Visible light-driven dearomative ring expansion of (aza)arenes to access dihydrofuran-based polycyclic compounds.

The dearomative expansion of aromatic rings has long been pursued by chemists due to its potential to provide tractable approaches for synthesizing valuable non-aromatic molecules. To circumvent the conventional use of hazardous and unstable diazo compounds, photochemical synthesis has recently emerged as a promising platform. However, protocols that can effectively handle both arenes and azaarenes remain scarce. Herein, we introduce a generic strategy that efficiently converts ß-(aza)aryl-ß-substituted enones into biologically significant cycloheptatriene derivatives, including their aza-variants. This method allows for the easy modulation of diverse functional groups on the product and demonstrates a wide substrate scope, evidenced by its excellent tolerance to various drug motifs and good compatibility with five-membered azaarenes undergoing ring expansion. Moreover, DFT calculations of plausible mechanisms have motivated the implementation of an important cascade diradical recombination strategy for 1,3-dienones, thus facilitating the synthesis of valuable 2-oxabicyclo[3.1.0]hex-3-ene derivatives.

Asymmetric photoredox catalytic formal de Mayo reaction enabled by sensitization-initiated electron transfer.

Visible-light-driven photoredox catalysis is known to be a powerful tool for organic synthesis. Its occurrence critically depends on the twice exothermic single-electron transfer processes of photosensitizers, which are governed by the redox properties of the species involved. Hence, the inherently narrow range of redox potentials of photosensitizers inevitably constrains their further availability. Sensitization-initiated electron transfer has recently been found to effectively overcome this substantial challenge. However, feasible and practical strategies for designing such complicated catalytic systems are rather scarce. Herein we report an elaborate dual-catalyst platform, with dicyanopyrazine as a visible light photosensitizer and a pyrenyl-incorporated chiral phosphoric acid as a co-sensitizer, and we demonstrate the applicability of this sensitization-initiated electron transfer strategy in an asymmetric formal de Mayo-type reaction. The catalysis platform enables otherwise thermodynamically unfavourable electron transfer processes to close the redox cycle and allows for precise access to valuable enantioenriched 1,5-diketones with a wide substrate range.

Radical Cross Coupling and Enantioselective Protonation through Asymmetric Photoredox Catalysis.

An unprecedented enantioselective protonation reaction enabled by photoredox catalytic radical coupling is developed. Under cooperative dicynopyrazine-derived chromophore (DPZ) as a photosensitizer and a chiral phosphoric acid catalyst, and Hantzsch ester as a sacrificial reductant, the transformations between α-substituted enones and cyanoazaarenes or 2-(chloromethyl)azaaren-1-iums can proceed a tandem reduction, radical coupling, and enantioselective protonation process efficiently. Two classes of pharmaceutically important enantioenriched azaarene variants, which contain a synthetically versatile ketone-substituted tertiary carbon stereocenter at the ß- or γ-position of the azaarenes, are synthesized with high yields and ees.

Asymmetric Olefin Isomerization via Photoredox Catalytic Hydrogen Atom Transfer and Enantioselective Protonation.

Asymmetric olefin isomerization can be appreciated as an ideal synthetic approach to access valuable enantioenriched C═C-containing molecules due to the excellent atom economy. Nonetheless, its occurrence usually requires a thermodynamic advantage, namely, a higher stability of the product to the substrate. It has thus led to rather limited examples of success. Herein, we report a photoredox catalytic hydrogen atom transfer (HAT) and enantioselective protonation strategy for the challenging asymmetric olefin isomerization. As a paradigm, by establishing a dual catalyst system involving a visible light photosensitizer DPZ and a chiral phosphoric acid, with the assistance of N-hydroxyimide to perform HAT, a wide array of allylic azaarene derivatives, featuring α-tertiary carbon stereocenters and ß-C═C bonds, was synthesized with high yields, ees, and E/Z ratios starting from the conjugated α-substituted alkenylazaarene E/Z-mixtures. The good compatibility of assembling deuterium on stereocenters by using inexpensive D2O as a deuterium source further underscores the broad applicability and promising utility of this strategy. Moreover, mechanistic studies have provided clear insights into its challenges in terms of reactivity and enantioselectivity. The exploration will robustly inspire the development of thermodynamically unfavorable asymmetric olefin isomerizations.

