A Rearrangement in the Nenitzescu Reaction of Cycloheptene with Acetyl Chloride and Aluminum Chloride

Process Research and Impurity Control Strategy of Esketamine

“…The Nenitzescu reductive acylation is one of the important methods to prepare ketones with mild reaction conditions, and the raw materials used are cheaper than bromocyclopentane. Therefore, the cheaper o -chlorobenzoyl chloride and cyclopentene were used to replace the Grignard reagent as raw materials to prepare 4 via the Nenitzescu reductive acylation reaction. , …”

“…In the general procedure for the reductive acylation reaction, 2 mol of aluminum chloride (AlCl 3 ) was added to a mixture of the olefin and acyl chloride in the cyclohexane solvent at about −l0 °C, and upon warming slowly to 70 °C, HCl was evolved and the saturated ketone was obtained. , The probable mechanism for the preparation of 4 is shown in Scheme . The reaction process was divided into two stages, and the intermediates 14 , 15 , and 17 were obtained via Friedel–Crafts acylation in the first stage.…”

A Copper(II) Triflate‐Catalyzed Tandem Friedel–Crafts Alkylation/Cyclization Process towards Dihydroindenes

“…Although we were unable to isolate intermediate 3 , it was clearly observed from the final product that this methyl migration process was very efficient in this system. In the final step, intermediate 3 underwent an acid‐induced intramolecular alkylation to form cyclized product 7 8,17. The preference to form the stable final product 7 may be the major factor in determining the equilibria of the previous two steps, in which the forward reaction was favored, forming the desired intermediates.…”

“…In the final step, intermediate 3 underwent an acid-induced intramolecular alkylation to form cyclized product 7. [8,17] The preference to form the stable final product 7 may be the major factor in determining the equilibria of the previous two steps, in which the forward reaction was favored, forming the desired intermediates. In summary, CuA C H T U N G T R E N N U N G (OTf) 2 catalyzed the first allylation step of the reaction and the hydrogen chloride that was generated from the first step played important roles in the methyl migration and the intramolecular alkylation steps, vide infra.…”

“…In the final step, intermediate 3 underwent an acid-induced intramolecular alkylation to form cyclized product 7. [8,17] The preference to form the stable final product 7 may be the major factor in determining the equilibria of the previous two steps, in which the forward reaction was favored, forming the desired intermediates.…”