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. 2024 Dec 20;29(24):6016.
doi: 10.3390/molecules29246016.

Nickel-Catalyzed Reductive Cyanation of Aryl Halides and Epoxides with Cyanogen Bromide

Yu-Juan Wu  1 , Chen Ma  1 , Muhammad Bilal  1 , Yu-Feng Liang  1
Affiliations

Nickel-Catalyzed Reductive Cyanation of Aryl Halides and Epoxides with Cyanogen Bromide

Yu-Juan Wu et al. Molecules. .

Abstract

Nitriles are valuable compounds because they have widespread applications in organic chemistry. This report details the nickel-catalyzed reductive cyanation of aryl halides and epoxides with cyanogen bromide for the synthesis of nitriles. This robust protocol underscores the practicality of using a commercially available and cost-effective cyanation reagent. A variety of aryl halides and epoxides featuring diverse functional groups, such as -TMS, -Bpin, -OH, -NH2, -CN, and -CHO, were successfully converted into nitriles in moderate-to-good yields. Moreover, the syntheses at gram-scale and application in late-stage cyanation of natural products and drugs reinforces its potentiality.

Keywords: cyanation; cyanogen bromide; nickel catalysis; nitriles; reductive coupling.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Scheme 1
Scheme 1
Preparation of nitriles via cyanation.
Scheme 2
Scheme 2
Substrate scope for aromatic nitriles. Reaction conditions: 1 (0.2 mmol), BrCN (0.4 mmol), NiCl2·1,10-phen (10 mol%), Zn (3.0 equiv), and dioxane (0.5 mL) at 50 °C for 12 h. Isolated yields.
Scheme 3
Scheme 3
Mechanistic studies for cyanation of aryl halides.
Scheme 4
Scheme 4
Substrate scope of epoxides. Reaction conditions: 3 (0.2 mmol), BrCN (0.6 mmol), NiBr2 (10 mol%), L1 (12 mol%), Mn (3.0 equiv), DBU (1.5 equiv), and dioxane (0.5 mL) at 50 °C for 12 h. Isolated yields.
Scheme 5
Scheme 5
Reaction intermediate experiments.
Figure 1
Figure 1
Reaction kinetics. (a) Reaction profile of cyanation of aryl halide 1h; (b) reaction profile of cyanation of epoxide 3a; (c) order in [NiBr2] of cyanation of epoxide 3a; (d) order in [3a] of cyanation of epoxide.
Scheme 6
Scheme 6
Proposed reaction mechanism.
See this image and copyright information in PMC

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