Catalytic Asymmetric Intermolecular [3 + 2] Photocycloaddition of Cyclopropylamines with Electron-Deficient Olefins.

An enantioselective intermolecular [3 + 2] cycloaddition of N-arylcyclopropylamines with 2-aryl acrylates/ketones and cyclic ketone-derived terminal olefins via asymmetric photoredox catalysis is reported. A dual catalyst system involving DPZ and a chiral phosphoric acid is effective for the transformations, leading to a wide array of valuable cyclopentylamines with high yields, ee's, and drs. Among them, elaborate modulation of the ester group of 2-aryl acrylates was shown to be effective in improving reactivity, thereby enabling the success of the transformations.

α-Amino Acids: An Emerging Versatile Synthon in Visible Light-Driven Decarboxylative Transformations.

α-Amino acids have been widely recognized as environmental-benign and non-fossil carbon sources both in biological and synthetic chemistry. In recent years, with the remarkable development of visible-light photocatalysis in organic synthesis, α-amino acid and its derivatives have received tremendous attention as radical precursors via photocatalyzed decarboxylation, thus realizing diverse aminoalkylated transformations or constructions of novel N-bearing heterocyclic motifs by taking advantage of N-atoms from α-amino acid. This review aims to provide a comprehensive update on the recent exploitation of α-amino acids in visible light photocatalysis, with particular emphasis on the types of α-amino acids employed and their distinct mechanisms applied wherein.

Development of Chinese food picture library for inducing food cravings.

Cue-induced food cravings are strong desires directed toward specific foods, usually ones with high caloric content, and can lead to overeating. However, although food cravings vary according to individual preferences for specific high-calorie food subtypes, a structured library of food craving-inducing pictures including multiple categories of high-calorie foods does not yet exist. Here, we developed and validated a picture library of Chinese foods (PLCF) consisting of five subtypes of high-calorie foods (i.e., sweets, starches, salty foods, fatty foods, and sugary drinks) to allow for more nuanced future investigations in food craving research, particularly in Chinese cultural contexts. We collected 100 food images representing these five subtypes, with four food items per subtype depicted in five high-resolution photographs each. We recruited 241 individuals with overweight or obesity to rate the food pictures based on craving, familiarity, valence, and arousal dimensions. Of these participants, 213 reported the severity of problematic eating behaviors as a clinical characteristic. Under the condition of mixing multiple subtypes of high-calorie foods, we did not observe significant differences in craving ratings for high- and low-calorie food images (p tukey > 0.05). Then, we compared each subtype of high-calorie food images to low-calorie ones, and found craving ratings were greater for the images of salty foods and sugary drinks (ps < 0.05). Furthermore, we conducted a subgroup analysis of individuals according to whether they did or did not meet the criteria for food addiction (FA) and found that greater cravings induced by the images of high-calorie food subtypes (i.e., salty foods and sugary drinks) only appeared in the subgroup that met the FA criteria. The results show that the PLCF is practical for investigating food cravings.

Catalytic Asymmetric Hydrophosphinylation of 2-Vinylazaarenes to Access P-Chiral 2-Azaaryl-Ethylphosphine Oxides.

A chiral Brønsted acid-catalysed asymmetric hydrophosphinylation of 2-vinylazaarenes by secondary phosphine oxides is described. A variety of P-chiral 2-azaaryl-ethylphosphine oxides are synthesized with high yields and ees, of which both the substituents of phosphines and azaarenes can be flexibly modulated, underscoring an exceptionally broad scope of substrates. These adducts are valuable to asymmetric metal catalysis since the resultant P-chiral tertiary phosphines from the reduction of them are verified as a kind of effective C1 -symmetric chiral 1,5-hybrid P,N-ligands. Importantly, this catalysis platform enables the generic and efficient kinetic resolution of P-chiral secondary phosphine oxides. It thus provides an expedient approach to access the enantiomers of the P-chiral tertiary phosphine oxides derived from asymmetric hydrophosphinylation, further improving the utility of the method.

Kinetic Resolution of Azaarylethynyl Tertiary Alcohols by Chiral Brønsted Acid Catalysed Phosphine-Mediated Deoxygenation.

