Mechanochemical Oxidative Mannich Reaction: Evaluation of Chemical and Mechanical Parameters for the Mild and Chemoselective Coupling of N‐tert‐butoxycarbonyltetrahydroquinolines and Ketones

Abstract

A mechanochemical oxidative Mannich reaction of N‐tert‐butoxycarbonyl (Boc) tetrahydroquinolines and ketones was successfully developed under solvent‐free ball‐milling conditions. The reaction afforded the desired coupling products in satisfactory yields under mild and tractable oxidative conditions. Side reactions such as deprotection of the Boc group were prevented by carefully adjusting the milling parameters, including milling frequency, time, milling‐ball filling degree, milling‐ball size, and grinding auxiliary. Further examination of the scope indicated that the reaction system could also be applied to the N‐benzyloxycarbonyl and N‐aryl substrates to afford the corresponding products in moderate to good yields.

Encaging palladium(0) in layered double hydroxide: A sustainable catalyst for solvent-free and ligand-free Heck reaction in a ball mill

“…Furthermore, the sharp decrease in the yield could be also observed in 5 mm, 8 mm and 10 mm milling-ball systems with a filling degree over 0.25, which might be due to the overfull ball-milling jar and the overabundant energy input. These results mentioned above are consistent with the previous studies reported by us [ 53 ] and the others [ 52 , 54 ].…”

Investigations of the Copper‐Catalyzed Oxidative Cross‐Coupling of Tetrahydroisoquinolines with Diethylzinc by a Combination of Mass Spectrometric and Electrochemical Methods

“…In EC/MS experiments, electrochemically formed iminium species 4 d reacts directly with the electrospray solvent (Figure S10, Supporting Information). This also explains why reported CDC reactions of 1 d have involved neat reaction conditions . Among the tested THIQ derivatives bearing alternative protective groups, the photolabile N ‐(2‐acetoxyethyl)‐THIQ 1 c proved to be the most promising as a suitable surrogate with the CuCl 2 /O 2 system, even though initial studies following our original reaction protocol did not result in any conversion.…”

A solvent-free mechanochemical synthesis of polyaromatic hydrocarbon derivatives

“…35,36 In order to gain a better understanding of this phenomenon, we added milling aids such as silica gel, which has been shown to provide signicant rate enhancements of mechanochemical processes. [37][38][39][40] Upon adding silica gel to the reaction mixture, we observed a signicant rate enhancement on the reactivity of the anthracene substrates. Currently, we are investigating the inuence of silica gel on these reactions in order to get a better understanding of this effect.…”