ABSTRACT
Azetidines are prominent structural scaffolds in bioactive molecules, medicinal chemistry, and ligand design for transition metals. However, state-of-the-art methods cannot be applied to intramolecular hydroamination of allylic amine derivatives despite their underlying potential as one of the most prevalent synthetic precursors to azetidines. Herein, we report an electrocatalytic method for intramolecular hydroamination of allylic sulfonamides to access azetidines for the first time. The merger of cobalt catalysis and electricity enables the regioselective generation of key carbocationic intermediates, which could directly undergo intramolecular C-N bond formation. The mechanistic investigations including electrochemical kinetic analysis suggest that either the catalyst regeneration by nucleophilic cyclization or the second electrochemical oxidation to access the carbocationic intermediate is involved in the rate-determining step (RDS) of our electrochemical protocol and highlight the ability of electrochemistry in providing ideal means to mediate catalyst oxidation.
ABSTRACT
We have developed an electrochemically driven strategy for the stereoselective synthesis of protected syn-1,2-diols from vinylarenes with N,N-dimethylformamide (DMF). The newly developed system obviates the need for transition metal catalysts or external oxidizing agents, thus providing an operationally simple and efficient route to an array of protected syn-1,2-diols in a single step. This reaction proceeds via an electrooxidation of olefin, followed by a nucleophilic attack of DMF. Subsequent oxidation and nucleophilic capture of the generated carbocation with a trifluoroacetate ion is proposed, which gives rise predominantly to a syn-diastereoselectivity upon the second nucleophilic attack of DMF.