A chiral Brønsted acid catalysed phosphine-mediated deoxygenation protocol is reported. This metal-free method provides a precise kinetic resolution platform for azaarylethynyl tertiary alcohols, which are a broad category of biologically and synthetically important azaarene derivatives. In addition to providing an efficient method for the first asymmetric preparation of these tertiary alcohols, the strategy facilitates the construction of azaaryl-functionalized allenes with good to excellent enantioselectivities. The high selectivity factors (s up to 235), broad substrate scope, and ability to convert azaaryl compounds into both chiral tertiary alcohols and allenes robustly underscore the efficiency and promising utility of this method. The practicability is further validated by the successful synthesis of deuterated allenes with high ee values and substantial incorporation of deuterium using inexpensive D2 O as the deuterium source.

Deracemization through Sequential Photoredox-Neutral and Chiral Brønsted Acid Catalysis.

Catalytic deracemization is an ideal synthetic strategy due to its formally perfect atom utilization. Asymmetric photocatalysis has been appreciated as a promising tool to accomplish this attractive reaction pattern in an economical fashion, but it remains underdeveloped. Here, we report a new platform based on photoredox-neutral catalysis, allowing efficient and modular optical enrichment of α-amino esters and other valuable analogues. Two single-electron transfer processes between the photocatalyst and the substrates serve to provide the key prochiral intermediates, and the chiral Brønsted acid catalyst mediates enantioselective protonation to reconstitute a stereogenic C-H bond. The efficiency of deracemization is determined by the enantiofacial differentiation effect during the stereocentre-forming step.

Direct SN2 or SN2X Manifold─Mechanistic Study of Ion-Pair-Catalyzed Carbon(sp3)-Carbon(sp3) Bond Formation.

Density functional theory (DFT) is used in this work to predict the mechanism for constructing congested quaternary-quaternary carbon(sp3)-carbon(sp3) bonds in a pentanidium-catalyzed substitution reaction. Computational mechanistic studies were carried out to investigate the proposed SN2X manifold, which consists of two primary elementary steps: halogen atom transfer (XAT) and subsequent SN2. For the first calculated model on original experimental substrates, XAT reaction barriers were more kinetically competitive than an SN2 pathway and connect to thermodynamically stable intermediates. Extensive computational screening modeling was then done on various substrate combinations designed to study the steric influence and to understand the mechanistic rationale, and calculations reveal that sterically congested substrates prefer the SN2X manifold over SN2. Different halides as leaving groups were also screened, and it was found that the reactivity increases in the order of I > Br > Cl > F, in agreement with the strength of C-X bonds. However, DFT modeling suggests that chlorides can be a viable substrate for the SN2X process, which should be further explored experimentally. ONIOM calculations on the full catalyst model predicted the correct stereochemical outcome, and further catalyst screening with cationic Me4N+ and K+ predicted that pentanidium is still the choice for SN2X C-C bond formation.

Kinetic and Dynamic Kinetic Resolution of Racemic Tertiary Bromides by Pentanidium-Catalyzed Phase-Transfer Azidation.

We have developed a method to afford enantiomerically enriched tertiary azides and bromides through pentanidium-catalyzed kinetic resolution (KR) of racemic tertiary bromides under base-free conditions. We found that the absence of water is crucial to attain a high selectivity factor (s). On the other hand, new experimental observations and DFT modeling led us to propose that enantioconvergent azidation of tertiary bromides proceeded through dynamic kinetic resolution (DKR). The investigations particularly identified the crucial roles of base and water in the enantioconvergent process, thus supporting the proposal that the tertiary bromide isomerizes in the presence of base and water through a SN 2X pathway.

Catalytic enantioselective alkylation of sulfenate anions to chiral heterocyclic sulfoxides using halogenated pentanidium salts.

We report halogenated pentanidiums as phase-transfer catalysts for the asymmetric alkylation of sulfenate anions to various sulfoxides with high enantioselectivities (up to 99% ee) and yields (up to 99%). This approach gives access to enantioenriched heterocyclic sulfoxides that might not be compatible with strong oxidants or organometallic reagents. Computational studies have revealed that the multiple noncovalent interactions such as halogen bonds and nonclassical hydrogen bonds are involved.

Synthesis of carbazolones and 3-acetylindoles via oxidative C-N bond formation through PIFA-mediated annulation of 2-aryl enaminones.

A series of carbazolone derivatives and 3-acetylindoles have been achieved via PIFA-mediated intramolecular cyclization of 2-aryl enaminones. This process allows the N-moiety on the side-chain to be annulated to the benzene ring via the metal-free oxidative aromatic C-N bond formation.