Visible-Light-Induced Acylative Pyridylation of Styrenes.

A visible-light-induced photocatalyst-free acylative pyridylation of styrenes with 4-acyl-1,4-dihydropyridines (DHPs) and 4-cyanopyridines has been described, featuring mild reaction conditions, a broad substrate scope, and good functional group tolerance. The reaction could also be performed under sunlight irradiation albeit with a slightly lower conversion. 4-Acyl-1,4-DHPs serve a dual role, acting as both a photoreductant to reduce the cyanopyridine to its radical anion intermediate and a radical precursor to produce the acyl radical. The mechanism was especially elucidated through the Hammett analysis, with the quadratic linear regression analysis by using radical dual parameters, σmb and σjj·. The findings from Hammett analysis further demonstrate that the rate-limiting step of the process is the single electron transfer between 4-acyl-1,4-DHPs and 4-cyanopyridines.

Palladium-Catalyzed Iodine Assisted Carbonylation of Indoles with ClCF2CO2Na and Alcohols.

A palladium-catalyzed iodine-assisted carbonylation reaction of indoles with readily available ClCF2CO2Na and alcohols has been developed. This protocol provides a practical and efficient approach to highly regioselective indole-3-carboxylates via a preiodination strategy of indoles. Different from classic carbonylation using toxic and difficult-to-handle carbon monoxide, this operationally simple and scalable reaction employed difluorocarbene as the carbonyl surrogate.

Access to N-Aryl (Iso)quinolones via Aryne-Induced Three-Component Coupling Reaction.

N-Aryl (iso)quinolones are of increasing interest in material and medicinal chemistry, although general routes for their provision remain underexplored, especially when compared with its N-alkyl counterparts. Herein, we report a modular and transition-metal-free, aryne-induced three-component coupling protocol that allows the facile synthesis of structurally diverse N-aryl (iso)quinolones from readily accessible halo-(iso)quinolines in the presence of water. Preliminary results highlight the applicability of our method through scale-up synthesis, downstream derivatization, and flexible synthesis involving other types of aryne precursors.

Ethynyl-B(dan) in [3+2] Cycloaddition and Larock Indole Synthesis: Synthesis of Stable Boron-Containing Heteroaromatic Compounds.

The cycloaddition of nitrile oxides with ethynyl-B(dan) (dan=naphthalene-1,8-diaminato) allowed the facile preparation of diverse isoxazolyl-B(dan) compounds, all of which displayed excellent protodeborylation-resistant properties. The dan-installation on the boron center proves vital to the high stability of the products as well as the perfect regioselectivity arising from hydrogen bond-directed orientation in the cycloaddition. The diminished boron-Lewis acidity of ethynyl-B(dan) also renders it amenable to azide-alkyne cycloaddition, Larock indole synthesis and related heteroannulations. The obtained boron-containing triazole, indoles, benzofuran and indenone exhibit sufficient resistance toward protodeborylation. Despite the commonly accepted transmetalation-inactive property derived from the diminished Lewis acidity, the synthesized heteroaryl-B(dan) compound was still found to be convertible to the oligoarene via sequential Suzuki-Miyaura coupling.

Selective S-Arylation of Sulfenamides with Arynes: Access to Sulfilimines.

Sulfilimines, the aza analogues of sulfoxides, are of increasing interest in medicinal and agrochemical research programs. However, the development of efficient routes for their synthesis has remained relatively unexplored. In this study, we report a transition metal-free, selective S-arylation reaction between sulfenamides and arynes, enabling the facile preparation of structurally diverse sulfilimines under mild and redox-neutral conditions in good yields. The application value of our method was further demonstrated by scale-up synthesis, downstream derivatization, and robustness screen.

Sulfonium-based precise alkyl transposition reactions.

S-adenosyl-L-methionine (SAM), a sulfonium-based cofactor, plays an important role in numerous biological processes as methyl donor. Inspired by the function of sulfonium motif in this nature's synthetic toolkit, we here present an aryne-activation strategy that the sulfonium intermediates in situ generated from thioethers display unique reactivity toward alkyl group transposition. Experimental and theoretical studies indicate that the reaction occurs in an intermolecular fashion where the TfO--incorporated [K(18-crown-6)] complex acts as a key promoter for this thermodynamically favored process. Next, a series of robust, easy-to-prepare sulfonium salts are designed and developed as electrophilic alkylation reagents accordingly. Both systems feature for broad scope, excellent selectivity, and simple operation. Moreover, we highlight the synthetic value through molecular editing and late-stage modification of complex scaffolds or even active pharmaceutical ingredients.

Empowering boronic acids as hydroxyl synthons for aryne induced three-component coupling reactions.

