Asymmetric photoredox transition-metal catalysis activated by visible light.

Asymmetric catalysis is seen as one of the most economical strategies to satisfy the growing demand for enantiomerically pure small molecules in the fine chemical and pharmaceutical industries. And visible light has been recognized as an environmentally friendly and sustainable form of energy for triggering chemical transformations and catalytic chemical processes. For these reasons, visible-light-driven catalytic asymmetric chemistry is a subject of enormous current interest. Photoredox catalysis provides the opportunity to generate highly reactive radical ion intermediates with often unusual or unconventional reactivities under surprisingly mild reaction conditions. In such systems, photoactivated sensitizers initiate a single electron transfer from (or to) a closed-shell organic molecule to produce radical cations or radical anions whose reactivities are then exploited for interesting or unusual chemical transformations. However, the high reactivity of photoexcited substrates, intermediate radical ions or radicals, and the low activation barriers for follow-up reactions provide significant hurdles for the development of efficient catalytic photochemical processes that work under stereochemical control and provide chiral molecules in an asymmetric fashion. Here we report a highly efficient asymmetric catalyst that uses visible light for the necessary molecular activation, thereby combining asymmetric catalysis and photocatalysis. We show that a chiral iridium complex can serve as a sensitizer for photoredox catalysis and at the same time provide very effective asymmetric induction for the enantioselective alkylation of 2-acyl imidazoles. This new asymmetric photoredox catalyst, in which the metal centre simultaneously serves as the exclusive source of chirality, the catalytically active Lewis acid centre, and the photoredox centre, offers new opportunities for the 'green' synthesis of non-racemic chiral molecules.

Synthesis of Fluorescent 1-(3-Amino-4-(4-(tert-butyl)phenyl)-6-(p-tolyl)furo[2,3-b]pyridin-2-yl)ethan-1-one: Crystal Structure, Fluorescence Behavior, Antimicrobial and Antioxidant Studies.

Furopyridine III, namely 1-(3-amino-4-(4-(tert-butyl)phenyl)-6-(p-tolyl)furo[2,3-b]pyridin-2-yl)ethan-1-one, synthesized from 4-(4-(tert-butyl)phenyl)-2-oxo-6-(p-tolyl)-1,2-dihydropyridine-3-carbonitrile I in two steps. The title compound is characterized by NMR, MS and its X-ray structure. The molecular structure consists of planar furopyridine ring with both phenyl rings being inclined from the furopyridine scaffold to a significant different extent. There are three intramolecular hydrogen bonds within the structure. The lattice is stabilized by N-H…O, H2C-H …π and π…π intermolecular interactions leading to three-dimensional network. Compound III exhibits fluorescent properties, which are investigated. Antimicrobial potential and antioxidant activity screening studies for the title compound III and the heterocyclic derivatives, I and II, show no activity towards neither bacterial nor fungal strains, while they exhibited weak to moderate antioxidant activity compared to reference.

Synthesis of ß-Substituted γ-Aminobutyric Acid Derivatives through Enantioselective Photoredox Catalysis.

ß-Substituted chiral γ-aminobutyric acids feature important biological activities and are valuable intermediates for the synthesis of pharmaceuticals. Herein, an efficient catalytic enantioselective approach for the synthesis of ß-substituted γ-aminobutyric acid derivatives through visible-light-induced photocatalyst-free asymmetric radical conjugate additions is reported. Various ß-substituted γ-aminobutyric acid analogues, including previously inaccessible derivatives containing fluorinated quaternary stereocenters, were obtained in good yields (42-89 %) and with excellent enantioselectivity (90-97 % ee). Synthetically valuable applications were demonstrated by providing straightforward synthetic access to the pharmaceuticals or related bioactive compounds (S)-pregabalin, (R)-baclofen, (R)-rolipram, and (S)-nebracetam.

Octahedral Ruthenium Complex with Exclusive Metal-Centered Chirality for Highly Effective Asymmetric Catalysis.

A novel ruthenium catalyst is introduced which contains solely achiral ligands and acquires its chirality entirely from octahedral centrochirality. The configurationally stable catalyst is demonstrated to catalyze the alkynylation of trifluoromethyl ketones with very high enantioselectivity (up to >99% ee) at low catalyst loadings (down to 0.2 mol%).

