Catalytic enantioselective reductive domino alkyl arylation of acrylates via nickel/photoredox catalysis

Nonsteroidal anti-inflammatory drug derivatives (NSAIDs) are an important class of medications. Here we show a visible-light-promoted photoredox/nickel catalyzed approach to construct enantioenriched NSAIDs via a three-component alkyl arylation of acrylates. This reductive cross-electrophile coupling avoids preformed organometallic reagents and replaces stoichiometric metal reductants by an organic reductant (Hantzsch ester). A broad range of functional groups are well-tolerated under mild conditions with high enantioselectivities (up to 93% ee) and good yields (up to 90%). A study of the reaction mechanism, as well as literature precedence, enabled a working reaction mechanism to be presented. Key steps include a reduction of the alkyl bromide to the radical, Giese addition of the alkyl radical to the acrylate and capture of the α-carbonyl radical by the enantioenriched nickel catalyst. Reductive elimination from the proposed Ni(III) intermediate generates the product and forms Ni(I).

A New Three-Component Photo-Initiating System for Visible Light Recording of Volume Holograms with Single-Pulsed Laser

Versatile substituted electron-deficient trichloromethylarenes can easily be synthesized and combined with a Safranine O/triarylalkylborate salt to form a highly efficient three-component photo-initiation system that starts free radical polymerization to finally form holographic gratings with a single-pulsed laser. The mechanism of this photo-initiation most likely relies on an electron transfer from the borate salt into the semi-occupied HOMO of the excited dye molecule Safranine O, which after fragmentation generates an initiating alkyl radical and longer-lived dye radical species. This dye radical is most probably oxidized by the newly introduced trichloromethylarene derivative as an electron acceptor. The two generated radicals from one absorbed photon initiate the photopolymerization and form index gratings in a suitable holographic recording material. This process is purely photonic and does not require further non-photonic post treatments.

Anti-Markovnikov hydro(amino)alkylation of vinylarenes via photoredox catalysis

Photoredox catalysis is a powerful means to generate odd-electron species under mild reaction conditions from a wide array of radical precursors. Herein, we present the application of this powerful catalytic manifold to address the hydroalkylation and hydroaminoalkylation of electronically diverse vinylarenes. This reaction allows for generalized alkene hydroalkylation leveraging common alkyl radical precursors, such as organotrifluoroborate salts and carboxylic acids. Furthermore, utilizing easily accessible α-silyl amine reagents or tertiary amines directly, secondary and tertiary amine moieties can be installed onto monoaryl and diaryl alkenes to access valuable products, including γ,γ-diarylamines pharmacophores. Thus, under a unified system, both hydroalkylation and hydroaminoalkylation of alkenes are achieved. The substrate scope is evaluated through 57 examples, the synthetic utility of the method is demonstrated, and preliminary mechanistic insights are presented.

Antibacterial and Fungicidal Activity of Guanidinium Oligomers

Guanidinium oligomers are a poorly studied class of organic compounds and attract attention due to their antimicrobial properties. Strengthening the antimicrobial properties and simplifying and reducing the cost of the synthesis of these compounds is promising for obtaining functional guanidine-containing oligomers with alkyl radicals of different lengths in their composition. The aim of this work is to study the bactericidal and fungicidal activities of newly synthesized oligomeric guanidinium bromides with alkyl radicals of various lengths. Methods. The synthesis of tetraalkyl-substituted guanidine-containing oligomers with an aromatic and aliphatic oligoether component was carried out by the reaction of guanidine-containing oligomers with terminal guanidine fragments and alkyl bromides (Alk=-C3H7, -C7H15, -C10H21) at a molar ratio (1:4) of components. Different types of microorganisms (clinical isolates, gram-positive and gramnegative bacteria, microscopic fungi) were used as test cultures to determine the biocidal activity of the obtained compounds. The bacteria were grown on meat-peptone agar for 48 hours, micromycetes – on beer wort agar (6°B) for 14 days. The hydrocarbon-oxidizing bacteria and micromycetes were incubated at a temperature of 28±2°C, and clinical bacterial isolates – at a temperature of 37±2°C. Antimicrobial activity of oligomers was determined by the standard disco-diffusion method, and fungicidal – by the method of wells in agar. Results. Tetraalkyl-substituted guanidinium bromide oligomers with various radicals (-C3H7, -C7H15, -C10H21) were obtained and their bactericidal and fungicidal activity against various groups of microorganisms was shown. It was found that the obtained oligomers at a concentration of 1–3% in aqueous solution inhibited the growth of gram-negative and gram-positive bacteria. Antimicrobial and fungicidal properties depended on the length of the alkyl radical, and as its length increased, the diameter of growth inhibition zones of bacteria and micromycetes were increased. For 3% solutions of tetraalkyl-substituted guanidine oligomer with aromatic oligoepoxide (Alk=-C10H21), the growth inhibition zones of bacteria were 18–21 mm. The bactericidal effect of oligomer based on aromatic oligoepoxide with alkyl radicals Alk=-C7H15, -C10H21 was 20–25% higher than that for variants with aliphatic oligoepoxide. All the tetraalkyl-substituted (Alk=-C7H15, -C10H21) guanidine-containing oligomers at a concentration of 1% solution showed fungicidal activity to almost all micromycetes, the growth inhibition zones for microscopic fungi on the 7th day were 7–20 mm. The largest growth inhibition zones of micromycetes (in the range 15–20 mm) were observed for oligomers with aromatic oligoepoxide and radicals Alk=-C10H21 and -C7H15 and aliphatic oligoepoxide with radical Alk=-C10H21 (in the range 15–20 mm). Conclusions. The length of the alkyl radical and the nature of the oligoether component affected the bactericidal and fungicidal properties of newly synthesized oligomers. With an increase of the length of the alkyl radical of guanidine-containing oligomers, their bactericidal and fungicidal properties increase, tetralkyl-containing oligomers are promising for use as disinfectants for indoor treatment and as additives in polymer compositions to protect them from bio-damage.

A cross-dehydrogenative C(sp3)−H heteroarylation via photo-induced catalytic chlorine radical generation

Hydrogen atom abstraction (HAT) from C(sp3)–H bonds of naturally abundant alkanes for alkyl radical generation represents a promising yet underexplored strategy in the alkylation reaction designs since involving stoichiometric oxidants, excessive alkane loading, and limited scope are common drawbacks. Here we report a photo-induced and chemical oxidant-free cross-dehydrogenative coupling (CDC) between alkanes and heteroarenes using catalytic chloride and cobalt catalyst. Couplings of strong C(sp3)–H bond-containing substrates and complex heteroarenes, have been achieved with satisfactory yields. This dual catalytic platform features the in situ engendered chlorine radical for alkyl radical generation and exploits the cobaloxime catalyst to enable the hydrogen evolution for catalytic turnover. The practical value of this protocol was demonstrated by the gram-scale synthesis of alkylated heteroarene with merely 3 equiv. alkane loading.