Cobalt‐Catalyzed Oxidative Dimerization of 2‐Phenylpyridine Derivatives

Abstract

The oxidative dimerizationo f2 -phenylpyridine derivatives using cobalt catalysis is reported. Three types of reaction conditions were developed with different loadings of cobalt catalyst. Cross couplingo ft wo different 2arylpyridines using cobalt catalysis proceeded with modest yields and selectivity.The biaryl moiety is one of the most important privileged structures in medicinal chemistry and is prevalent in al arge number of pharmaceuticals and biologically active molecules. [1] Many methods have been developedt op repare aryl-aryl or aryl-heteroaryl compounds. In this transformation, at ransitionmetal catalyzedc ross-coupling reactiono ft wo prefunctionalized materials has been well documented. [1] The low valent cobalt complexes, usually in situ generated, exhibit high reactivity and selectivity in the cross-coupling reaction. [2] Recently, transition-metal-catalyzed homocoupling of CÀH/CÀHb onds has been developeda sa ne fficient and straightforward strategy for constructing biaryl skeletons. [3] This approach does not requirep refunctionalized startingm aterials, which reduces the synthetic steps and amount of byproducts. 2-Arylpyridines, phenylacetamides, anda ryloxazolines were proven to be effective substrates to undergo the oxidative homocoupling reaction for construction of the biaryl compounds using Pd, [4] Ru, [5] and Ni [6] catalysis. Yu and co-workersreported Cu II -mediated dimerization of 2-arylpyridines. [7] The research group of Daugulis described the Co III -promoted dimerization of aminoquinoline benzamides. [8] However,i nt heset wo cases, either Cu or Co salt was stoichiometrically required. Herein, we report the oxidative homocoupling of 2-phenylpyridinesw ith am ore abundant and cheaper cobalt catalyst using PhI(OAc) 2 and O 2 as cooxidants.During our recent studies on cobalt-mediated ortho-CÀH functionalization of carboxamide 1,w eo bserved the formation of dimerization product 2 and isolated two types of cobaltamide complexes 3 and 4 [9] [Eq. (1)].X -ray single-crystald iffraction established the structurest ob eb iaryl-linked diamide compounds complexed with Co III metal anda na cetylacetone anion as the ligand. The difference between co-amide complexes 3 and 4 is the different orientation of the acetylacetone anion group that is attached to the cobalt metal. Prior to our optimization of the reaction conditions for this reaction, the research group of Daugulis [8] publishedt heir study on the same reaction. Therefore, we focused our attention on the dimerization of other types of substrates using cobalt catalysis. As 2phenylpyridines werew ell used as substrates in the cobalt-catalyzed coupling reaction, [10] we envisionedt hat 2-phenylpyridines could undergo an oxidativeh omocoupling reaction via cobalt catalysis under the appropriate conditions.The investigation of the oxidative homocoupling reaction employed 2-phenylpyridine 5a as the substrate. The initial reactions conditions included Co(OAc) 2 ·4 H 2 O( 10 mol %) and PhI(OAc) 2 (2 equiv) as an oxidanti nA cOH under reflux, ...

Mechanistic details of the cobalt-mediated dehydrogenative dimerization of aminoquinoline-directed benzamides

“…We also wish to mention previous example of this type of complex reported by Xie et al in 2016. 15 In this report Xie et al were able to isolate a structure with the biaryl coupling and acetylacetanoate in the 5 th and 6 th coordination spheres.…”

“…Complex 4 adds to the small number of isolable Co(III)-aryl complexes prepared via direct C-H insertion. 15,29,[32][33][34] Inspired by these experimental ndings, we extended our computational studies to explore the reactivity of [Co(BQN) 2 (PivO)], 1a. We found that this complex possesses a trigonal bipyramid geometry (see Fig.…”

“…Recent research by several groups has led to the discovery of multiple cobalt and copper promoted aryl-aryl and aryl-heteroaryl dimerization reactions. [13][14][15][16][17] Scheme 1a highlights a recent example of the Comediated homocoupling of aminoquinoline (AQ) benzamides. 16 In light of these synthetic advances, the key mechanistic features of the rst-row transition metal mediated dehydrogenative coupling of AQ benzamides warrants comprehensive Scheme 1 Representative of the cobalt-mediated dehydrogenative dimerization of aminoquinoline benzamide derivatives.…”

Mixed Directing‐Group Strategy: Oxidative C−H/C−H Bond Arylation of Unactivated Arenes by Cobalt Catalysis

“…[5] Over the past decade,i nsitu generated low-valent cobalt catalysts have been utilized in C À H arylation of arenes with aryl Grignard reagents,a ryl halides, and phenol derivatives in the presence of Grignard reagents as the bases and reductants. [7] In contrast, the bidentate directing strategy using the relatively cheap Cp*-free (Cp* = C 5 Me 5 )C oX n (n = 2, 3) salts as catalysts has become apromising methodology for C À Hb ond functionalization. [7] In contrast, the bidentate directing strategy using the relatively cheap Cp*-free (Cp* = C 5 Me 5 )C oX n (n = 2, 3) salts as catalysts has become apromising methodology for C À Hb ond functionalization.…”

Mixed Directing‐Group Strategy: Oxidative C−H/C−H Bond Arylation of Unactivated Arenes by Cobalt Catalysis

“…[6] However,t ot he best of our knowledge,n oc obalt-catalyzed cross-coupling reaction between two aryl CÀHb onds has been developed so far. [7] In contrast, the bidentate directing strategy using the relatively cheap Cp*-free (Cp* = C 5 Me 5 )C oX n (n = 2, 3) salts as catalysts has become apromising methodology for C À Hb ond functionalization. [8] Recently,c obalt-catalyzed C(sp 2 ) À Hamination and alkoxylation, assisted by abidentate directing group,w as described by our group.…”