C−N Cross‐Coupling Reactions Under Mild Conditions Using Singlet Di‐Radical Nickel(II)‐Complexes as Catalyst: N‐Arylation and Quinazoline Synthesis

Abstract

Herein we report a cost-effective synthetic approach for CÀ N cross-coupling reactions of a broad array of nitrogen nucleophiles and aryl halides under mild conditions. These reactions are catalyzed by an inexpensive, air-stable, earth-abundant and easy-to-prepare singlet di-radical nickel(II)-catalyst containing two antiferromagnetically coupled single-electron oxidized diiminosemiquinonato type ligands. This protocol provides an alternative method for CÀ N cross-coupling reactions avoiding nickel(0)/nickel(II) or nickel(I)/ nickel(III) redox processes via cooperative participation of metal and ligand-centered redox events. Besides a wide range of N-arylation reactions, by judicious choice of aryl halides and nitrogen nucleophiles the synthesis of a variety of polysubstituted quinazolines has been achieved in moderate to good yields under relatively mild reaction conditions. Our catalyst has been found to be almost equally effective in quinazoline synthesis via CÀ N cross-coupling of (i) 2-bromobenzylamine with benzamide, and (ii) 2-bromobenzylbromide with amidine. Control experiments and DFT studies were performed to improve the understanding of the cooperative participation of ligand and metal (nickel)-centered redox events during oxidative addition/reductive elimination processes of the catalytic cycle and to shed light on the plausible mechanistic pathway of the CÀ N crosscoupling reactions.

Dehydrogenative Azolation of Arenes in a Microflow Electrochemical Reactor

“…The reaction mixture was purified by flash chromatography on silica (cyclohexane to cyclohexane/ethyl acetate 97:3) to give a yellowish oil (12 mg, 44%, A / B 4:1). The analytical data correspond to the reported ones in literature . Compound 7A 1 H NMR (400 MHz, CDCl 3 ): δ 8.03 (d, J = 2.4 Hz, 1H), 7.72 (m, 2H), 7.30 (td, J = 7.9, 1.7 Hz, 1H), 7.06–7.03 (m, 2H), 6.43 (t, J = 2.1 Hz, 1H), 3.88 (s, 3H).…”

“…The analytical data correspond to the reported ones in literature. 72 Compound 7A 1 H NMR (400 MHz, CDCl 3 ): δ 8.03 (d, J = 2.4 Hz, 1H), 7.72 (m, 2H), 7.30 (td, J = 7.9, 1.7 Hz, 1H), 7.06–7.03 (m, 2H), 6.43 (t, J = 2.1 Hz, 1H), 3.88 (s, 3H). 13 C{ 1 H} NMR (101 MHz, CDCl 3 , mixture of A and B ): δ 158.3, 151.4, 140.7, 140.2, 131.7, 129.9, 128.1, 126.9, 125.4, 121.3, 121.0, 114.6, 112.4, 107.3, 106.3, 56.1, 55.7.…”

Nickel‐Catalyzed Synthesis of Pyrimidines via Dehydrogenative Functionalization of Alcohols

“…For catalyst 1 a inert condition and slightly higher temperature is required to get the products in satisfactory yields while the catalyst 2 a affords the respective pyrimidines in even higher yields under comparatively mild aerobic conditions. Moreover, the metal‐ligand cooperativity and active involvement of ligand centered radical in 2 a allow to achieve pyrimidines in good yields even starting from unactivated alcohols bearing strongly electron‐withdrawing substituents. Overall, the metal‐ligand cooperative approach via active involvement of the ligand centered redox process during catalysis allow to avoid the energetically demanding high energy nickel centered redox processes and allow to achieve the reactions under mild and aerobic conditions.…”

In Silico and Biological Evaluation of N‐(2‐methoxyphenyl) Substituted Pyrazoles Accessed via a Sonochemical Method

“… [4,8,12] However, since a limited number of arylhydrazines are commercially available hence these methods often involve the complicated and multi‐step preparation of necessary hydrazines and sometimes the other starting compounds. During the last decade, significant progress has been made in the area of transition metal catalyzed formation of aryl C−N bonds and their applications in the general synthesis of bioactive molecules or compounds of pharmacological importance [19,20] . Accordingly, CuI‐catalyzed N ‐arylation of various nitrogen containing heterocycles including pyrazoles with aryl and heteroaryl halides have been reported (Method B, Scheme 1).…”

“…During the last decade, significant progress has been made in the area of transition metal catalyzed formation of aryl CÀ N bonds and their applications in the general synthesis of bioactive molecules or compounds of pharmacological importance. [19,20] Accordingly, CuI-catalyzed N-arylation of various nitrogen containing heterocycles including pyrazoles with aryl and heteroaryl halides have been reported (Method B, Scheme 1). [21][22][23][24] Indeed, the scope and usefulness of these methods have been demonstrated by synthesizing a variety of N-aryl pyrazoles.…”