R. Jiang

The stereoselective Michael addition of pyruvate to β-nitrostyrenes catalyzed by NahE, a type 1 aldolase, is reported. β-Aryl-γ-nitrobutyric acids can be isolated after oxidative decarboxylation in high yields on a preparative scale, providing access to precursors of γ-aminobutyric acid (GABA) analogues of demonstrated pharmacological activity.

Abstract

Michael addition reactions are highly useful in organic synthesis and are commonly accomplished using organocatalysts. However, the corresponding biocatalytic Michael additions are rare, typically lack synthetically useful substrate scope, and suffer from low stereoselectivity. Herein we report a biocatalytic nitro-Michael addition, catalyzed by NahE, that proceeds with low catalyst loading at room temperature in moderate to excellent enantioselectivity and high yields. A series of β-nitrostyrenes reacted with pyruvate in the presence of NahE to give, after oxidative decarboxylation, β-aryl-γ-nitrobutyric acids in up to 99 % yield without need for chromatography, providing a simple preparative-scale route to chiral GABA analogues. This reaction represents the first example of an aldolase displaying promiscuous Michaelase activity and opens the use of nitroalkenes in place of aldehydes as substrates for aldolases.

Photoexcitation promotes palladium-catalyzed C–N bond formation between internal alkenes and aliphatic amines.

Nature Communications, Published online: 10 December 2022; doi:10.1038/s41467-022-35394-z

Converting low-cost inorganic chemicals into value-added organic chemicals is a longstanding goal in chemistry. Here the authors describe a silver-catalysed chemoselective carbene N−H insertion reaction, providing access to primary amines from aqueous ammonia and diazo compounds.

Nature Communications, Published online: 19 December 2022; doi:10.1038/s41467-022-35468-y

Chiral heterocyclic compounds are privileged structures in medicinal chemistry. Here, the authors report an in silico strategy for the enzymatic synthesis of pharmaceutically significant chiral N- and O-heterocycles via Baldwin cyclization of hydroxy- and amino-substituted epoxides and oxetanes using epoxide hydrolase mutants.

Nature Chemistry, Published online: 07 November 2022; doi:10.1038/s41557-022-01074-0

Carbon-labelled α-amino acids are valuable compounds in drug development and nuclear medicine, but are difficult and time consuming to prepare. Now, an aldehyde-catalysed method has been developed for the direct C1-labelling of α-amino acids using *CO2 (* = 14, 13, 11), providing access to many proteinogenic and non-natural labelled α-amino acids.

Nature Chemistry, Published online: 05 December 2022; doi:10.1038/s41557-022-01092-y

Photoactivation of EDA complexes was previously limited to electronically biased partners to secure productive charge-transfer interactions. Now, the participation of triarylsulfonium salts—formed by selective C–H sulfenylation—in photoactive EDA complexes with catalytic triarylamine donors provides a site-selective and metal-free strategy for the generation of aryl radicals and the formal C–H functionalization of native arenes.

Nature Catalysis, Published online: 08 December 2022; doi:10.1038/s41929-022-00879-z

Iridium catalysis can be used to achieve the challenging Z-retentive asymmetric allylic substitution reaction by trapping thermodynamically less stable anti-π-allyliridium intermediates. Now the isolation and characterization of these complexes is reported, providing hitherto elusive detailed mechanistic insights into this reaction.

Nature Chemistry, Published online: 12 December 2022; doi:10.1038/s41557-022-01101-0

The strong regiochemical preferences of electrophilic aromatic substitution have played a key role in defining the diversity of accessible chemical space. Now, it has been shown that the electrophilic arylation of phenols can be achieved at the electronically disfavoured meta-position via a formal 1,2-migration of a key σ-complex intermediate.

Nature Catalysis, Published online: 28 November 2022; doi:10.1038/s41929-022-00875-3

Carbonyl catalysis is mainly limited to strongly activated primary amines. Now, a chiral bifunctional pyridoxal organocatalyst is developed that enables the activation of the inert α C(sp3)–H bond of NH2-unprotected benzylamines affording chiral β-aminoalcohols with high diastereo- and enantioselectivities.

Nature Catalysis, Published online: 15 December 2022; doi:10.1038/s41929-022-00881-5

Activation of inert chemical bonds employing classical photocatalysts usually involves an outer-sphere single electron transfer mechanism. Now, an alternative inner-sphere single electron transfer pathway for the homolytic cleavage of strong C–Cl bonds using gold catalysts is reported.

Nature Chemistry, Published online: 05 May 2022; doi:10.1038/s41557-022-00931-2

Enzymes, either purified or as whole-cell biocatalysts, can be concatenated into catalytic cascades and used to produce pharmaceutically relevant molecules. This Review discusses the advantages and requirements of multistep enzyme cascades and also highlights how they can be harnessed to achieve highly sustainable and cost-efficient syntheses.

Nature, Published online: 02 March 2022; doi:10.1038/s41586-021-04365-7

A study presents a biocatalytic method for the formation of sterically hindered biaryl bonds, providing a tunable approach for assembling molecules with catalyst-controlled reactivity, site selectivity and atroposelectivity.