Boronic acids have become one of the most prevalent classes of reagents in modern organic synthesis, displaying various reactivity profiles via C-B bond cleavage. Herein, we describe the utilization of a readily available boronic acid as an efficient surrogate of hydroxide upon activation via fluoride complexation. The hitherto unknown aryne induced ring-opening reaction of cyclic sulfides and three-component coupling of fluoro-azaarenes are developed to exemplify the application value. Different from metal hydroxides or water, this novel hydroxy source displays mild activation conditions, great functionality tolerance and structural tunability, which shall engender a new synthetic paradigm and in a broad context offer new blueprints for organoboron chemistry. Detailed computational studies also recognize the fluoride activation mode, provide in-depth insights into the unprecedented mechanistic pathway and elucidate the reactivity difference of ArB(OH) x F y complexes, which fully support the experimental data.

Interfacial Composition of Surfactant Aggregates in the Presence of Fragrance: A Chemical Trapping Study.

In recent years, there has been increasing interest in daily-use chemical products providing a pleasant scent. The added fragrance molecules may induce microstructural transitions of surfactant aggregates, which further affect the physical and chemical properties of the products. Here, the effects of four types of aromatic alcohols (cinnamyl alcohol, phenyl ethanol, phenyl methanol and anisyl alcohol) on cetyltrimethylammonium bromide (CTAB)/KBr aggregates were studied. The combined results from rheology, dynamic light scattering, and transmission electron microscopy measurements showed that cinnamyl alcohol induced significant micellar growth, while increases in micellar growth were less obvious for the other aromatic alcohols. The changes in the interfacial molarities of water, aromatic alcohol, and bromide ions during such transitions were studied using the chemical trapping method. Transitions resulting from added cinnamyl alcohol were accompanied by significant declines in interfacial water and bromide ion molarities, and a rise in interfacial alcohol molarity. The marked decrease in interfacial water molarity was not observed in previous studies of the octanol induced formation of wormlike micelles and vesicles, indicating that a different mechanism was presented in the current system. Nuclear magnetic resonance investigation showed that π-π stacking between cinnamyl alcohols, but not cation-π interactions between alcohols and CTAB headgroups, facilitated the tight packing of alcohol molecules in CTAB aggregates and the repulsion of water from the interfacial region. The current study may provide a theoretical basis for the morphological regulation of surfactant aggregates in the presence of additives.

Cleavage and Reassembly of the C═O Bond of 2-Alkynylbenzaldehydes: A Metal-Free Access to Inden-1-ones.

A metal-free approach to inden-1-ones from 2-alkynylbenzaldehydes mediated by pyrrolidine has been developed. The reaction proceeds under mild conditions in a step- and atom-economy process by cleaving the C═O bond and constructing new C-C as well as C═O bonds. Oxygen-18 and deuterium labeling experiments revealed an aza-Petasis-Ferrier rearrangement of an intermediate 1-amino-3-methylene-dihydroisobenzofuran.

Access to Deuterated Unnatural α-Amino Acids and Peptides by Photochemical Acyl Radical Addition.

A visible-light-enabled, photocatalyst-free conjugate addition reaction of dehydroamino acids is disclosed. Employing 4-acyl-1,4-dihydropyridines as both a radical reservoir and reductant, various ß-acyl α-amino acids and their deuterated analogues were obtained in good results. Both late-stage peptide modification and stereoselective synthesis of chiral oxazolidinones are successfully achieved. The protocol is characterized by mild conditions and efficient derivatization, thus unlocking a novel blueprint to access unnatural amino acid derivatives, important building blocks with potential application in the peptidomimetic toolbox.

Visible-light-promoted photocatalyst-free alkylation and acylation of benzothiazoles.

Herein we report a protocol for the visible-light-mediated alkylation/acylation reaction of benzothiazoles. Alkyl/acyl substituted Hantzsch esters are easily prepared and rationally used as radical precursors. In the presence of BF3·Et2O and Na2S2O8, various benzothiazole derivatives were readily obtained in good yields. Our user-friendly protocol can proceed by simple irradiation with blue LEDs (λ = 465 nm) and without the assistance of external photocatalysts. The reaction is also characterized by mild conditions and scalability, thus offering an alternative and efficient tool for the synthesis of 2-functionalized benzothiazoles.

Hf(OTf)4-Catalyzed 1,6-Conjugate Addition of 2-Alkyl-azaarenes to para-Quinone Methides.

Herein we reported a Hf(OTf)4-catalyzed carbon-carbon bond formation reaction between 2-alkyl-azaarenes and para-quinone methides (p-QMs). This 1,6-conjugate addition protocol offered rapid access to a large array of triarylethane products in good yields. The catalyst loading could be reduced to 1 mol %. Studies pertinent to scale-up reaction and product derivatization were also presented.

Copper-Catalyzed Oxidative Fragmentation of Alkynes with NFSI Provides Aryl Ketones.

