The electrochemical deoxygenation of alcohol for functionalization of heteroarenes has been recently reported in Angew. Chem. Int. Ed （DOI: 10.1002/anie.202001571）by Wang and Pan group at School of Chemistry & Chemical Engineering, Nanjing University.
Alcohols are among the most available feedstock in food and chemical industry. The delivery of alkyl radicals through dehydroxylation of alcohols under mild conditions is strategically appealing. However, due to the strong C-O bonding energy (BDE∼95 kcal/mol) and high redox potentials of unactivated alcohols, radical cleavage of hydroxyl functionality requires harsh conditions and represent tremendous difficulties. Inevitable high temperatures and toxic tin reagents limited the application, primary and secondary alcohols are generally inapplicable to such process. In 2019, the group of Wang and Pan has achieved a series of electrochemical functionalization of heteroarenes including thiolation (ACS Catal. 2019, 9, 1630−1634) and aryl migration（Org.Lett. 2019, 21, 1857-1862）. It is meaningful to design a mild electrochemical deoxygenative process from alcohol for the preparation of heteroaryl derivatives.
Figure 1 Origin of the design
The authors realized that simple alkyl carbazates could undergo dehydrazinative acylation and release molecular nitrogen under iron-catalyzed oxidative conditions. They envisioned that under suitable cell conditions, further anodic oxidative decarboxylation could occur to furnish alkyl radical. They have employed carbazate as a new electrochemically activated alkylating agent for direct functionalization of heteroarenes with an oxidative dehydrazination/decarboxylation sequence (Figure 1).
The simple undivided cell at low oxidative potentials with carbon/platinum electrode set-ups offers excellent substrate tolerance, affording a variety of primary, secondary and tertiary alkyl-decorated heterocycles in good chemical yields.Notably, bioactive natural products are also compatible with this reaction (Figure 2).
Figure 2 Alcohol scope
A variety of heterocycles including benzoquinoxalinone , pyrazinone, quinazolinone, isoquinoline, phthalazine, quinazoline, and phenanthridine were susceptible to the reaction conditions to acheive the corresponding alkylated products (Figure 3).
Figure 3 Heteroarene scope
Control reactions have been carried out to elucidate a stepwise dehydrazination-decarboxylation sequence was involved in the electrochemical fragmentation of carbazate. Furthermore, the cyclic voltammetry results demonstrated that carbazate can be easily oxidized under electrochemical conditions. Based on the experimental facts, a plausible reaction mechanism is proposed. The first stage is consecutive anodic oxidation of carbazate and deprotonation to generate hydrazinecarboxylate radical B and diazenecarboxylate C. Further anodic oxidation cleaves diazene to form acyl radical E and releases molecular nitrogen. The second step is decarboxylation of acyl radical E to furnish alkyl radical F (Figure 4).
Figure 4 Mechanistic Study
The work is accomplished by PhD student Yongyuan Gao at our school and supported by NSFC (21772085 , 21971107), State Key Laboratory of Coordination Chemistry and Provincial Key Laboratory of Advanced Organic Materials.