Electrochemical Organic Synthesis Mediated by Sodium Bromide

Original Article:
Halogen-mediated electrochemical organic synthesis

Hai-Tao Tang, et al.

Organic & Biomolecular Chemistry 18.28 (2020): 5315-5333.

10.1039/D0OB01008A

Organic electrosynthesis has outstanding advantages such as mild reaction conditions, easy control of the reaction process, high material utilization rate, and low energy consumption. Among various mediators, the halide anion-halogen system is one of the most suitable mediator systems for selective organic synthesis and large-scale processes. Common halogen-containing electrolytes are NaX, KX, NH₄X or n-Bu₄NX. We focus on the transformation of sodium bromide (NaBr) as a mediator in electrochemical organic reactions and the catalytic cycle of reactions with substrates. Herein, NaBr-mediated electrochemical organic synthesis can be briefly introduced from several aspects, including NaBr-mediated C-C bond formation, NaBr-mediated c-heteroatom bond formation, and NaBr-mediated enantioselective synthesis.

NaBr-mediated C-C Bond Formation

• 1,1,2,2-Tetracyanocyclopropane can be obtained by electrolysis of malononitrile and ketone or aldehyde with sodium bromide dissolved in ethanol as the medium.

Synthesis of 1,1,2,2-tetracyanocyclopropanes.

• Under NaBr-mediated conditions, the electrolysis of substituted 1,1,2,2-tetracyanocyclopropanes provides substituted 2-amino-4,4-dialkoxy-1,5-dicyano-3-azabicyclo[3.1.0]hex-2 -enes in 70%-95% yields.

Synthesis of 2-amino-4,4-dialkoxy-1,5-dicyano-3-azabicyclo[3.1.0]hex-2-enes.

• Under almost the same electrochemical conditions and mechanism as the reaction of malononitrile with ketones or aldehydes, Elinson et al. reported that alkylene cyanoacetate and malonate were electrolyzed to form 3- Substituted 2-cyanocyclopropane-1,1,2-tricarboxylate.

Synthesis of 3-substituted 2-cyanocyclopropane-1,1,2-tricarboxylates.

• In 2013, Wang and colleagues reported an electrochemical route to construct spirodihydrofuran scaffolds with excellent yields. The process uses a catalytic amount of sodium bromide as a redox catalyst and is carried out in an undivided cell at a constant current density.

Synthesis of spiro dihydrofuran scaffolds.

NaBr-mediated C -Heteroatom Bond Formation

• Indirect electrochemical oxidation of 1-N-substituted piperidin-4-ones in MeOH in the presence of NaBr/NaOMe system to generate corresponding α-hydroxy ketals via NaBr/NaOH mediated system and indirect electrochemical oxidation.

Synthesis of α-hydroxyketals with 1-N-subsituted piperidin-4-ones.

• In 2018, Zeng et al. reported the in situ electrochemical generation of N-acyloxy amidyl radicals through the inner-sphere electron-transfer process for the first time.

Synthesis of lactam via intramolecular amination.

• A key intermediate in the synthesis of the PRAP inhibitor PJ34 was synthesized in 87% yield on a gram-scale basis by an established electrochemical method.

Synthesis of PJ34 and Phenaglaydon.

NaBr-Mediated Enantioselective Synthesis

To date, few enantioselective syntheses via electrochemical reactions have been disclosed. Tanaka and co-workers performed electrooxidative kinetic resolution of sodium bromide and optically active N-oxyl-mediated secondary alcohols in a CH₂Cl₂-H₂O two-phase system by using an undivided cell under constant flow conditions. This work is the first example of enantioselective electrooxidation, which provides facile operation for high current efficiency and satisfactory selectivity.

Kinetic resolution of sec-alcohols.

Chemicals Related in the Paper:

Catalog Number	Product Name	CAS Number
ACM7647156	Sodium bromide	7647-15-6
ACM7647157	Sodium bromide industrial grade 98.5+%	7647-15-7