A copper-catalyzed oxidative cleavage reaction of alkynes using NFSI and TBHP was described. Various terminal and internal alkyne substrates were employed to render quick access to aryl ketone products in moderate to good yields. NFSI not only functioned as N-centered radical precursors but also engaged in the aryl group migration. Mechanistic studies also suggested the important role of water in the title reactions.

Simultaneous determination of interfacial molarities of an alcohol, bromide ion, and water during an alcohol induced microstructural transition: the difference between medium and long chain alcohols.

The transitions between surfactant aggregate structures are triggered by changes in chemical or physical stimulations, including addition of additives. Effects of added alcohols on aggregate morphologies correlate strongly with alcohol chain length. The local molarities of alcohol, water, and counterions in the interfacial regions play an important role in controlling the aggregate morphologies. However, direct experimental estimates of changes of interfacial alcohol molarities during alcohol induced micelle-to-vesicle transitions have never been reported. Ellipsoidal-wormlike micelle-vesicle transitions in CTAB/KBr aqueous solutions in the presence of long-chain octanol were characterized by using combined rheological, dynamic light scattering (DLS), transmission electron microscopy (TEM) and turbidity measurements. However, the transitions are absent with added butanol. The chemical trapping method (CT) was employed to understand the differences between medium- and long-chain alcohols in determining aggregate morphology. The CT method was used to estimate interfacial water, alcohol, and counterion molarities with increasing stoichiometric alcohol concentrations. With 55 mM alcohol added, the interfacial octanol molarity is 0.9 M, which is three times higher than that for butanol. With added octanol, the ellipsoidal-wormlike micelle-vesicle transition is accompanied by a concurrent sharp increase of interfacial water molarities and a decrease of interfacial counterion molarity, which is not observed with added butanol. The CT data was also employed to estimate the changes of Israelachvili's packing parameter with increasing added alcohol concentration. Our result provides critical molecular level information for understanding the morphological transitions of CTAB/additives.

Practical Synthesis of Phosphinic Amides/Phosphoramidates through Catalytic Oxidative Coupling of Amines and P(O)-H Compounds.

Herein, we report a highly efficient ZnI2 -triggered oxidative cross-coupling reaction of P(O)-H compounds and amines. This operationally simple protocol provides unprecedented generic access to phosphinic amides/phosphoramidate derivatives in good yields and short reaction time. Besides, the reaction proceeds under mild conditions, which avoids the use of hazardous reagents, and is applicable to scale-up syntheses as well as late-stage functionalization of drug molecules. The stereospecific coupling is also achieved from readily available optically enriched P(O)-H compounds.

Electrochemical Synthesis of trans-2,3-Disubstituted Aziridines via Oxidative Dehydrogenative Intramolecular C(sp3)-H Amination.

An electrochemical oxidative dehydrogenative C(sp3)-H amination reaction to construct trans-2,3-disubstituted aziridines is reported, which avoids using external oxidants and generates only hydrogen gas as the byproduct. With KI as the mediator and electrolyte, the desired aziridines were prepared in good yields in an undivided cell at room temperature. The potential value of this mild electrochemical strategy was further highlighted by the gram-scale synthesis.

Host-guest interaction enabled chiroptical photo-switching and enhanced circularly polarized luminescence.

A cyanostilbene conjugated gelator was incorporated into the cavities of cyclodextrins via the host-guest interaction and the resulting supra-gelator from γ-CyD enabled chiroptical photo-switching, while the other gels showed enhanced circularly polarized luminescences.

I2/TBHP-Mediated tandem cyclization and oxidation reaction: Facile access to 2-substituted thiazoles and benzothiazoles.

The efficient synthesis of 2-substituted thiazoles and benzothiazoles has been accomplished employing readily available cysteine esters and 2-aminobenzenethiols as N and S sources. The reaction proceeds under an I2/TBHP system and involves a one-pot tandem cyclization and oxidation sequence. A diverse range of aldehydes is amenable for this transition-metal-free protocol, which provides an alternative method to rapidly access thiazole-containing molecules.

An aryne triggered ring-opening fluorination of cyclic thioethers with potassium fluoride.

Herein, we report an aryne triggered ring-opening fluorination protocol of a great variety of saturated sulfur heterocycles. A key factor for the success is the identification of a suitable mediator. Compared to previous methods, this transition-metal free protocol employs low-cost potassium fluoride as the fluorine source. The operational simplicity and mild reaction conditions allow for the rapid synthesis of a wide range of aliphatic fluoride compounds in good yields.

Electrosynthesis of Trisubstituted 2-Oxazolines via Dehydrogenative Cyclization of ß-Amino Arylketones.

An electrochemically intramolecular functionalization of C(sp3)-H bonds with masked oxygen nucleophiles was developed. With KI as the catalyst and electrolyte, diverse trisubstituted 2-oxazolines were constructed in good to excellent yields. This newly developed electrochemical dehydrogenative approach features external oxidant-free and additive-free conditions.