Electroselective and Controlled Reduction of Cyclic Imides to Hydroxylactams and Lactams

Abstract

An efficient and practical electrochemical method for selective reduction of cyclic imides has been developed using a simple undivided cell with carbon electrodes at room temperature. The reaction provides a useful strategy for the rapid synthesis of hydroxylactams and lactams in a controllable manner, which is tuned by electric current and reaction time, and exhibits broad substrate scope and high functional group tolerance even to reduction-sensitive moieties. Initial mechanistic studies suggest that the approach heavily relies on the utilization of amines (e.g., i-Pr2NH), which are able to generate α-aminoalkyl radicals. This protocol provides an efficient route for the cleavage of C–O bonds under mild conditions with high chemoselectivity.

Chemoselective Electrosynthesis Using Rapid Alternating Polarity

“…The procedure is adapted from Y. Bai et al 18 To an ElectraSyn reaction vial charged with substrate (0.1 mmol, 1.0 mmol), diisopropylamine (61 mg, 6.0 mmol), and tetrabutylammonium tetrafluoroborate (82 mg, 0.25 mmol) was added 2.5 mL of EtOH. Using a graphite anode and an RVC cathode, the reaction mixture was electrolyzed under a constant direct current of 25 mA or 30 mA for 6-12 F/mol.…”

“…While several intriguing applications of square waveform has been reported 15,16 , rAP was developed based on the following hypothesis: if the rate of polarity switching is faster than the rate of certain redox reactions on an electrode, a slower subset of electrochemical processes might be suppressed (Figure 1C). 17,18 In other words, rAP would enable differentiation of redox reactions based on their relative reaction rate so as to enable chemoselective electrosynthesis. Such a method could bring a new dimension to reaction control where differentiation of multiple redox reactions and redox-active functionality are inherently challenging based only on redox potentials.…”

Synthesis of Lactams by Reductive Amination of Carbonyl Derivatives with ω‐Amino Fatty Acids under Hydrosilylation Conditions

“…[4] Lactams can be obtained from the corresponding cyclic imides by selective reduction with red-Al (sodium bis(2methoxyethoxy)aluminium hydride) or NaCNBH 3 , [5] hydrogenation using ruthenium based catalysts, [6] TBAF or potassium hydroxide catalysed hydrosilylation [7] or electrochemical reduction. [8] Alternatively, N-substituted lactams produced from keto-acids (e. g. levulinic acid) and primary amines under reductive conditions were reported in both catalytic and catalyst-free conditions such as hydrogenation, [9] hydrogen transfer using formic acid [10] or hydrosilylation. [11] Similarly, Al(OTf) 3 -catalysed hydrosilylation of keto-amides led to the corresponding pyrrolidinones and piperidinones.…”

Current electrochemical approaches to selective deuteration

“…However, a closely related method recently developed by Xiang and co-workers enabled the selective electrochemical carbonyl reduction of imides, with ethan(ol-d) as the deuterium source (Scheme 7). 31 Using carbon electrodes in a simple undivided cell, careful control of current density and reaction time allowed differentiation between the mono-deuterated alcohol, and the bis-deuterated methylene compound. Importantly, the reduction proceeded best in the presence of diisopropylamine (6 equivalents), capable of forming an a-amino radical at the anode which facilitated deuterium atom transfer.…”