A Rhodium Catalyst Superior to Iridium Congeners for Enantioselective Radical Amination Activated by Visible Light.

A bis-cyclometalated rhodium(III) complex catalyzes a visible-light-activated enantioselective α-amination of 2-acyl imidazoles with up to 99 % yield and 98 % ee. The rhodium catalyst is ascribed a dual function as a chiral Lewis acid and, simultaneously, as a light-activated smart initiator of a radical-chain process through intermediate aminyl radicals. Notably, related iridium-based photoredox catalysts reported before were unsuccessful in this enantioselective radical C-N bond formation. The surprising preference for rhodium over iridium is attributed to much faster ligand-exchange kinetics of the rhodium complexes involved in the catalytic cycle, which is crucial to keep pace with the highly reactive and thus short-lived nitrogen-centered radical intermediate.

Improved δ-valerolactam templates for the assembly of Aß-miniamyloids by boronic ester formation.

The 6,7,8,8a-cis (all-cis) substituted δ-valerolactams of type 10, 11 and 12 are high-affinity diols for boronic ester formation, superior to the corresponding 6,7-trans analogues 1, 3 and 4. X-ray and NMR structure analysis have identified the differences of the six-membered ring conformations which cause the improved esterification properties of the all-cis stereoisomers. The homooligomeric all-cisδ-valerolactams 46-48 are used as polyol templates for the self-assembly of peptidic oligomers 49-52 by dynamic covalent chemistry. The templates have a diol spacing of approximately 5 Å, suitable for the assembly of branched peptides from the quantitative reaction between the peptide of interest, 2-formylphenylboronic acid and the respective template. According to this strategy, the tetrameric Aß-miniamyloid 52 formed spontaneously from nine individual molecules in a three-component system. A detailed NMR analysis based on the complete sequential assignment of the trimeric Aß(32-40)-miniamyloid 51 identified its three-dimensional structure in solution.

Regioselective Ring-Opening Polymerization of a Polyhydroxycarboxylic Acid for the Synthesis of a Nanoscale Carrier Material with pH-Dependent Stability and Sustained Drug Release.

Synthetic polyesters are usually composed of monohydroxycarboxylic acids to avoid the problem of regioselectivity during ring-opening polymerization. In contrast, the linear polyester BICpoly contains four secondary OH groups and is nevertheless esterified regioselectively at only one of these positions. Neither the synthesis of the tricyclic monomers nor the ring-opening polymerization requires protecting groups, making BICpoly an attractive novel and biocompatible polymer. BICpoly nanoparticles can be loaded with low-molecular weight drugs or coated onto surfaces as thin films. The release of loaded compounds makes BICpoly an attractive depot for drug release, as shown herein by loading BICpoly with dyes or the cytostatic drug doxorubicin. BICpoly is distinguishable from other polymers by its characteristic pH-dependent degradation.

Unexpected formation of a co-crystal containing the chalcone (E)-1-(5-chloro-thio-phen-2-yl)-3-(3-methyl-thio-phen-2-yl)prop-2-en-1-one and the keto-enol tautomer (Z)-1-(5-chloro-thio-phen-2-yl)-3-(3-methyl-thio-phen-2-yl)prop-1-en-1-ol.

The title crystal structure is assembled from the superposition of two mol-ecular structures, (E)-1-(5-chloro-thio-phen-2-yl)-3-(3-methyl-thio-phen-2-yl)prop-2-en-1-one, C12H9ClOS2 (93%), and (Z)-1-(5-chloro-thio-phen-2-yl)-3-(3-methyl-thio-phen-2-yl)prop-1-en-1-ol, C12H11ClOS2 (7%), 0.93C12H9ClOS2·0.07C12H11ClOS2. Both were obtained from the reaction of 3-methyl-thio-phene-2-carbaldehyde and 1-(5-chloro-thio-phen-2-yl)ethanone. In the extended structure of the major chalcone component, mol-ecules are linked by a combination of C-H⋯O/S, Cl⋯Cl, Cl⋯π and π-π inter-actions, leading to a compact three-dimensional supra-molecular assembly.

(S,2S,3R)-2-(2-Methyl-propane-2-sulfin-amido)-3-phenyl-butyronitrile.

