Ni-Electrocatalytic C(sp3)–C(sp3) Doubly Decarboxylative Coupling

This work presents a modern spin on one of the oldest known Csp3–Csp3 bond forming reactions in synthetic chemistry: the Kolbe electrolysis. This reaction holds incredible promise for synthesis, yet its use has been near non-existent in mainstream organic synthesis. In contrast to the strongly oxidative electrolytic protocol employed traditionally since the 19th century, the present method utilizes in situ generated redox-active esters (RAEs) which are combined with a mildly reductive Ni-electrocatalytic cycle. It can be used to heterocouple 1o, 2o, and even certain 3o RAEs with a protocol reminiscent of amide bond formation in terms of simplicity. Due to its mild nature the reaction tolerates a range of functional groups, is scalable, and was strategically enlisted for the synthesis of 25 known compounds to reduce overall step-counts by 74%.

One-Step Biocatalytic Synthesis of Sustainable Surfactants Using Selective Amide Bond Formation

N-alkanoyl-N-methylglucamides (MEGAs) are non-toxic surfactants widely used in pharmaceutical and biochemical applications and hence more sustainable syntheses towards these compounds are highly desired. Here we present an aqueous, enzymatic synthesis route towards MEGAs and analogues using carboxylic acid reductase (CAR), which has been engineered to catalyse amide bond formation (CAR-A). Compared to lipase catalysed reactions, this biocatalyst is capable of selective amide bond formation between amino-polyols and fatty acids without the competing esterification reaction being observed. The wide substrate scope of CAR-A catalysed amidation was exemplified by the synthesis of 16 amides including several commercially relevant targets. The ATP co-factor could be recycled from cheap polyphosphate using a kinase. This work establishes acyl-phosphate mediated chemistry as a selective strategy for biocatalytic amide bond formation in the presence of competing alcohol functionalities.

Asymmetric biomimetic transamination of α-keto amides to peptides

Peptides are important compounds with broad applications in many areas. Asymmetric transamination of α-keto amides can provide an efficient strategy to synthesize peptides, however, the process has not been well developed yet and still remains a great challenge in both enzymatic and catalytic chemistry. For biological transamination, the high activity is attributed to manifold structural and electronic factors of transaminases. Based on the concept of multiple imitation of transaminases, here we report N-quaternized axially chiral pyridoxamines 1 for enantioselective transamination of α-keto amides, to produce various peptides in good yields with excellent enantio- and diastereoselectivities. The reaction is especially attractive for the synthesis of peptides made of unnatural amino acids since it doesn’t need great efforts to make chiral unnatural amino acids before amide bond formation.