an alkyne into an N–H bond and an oxidation/oxidative C–C bond cleavage sequence in the presence of copper iodide. The key 1,8‐naphthyridine core was constructed in a cascade manner during the course of the reaction itself which allows diverse dibenzo[b,f]‐[1,8]naphthyridine derivatives to be readily prepared.magnified image

Copper-Catalyzed Cascade Synthesis of 2-Aryl-3-cyanobenzofuran and Dibenzo[b,f]oxepine-10-carbonitrile Derivatives

“…In a continuation of our research efforts in exploring additional synthetic aspects of 2-iodobezylcyanide surrogates for the construction of various valuable heterocyles and based on clues provided in literature cited above (Scheme , eqs 1–3), we hypothesized that it might be possible to prepare 2-aryl-3-cyanobenzofuran derivatives through the in situ generation of the hydroxyl intermediate III from iodoarene, using 2-iodobenzylcyanides 2a and benzaldehyde 1a as starting materials (Scheme , eq 4). This might be achieved through Knoevenagel condensation, aryl hydroxylation, oxa-Michael addition, and aromatization reactions in a cascade manner by utilizing some previously reported copper-mediating protocols .…”

Sequential Addition of Amines to Nitrile and Carbon–Carbon Multiple Bond: A Route to 7-Amino-5H-dibenzo[c,e]azepines

“…Demir et al reported that Ph 3 PAuCl and Zn­(ClO 4 ) 2 cooperatively catalyzed tandem hydroamination/cyclization reaction of electron-deficient cyanoalkynes with amines to give 2-aminopyrroles as the main products with a different cyclization pattern (Scheme c) . Yao et al described the construction of 1,8-naphthyridine core through a sequential intramolecular insertion of a nitrile and an alkyne into an N–H bond of amides in the presence of CuI and base (Scheme d) …”

“…Replacement of Y­[N­(SiMe 3 ) 2 ] 3 with other rare-earth-metal sources, such as Y­(OTf) 3 or YCl 3 , resulted in no reaction (entries 15 and 16). In addition, CuI showed no catalytic activity even in the presence of base (entry 17) …”

“…8 Yao et al described the construction of 1,8-naphthyridine core through a sequential intramolecular insertion of a nitrile and an alkyne into an N−H bond of amides in the presence of CuI and base (Scheme 1d). 9 Despite significant advances in this area, these transformations are currently limited to the formation of fiveand six-membered azaheterocycles. The construction of the entropi- cally unfavorable larger N-containing heterocycles through tandem hydroamination/cyclization of cyanoalkynes with amines or reaction of nitriles with aminoalkynes has not yet to be accomplished.…”

“…In addition, CuI showed no catalytic activity even in the presence of base (entry 17). 9 Having the optimized conditions in hand, we continued to test the generality of this method. As depicted in Scheme 2, aliphatic secondary amines 2a−2j were appropriate substrates, the corresponding (E)-7-amino-5-benzylidene-5H-dibenz[c,e]azepines 3aa−3aj were obtained in 65−86% yields.…”