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A mild photocatalytic phenol oxygenation enabled by a continuous-flow photoreactor using visible light and pressurized air is described herein. Products for wide-ranging applications, including the synthesis of vitamins, were obtained in high yields by precisely controlling principal process parameters. The reactor design permits low organophotocatalyst loadings to generate singlet oxygen. It is anticipated that the efficient aerobic phenol oxygenation to benzoquinones and p-quinols contributes to sustainable synthesis., (© 2021 Wiley-VCH GmbH.)

A topologically well-defined atropisomeric teraryl monophosphine ligand system, prepared by a highly stereoselective arene-forming aldol condensation combined with a direct ester-to-anthracene transformation, is described herein. The ligands were evaluated for gold(I)-catalyzed [2+2] cycloaddition and cycloisomerization reactions as well as a unique intramolecular Pd-catalyzed C-N cross-coupling for the atroposelective synthesis of a N-aryl-indoline bearing a C-N stereogenic 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., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Atropisomeric 1,2-naphthylene scaffolds provide access to donor-acceptor compounds with helical oligomer-based bridges, and transient absorption studies revealed a highly unusual dependence of the electron-transfer rate on oligomer length, which is due to their well-defined secondary structure. Close noncovalent intramolecular contacts enable shortcuts for electron transfer that would otherwise have to occur over longer distances along covalent pathways, reminiscent of the behavior seen for certain proteins. The simplistic picture of tube-like electron transfer can describe this superposition of different pathways including both the covalent helical backbone, as well as noncovalent contacts, contrasting the wire-like behavior reported many 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-based scaffolds, is of key importance for the tube-like electron transfer behavior. Our insights are relevant for the emerging field of multidimensional electron transfer and for possible future applications in molecular electronics., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The fundamental role that aldol chemistry adopts in various disciplines, such as stereoselective catalysis or the biosynthesis of aromatic polyketides, illustrates its exceptional versatility. On the one hand, numerous aldol addition reactions reliably transfer the stereochemical information from catalysts into various valuable products. On the other hand, countless aromatic polyketide natural products are produced by an ingenious biosynthetic machinery based on arene-forming aldol condensations. With the aim of complementing aldol methodology that controls stereocenter configuration, we recently combined these two tenets by investigating small-molecule-catalyzed aldol condensation reactions that stereoselectively form diverse axially chiral compounds through the construction of a new aromatic ring., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The preference of β-fluoroimines to adopt a gauche conformation has been studied by single-crystal X-ray diffraction analysis and DFT methods. Empirical and theoretical evidence for a preferential gauche arrangement around the NCCF torsion angle (φ) is presented ((E)-2-fluoro-N-(4-nitrobenzylidene)ethanamine: φ(NCCF) =70.0°). In the context of this study, the analysis of a pyridoxal-derived β-fluoroaldimine was performed, a species that is implicated in the inhibition of pyridoxal phosphate (PLP)-dependent enzymes by β-fluoroamine derivatives. The gauche preference of the internal aldimine (=NCH(2)CH(2)F) that can be rationalized by stereoelectronic arguments does not hold for the corresponding external system (N=CHCH(2)F) (E(min) when φ(NCCF) =120°). Moreover, the C-F bond is lengthened by more than 0.02 Å at φ(NCCF) =±90°, when it is exactly antiperiplanar to the conjugated imine. This activation of the C-F σ bond by an adjacent π system constitutes an addendum to Dunathan's stereoelectronic hypothesis., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Herein we report the synthesis of a series of C9-fluorinated quinine alkaloids by direct nucleophilic deoxyfluorination. This transformation gives rise to products bearing both S- and R-configured monofluoromethylene functionalities, consistent with an S(N)1-like mechanism. Furthermore, a series of ring-expanded 1-azabicyclo[3.2.2]nonane systems were generated by a skeletal rearrangement of the quinuclidine core. The modified alkaloids were converted to the corresponding hydrochloride salts and characterised by single-crystal X-ray diffraction analysis. The preference of the benzylic fluorine atom to adopt a gauche conformation relative to the protonated quinuclidine nitrogen atom was consistently observed throughout the cage-conserved compounds. Conversely, the molecular architecture of the 1-azabicyclo[3.2.2]nonane systems enforced an anti relationship between the fluorine atom and the protonated tertiary amine. This constitutes the first X-ray evidence of a vicinal fluorine atom at a stereogenic centre positioned anti to a substituted ammonium cation. The pharmacological efficacy of these compounds was assessed in vitro against the NF54 strain of Plasmodium falciparum (sensitive to all known antimalarial drugs). IC(50) values of as low as 267 nM were observed; this highlights the potential of these materials in developing novel agents for parasite chemotherapy.