Enzyme catalysts are an integral part of green chemistry strategies towards a more sustainable and resource-efficient chemical synthesis. However, the use of biocatalysed reactions in retrosynthetic planning clashes with the difficulties in predicting the enzymatic activity on unreported substrates and enzyme-specific stereo- and regioselectivity. As of now, only rule-based systems support retrosynthetic planning using biocatalysis, while initial data-driven approaches are limited to forward predictions. Here, we extend the data-driven forward reaction as well as retrosynthetic pathway prediction models based on the Molecular Transformer architecture to biocatalysis. The enzymatic knowledge is learned from an extensive data set of publicly available biochemical reactions with the aid of a new class token scheme based on the enzyme commission classification number, which captures catalysis patterns among different enzymes belonging to the same hierarchy. The forward reaction prediction model (top-1 accuracy of 49.6%), the retrosynthetic pathway (top-1 single-step round-trip accuracy of 39.6%) and the curated data set are made publicly available to facilitate the adoption of enzymatic catalysis in the design of greener chemistry processes.

Molecular scaffolds with multiple rotationally restricted bonds allow a precise spatial positioning of functional groups. However, their synthesis requires methods addressing the configuration of each stereogenic axis. We report here a catalyst-stereocontrolled synthesis of atropisomeric multiaxis systems enabling divergence from the prevailing stereochemical reaction path. By using ion-pairing catalysts in arene-forming aldol condensations, a strong substrate-induced stereopreference can be overcome to provide structurally well-defined helical oligo-1,2-naphthylenes. The configuration of up to four stereogenic axes was individually catalyst-controlled, affording quinquenaphthalenes with a unique topology.

Owing to their favorable molecular topology, atropisomers represent particularly valuable chiral scaffolds for numerous applications throughout academic research and industry. Nevertheless, whereas various well-established catalyst-controlled methodologies allow addressing stereocenter configuration, efficient procedures to prepare axially chiral compounds in high isomeric purity are still scarce. Complementary to the comprehensive reviews in the area, this perspective article features representative advances for the catalyst-stereocontrolled synthesis of atropisomeric scaffolds. With a focus on axially chiral motifs frequently utilized in catalysis or medicinal chemistry, selected recent examples encompassing unique stereoselective transition metal, hydrogen bond, ion pairing, chiral phosphoric acid, and amine catalysis are highlighted.

At opologically well-defined atropisomeric teraryl monophosphine ligand system, prepared by ah ighly stereoselective arene-forming aldol condensation combined with ad irect ester-to-anthracene transformation, is described herein. The ligands were evaluated for gold(I)catalyzed [2+ +2] cycloadditiona nd cycloisomerization reactions as well as au nique intramolecular Pd-catalyzedC ÀN cross-coupling for the atroposelective synthesis of a Naryl-indolineb earing aC ÀNs tereogenic axis. The ligand structure induced up to 95:5 stereoselectivity in the asymmetric allylic alkylation reaction and features an interesting dynamic behavior as observed by X-ray crystallographic studies.

Atropisomeric1 ,2-naphthylene scaffolds provide access to donor-acceptor compounds with helical oligomerbased bridges,a nd transient absorption studies revealed a highly unusuald ependenceo ft he electron-transfer rate on oligomer length, whichi sd ue to their well-defined secondary structure. Close noncovalent intramolecular contacts enable shortcuts for electron transfer that would otherwise have to occur over longerd istances along covalentp athways, reminiscent of the behavior seen for certain proteins. The simplistic pictureo ft ube-like electron transferc an de-scribe this superpositiono fd ifferent pathways including both the covalenth elical backbone, as well as noncovalent contacts, contrasting the wire-like behavior reportedm any times before for more conventional molecular bridges. The exquisite control over the molecular architecture, achievable with the configurationally stable and topologically defined 1,2-naphthylene-baseds caffolds, is of key importancef or the tube-like electron transfer behavior.O ur insights are relevant for the emerging field of multidimensional electron transfer and for possible future applications in molecular electronics.Scheme1.(a) Electron transfer (ET) through linear wires;( b) ET across the covalent backboneofah elical structure;(c) conformational flexibility complicates the assessment of the relative importanceo fc ovalent versus noncovalentlypathways;and (d) ET pathway involving noncovalent contacts in ahelical structure.Scheme2.(a) Donor-acceptor dyads synthesized and investigated in this work;and (b) space-filling modelo ft he dyad with n = 3( compound W3).