Zinc Stabilized Azo-anion Radical in Dehydrogenative Synthesis of N-Heterocycles. An Exclusively Ligand Centered Redox Controlled Approach

Abstract

Herein we report an exclusively ligand-centered redox controlled approach for the dehydrogenation of a variety of N-heterocycles using a Zn­(II)-stabilized azo-anion radical complex as the catalyst. A simple, easy-to-prepare, and bench-stable Zn­(II)-complex (1b) featuring the tridentate arylazo pincer, 2-((4-chlorophenyl)­diazenyl)-1,10-phenanthroline, in the presence of zinc-dust, undergoes reduction to form the azo-anion radical species [1b]− which efficiently dehydrogenates various saturated N-heterocycles such as 1,2,3,4-tetrahydro-2-methylquinoline, 1,2,3,4-tetrahydro-isoquinoline, indoline, 2-phenyl-2,3-dihydro-1H-benzoimidazole, 2,3-dihydro-2-phenylquinazolin-4­(1H)-one, and 1,2,3,4-tetrahydro-2-phenylquinazolines, among others, under air. The catalyst has further been found to be compatible with the cascade synthesis of these N-heterocycles via dehydrogenative coupling of alcohols with other suitable coupling partners under air. Mechanistic investigation reveals that the dehydrogenation reactions proceed via a one-electron hydrogen atom transfer (HAT) pathway where the zinc-stabilized azo-anion radical ligand abstracts the hydrogen atom from the organic substrate(s), and the whole catalytic cycle proceeds via the exclusive involvement of the ligand-centered redox events where the zinc acts only as the template.

Zn(II)-Catalyzed Selective N-Alkylation of Amines with Alcohols Using Redox Noninnocent Azo-Aromatic Ligand as Electron and Hydrogen Reservoir

“…Control experiments revealed that the reaction begins with forming the single-electron reduced azo-anion radical species [ 1a ] − , which has been earlier identified in an analogous study . It is hypothesized that an alkoxide ligand forms an adduct with this radical anionic metal complex by simultaneously replacing the Cl – ligand to generate the catalytically active species, A , emphasizing the crucial role of the base t BuOK in facilitating deprotonation of the alcohol (Scheme ).…”

“… , To further ensure the hydrazo species, when 2j-D 2 was dehydrogenated stoichiometrically under optimized conditions, characteristic N–D stretching frequencies were observed at 2063 and 2116 cm –1 . , The deuterium labeling experiment confirms that the hydrogen/deuterium atoms removed during the dehydrogenation of 2j and 2j-D 2 are stored in the azo-chromophore. Analysis of the IR spectrum of the stoichiometric reaction of 1a , 3j , and 2j-D 2 , however, exhibits both N–H and N–D stretching at 3028, 3062 and 2085, 2113 cm –1 , respectively. , The ability of the electrochemically generated two-electron reduced hydrazo species [ 1a ] 2– to catalyze the conversion of benzophenone imine ( 6u′ ) to N -benzhydrylpyridin-2-amine ( 6u ) in the presence of 2j further confirms the active participation of the hydrazo species (see SI). Deuterium labeling experiment with 2-aminopyridine ( 3j ) and diphenylmethanol 2j-D 2 resulted in 25%-deuterium-incorporated N -alkylated amine product 6u-D (Scheme , entry 6).…”

One‐Pot Synthesis of Quinazolines via Elemental Sulfur‐Mediated Oxidative Condensation of Nitriles and 2‐(Aminomethyl)anilines

“…During the past decades, great progresses have been made for the synthesis of quinazoline derivatives (Scheme 1, a ). The traditional methods for such N ‐heterocycles are the condensation reactions of 2‐(aminomethyl)aniline and aldehydes/alcohols/nitriles in a combination of transition metal‐catalysts (such as Cu‐, Ni‐, Ir‐, Ru‐, Mn‐, and Zn‐complex) and oxidants [10–15] . Recently, quinazolines could be obtained efficiently under metal‐free conditions [16–21] .…”

“…The traditional methods for such Nheterocycles are the condensation reactions of 2-(aminomethyl)aniline and aldehydes/alcohols/nitriles in a combination of transition metal-catalysts (such as Cu-, Ni-, Ir-, Ru-, Mn-, and Zn-complex) and oxidants. [10][11][12][13][14][15] Recently, quinazolines could be obtained efficiently under metal-free conditions. [16][17][18][19][20][21] Further-more, the synthesis of corresponding quinazoline derivatives by organocatalytic protocols has been reported.…”

H2O2‐Promoted Inter‐ and Intramolecular C−N Bond Formation: Synthesis of Quinazoline Derivatives

“…[1] The CÀ N bond formation reaction and the direct synthesis of various nitrogen-containing heterocyclic compounds through the construction of CÀ N bonds have been fully studied and widely used in synthetic chemistry. [2] Since the 1960s, palladium, copper, iron and other transition metals [3][4][5][6][7][8][9][10][11] catalyzed the CÀ N bond coupling has become an important method for the synthesis of nitrogen heterocyclic compounds. With the continuous development of green synthesis, metalfree catalyzed CÀ N bond formation become the trend of modern synthesis.…”