Chemoselective α-Alkylation and α-Olefination of Arylacetonitriles with Alcohols via Iron-Catalyzed Borrowing Hydrogen and Dehydrogenative Coupling.

α-Alkyl and α-olefin nitriles are very important for organic synthesis and medicinal chemistry. However, different types of catalysts are employed to achieve either α-alkylation of nitriles by borrowing hydrogen or α-olefination by dehydrogenative coupling methods. Designing and developing high-performance earth-abundant catalysts that can procure different products from the same starting materials remain a great challenge. Herein, we report an iron(0) catalyst system that achieves chemoselectivity between borrowing hydrogen and dehydrogenative coupling protocols by simply changing the base. A broad range of nitriles and alcohols, including benzylic, linear aliphatic, cycloaliphatic, heterocyclic, and allylic alcohols, were selectively and efficiently converted to the corresponding products. Mechanistic studies reveal that the reaction mechanism proceeds through a dehydrogenative pathway. This iron catalytic protocol is environmentally benign and atom-efficient with the liberation of H2 and H2O as green byproducts.

Iron(0)-Catalyzed Transfer Hydrogenative Condensation of Nitroarenes with Alcohols: A Straightforward Approach to Benzoxazoles, Benzothiazoles, and Benzimidazoles.

The iron-catalyzed hydrogen transfer strategy has been applied to the redox condensation of o-hydroxynitrobenzene with alcohol, leading to the formation of benzoxazole derivatives. A wide range of 2-substituted benzoxazoles were synthesized in good to excellent yields without the addition of an external redox agent. A series of control experiments provided a plausible mechanism. Furthermore, the reaction system was successfully extended to the synthesis of benzothiazoles and benzimidazoles.

Direct Synthesis of Pyrrolo[1,2-α]quinoxalines via Iron-Catalyzed Transfer Hydrogenation between 1-(2-Nitrophenyl)pyrroles and Alcohols.

Herein, we describe novel iron-catalyzed transfer hydrogenation between alcohols and 1-(2-nitrophenyl)pyrroles for the synthesis of pyrrolo[1,2-α]quinoxalines. The tricarbonyl (η4-cyclopentadienone) iron complex catalyzed the oxidation of alcohols and the reduction of nitroarenes, and the corresponding aldehydes and aniline were generated in situ. The resulting Pictet-Spengler-type annulation/oxidation completed the quinoxaline structure formation. The protocol tolerated various kinds of functional groups and provided 29 samples of 4-substituted pyrrolo[1,2-α]quinoxalines. The developed method was also applied for the synthesis of additional polyheterocycles.

Iron-catalyzed one-pot synthesis of quinoxalines: transfer hydrogenative condensation of 2-nitroanilines with vicinal diols.

Here, we report iron-catalyzed one-pot synthesis of quinoxalines via transfer hydrogenative condensation of 2-nitroanilines with vicinal diols. The tricarbonyl (η4-cyclopentadienone) iron complex, which is well known as the Knölker complex, catalyzed the oxidation of alcohols and the reduction of nitroarenes, and the corresponding carbonyl and 1,2-diaminobenzene intermediates were generated in situ. Trimethylamine N-oxide was used to activate the iron complex. Various unsymmetrical and symmetrical vicinal diols were applied for transfer hydrogenation, resulting in quinoxaline derivatives in 49-98% yields. A plausible mechanism was proposed based on a series of control experiments. The major advantages of this protocol are that no external redox reagents or additional base is needed and that water is liberated as the sole byproduct.

Iron-Catalyzed Acceptorless Dehydrogenative Coupling of Alcohols With Aromatic Diamines: Selective Synthesis of 1,2-Disubstituted Benzimidazoles.

Benzimidazoles are important N-heteroaromatic compounds with various biological activities and pharmacological applications. Herein, we present the first iron-catalyzed selective synthesis of 1,2-disubstituted benzimidazoles via acceptorless dehydrogenative coupling of primary alcohols with aromatic diamines. The tricarbonyl (η4-cyclopentadienone) iron complex catalyzed dehydrogenative cyclization, releasing water and hydrogen gas as by-products. The earth abundance and low toxicity of iron metal enable the provision of an eco-friendly and efficient catalytic method for the synthesis of benzimidazoles.