The absolute configuration has been determined for the title compound, C(14)H(20)N(2)OS. Inter-molecular N-H⋯O hydrogen bonds are observed in the crystal packing, forming infinitive one-dimensional chains with the base vector [100].

(S,2S,3S)-2-(2-Methyl-propan-2-sulfin-amido)-3-phenyl-butyronitrile.

The absolute configuration has been determined for the title compound, C(14)H(20)N(2)OS. There are two independent mol-ecules in the asymmetric unit. Inter-molecular N-H⋯O hydrogen bonds are observed in the crystal packing, forming infinite chains with the base vectors [100] and [010]. Each chain contains only one of the two independent mol-ecules.

Synthesis, characterization, crystal structure and supra-molecularity of ethyl (E)-2-cyano-3-(3-methyl-thio-phen-2-yl)acrylate and a new polymorph of ethyl (E)-2-cyano-3-(thio-phen-2-yl)acrylate.

The synthesis, crystal structure and structural motif of two thio-phene-based cyano-acrylate derivatives, namely, ethyl (E)-2-cyano-3-(3-methyl-thio-phen-2-yl)acrylate (1), C11H11NO2S, and ethyl (E)-2-cyano-3-(thio-phen-2-yl)acrylate (2), C10H9NO2S, are reported. Derivative 1 crystallized with two independent molecules in the asymmetric unit, and derivative 2 represents a new monoclinic (C2/m) polymorph. The mol-ecular conformations of 1 and the two polymorphs of 2 are very similar, as all non-H atoms are planar except for the methyl of the ethyl groups. The inter-molecular inter-actions and crystal packing of 1 and 2 are described and compared with that of the reported monoclinic (C2/m) polymorph of derivative 2 [Castro Agudelo et al. (2017 ▸). Acta Cryst. E73, 1287-1289].

[Lithium tert-butylperoxide]12 : Crystal Structure of an Aggregated Oxenoid.

The X-ray crystal structure of the dodecameric lithium tert-butylperoxide [2]12 is the first of an alkali or alkaline earth peroxide. It shows the lithium ion bridging the two oxygen atoms of the peroxide unit and a slight lenghtening of the O-O bond, in agreement with quantum-chemical calculations. A calculation for the model reaction of MeLi with LiOOH to give MeOLi and LiOH reveals the importance of Li bridging the O-O bond in the transition state of this reaction, as similarly discussed for many oxidation reactions of (transition-) metal peroxides. Preliminary theoretical studies of the O-O bond length (and thus of the oxenoid character) as a function of the aggregation of 2 disclose that increasing aggregation leads to stabilization of the charge at the anionic oxygen atom and thus to a reduction of the O-O bond length (oxenoid character). Related considerations of the effect of aggregation should also be valid for other lithium (organometallic) compounds and their structure and reactivity as well as other properties.

The Crystal Structures of a Lower Order and a "Higher Order" Cyanocuprate: [tBuCu(CN)Li(OEt2 )2 ]∞ and [tBuCutBu{Li(thf)(pmdeta)}2 CN].

Different types of bonding are present in cyanocuprates 1 and 2, whose crystal structures could be determined (the drawings below show the important structural characteristics). Accordingly, 1 is a lower order cyanocuprate of the type RCu(CN)Li, whereas 2, which is of the type R2 Cu(CN)Li2 , does not exist as a "higher order" cyanocuprate with Cu-CN bonds, but rather as a cyano-Gilman cuprate.

[(Ph)2 (NMe2 )C(OLi)⋠THF]2 : Crystal Structure of the Tetrahedral Intermediate Formed in the Reaction of N,N-Dimethylbenzamide and Phenyllithium.

Information on the reaction path for the 1,2-eliminiation of LiNMe2 to form benzophenone is provided by the X-ray crystal structure analysis of the tetrahedral adduct [(Ph)2 (NMe2 )C(OLi)⋅THF]2 (a portion of the structure is shown schematically), which is prepared from N,N-dimethylbenzamide and phenyllithium. A N1-Li1 interaction, which is not observed, would lead to loss of the anomeric effect (nN →σ*C-O ) as well as high conformational strain along the C1-N1 bond.