Direct Transformation of Nitroalkanes to Nitriles Enabled by Visible-Light Photoredox Catalysis and a Domino Reaction Process

Abstract

A mild and convenient process for direct transformation of nitroalkanes to the corresponding nitriles was developed using a visible-light photoredox catalysis strategy with household decorative blue LEDs and the additives of Et3N and DIPIBA (or DIPEA). Application of the process in secondary nitroalkanes bearing a β-alcohol resulted in a domino process of the retro-Henry reaction and the subsequent acetalization, aldol, cyanohydrin, and ring-contraction reactions with stereoselectivities. The photocatalytic reaction was demonstrated by a continuous flow method.

A mild one-pot transformation of nitroalkanes to ketones or aldehydes via a visible-light photocatalysis–hydrolysis sequence

“…We performed the reaction of 1a with Ru(bpy) 3 Cl 2 •6H 2 O, DIPEA, and Mg(ClO 4 ) 2 in CH 3 CN under blue LED irradiation for 2 h, as described in the literature method for producing the oxime from the primary nitroalkane by visible-light photoredox catalysis. 12 However, only 28% of the oxime product 2a was obtained, along with 66% yield of nitrone 3a (Table 1, entry 1). Since we discovered that adding Et 3 N (10 equiv.)…”

“…Although catalyst II and catalyst III both showed superior and comparable results in this reaction, we chose catalyst II for further optimization due to its lower commercial cost and convenient preparation process. 18 With catalyst II, we examined several reaction concentrations, ranging from 0.05 M to 0.2 M, and the 0.1 M condition gave the best results (Table 1, entries [12][13][14][15]. Lowering the catalyst loading from 2 mol% to 1 mol% increased the yield to 80%, but decreasing the catalyst loading to 0.5 mol% reduced the yield to 74% (Table 1, entries 16 and 17).…”

“…Conducting the reaction under the same conditions but with a higher concentration did not increase the yield and the best yield of 4a (76%) was obtained at a concentration of 0.04 M (Table 2, entries 5-10). Further optimization of the reaction with regard to the ratio of the buffer solution to CH 3 CN revealed that the yields increased as the percen-tage of the buffer solution to CH 3 CN increased; when the ratio reached 1 : 1, the yield reached a maximum of 92% (Table 2, entries [11][12][13]. The solubility of the reactants decreased and they precipitated when the amount of the buffer solution was further increased to more than 1 : 1.…”

Direct Conversion of 3-(2-Nitroethyl)-1H-Indoles into 2-(1H-Indol-2-yl)Acetonitriles

“…Herein, we disclose a new method for an efficient activation of 4 toward spirocyclization, which allowed for a straightforward access to nitriles 6. It should be noted that multiple methods for direct reductive conversion of nitroalkanes into nitriles have been reported [21][22][23][24][25][26][27][28][29]; however, the transformation described in this work is not mechanistically related to any of the known processes.…”

Methods of Nitriles Synthesis from Amines through Oxidative Dehydrogenation

“…To date, various methods for the synthesis of nitriles have been developed using different starting substrates, reagents and reaction conditions (Scheme ). Nitriles have been prepared from amines ( I ), amides ( II ), aldehydes ( III ), oximes ( IV ), amidoximes ( V ), thioamides ( VI ), alkyl‐halides/azides ( VII ), nitroalkanes ( VIII ), anilines/arylhalides ( IX ), and alcohols ( X ) . On larger scale, nitriles are commonly produced via the ammoxidation or hydrocyanation methods .…”