The 50 most-cited articles in The Journal of Organic Chemistry, 2023

Sulfur alkylation of N -acyl sulfenamides with alkyl halides provides sulfilimines in 47% to 98% yields. A broad scope was established with a variety of aryl and alkyl sulfenamides, including for different N -acyl groups. Alkyl halides with different steric and electronic properties were effective inputs, including methyl, primary, secondary, benzyl, and propargyl halides. A proof-of-concept asymmetric phase-transfer alkylation was also demonstrated. A sulfilimine product was readily converted to an N -acyl and to a free sulfoximine, which represent important motifs in medicinal chemistry.

-halosuccinimides (NXS) as the halogenating reagents has been developed. This reaction is carried out at room temperature under simple conditions without relying on metal reagents, photochemistry, or electrochemistry, providing a fast and efficient route to synthesize a wide variety of 4-halomethyl-2-azaspiro[4.5]decanes with satisfactory yields. The approach is further highlighted through gram-scale synthesis and diverse transformations of the spiro products.

Carbon monoxide is a cheap and abundant C1 building block that can be readily incorporated into organic molecules to rapidly build structural complexity. In this Perspective, we outline several recent (since 2015) examples of palladium-catalyzed carbonylations in streamlining complex natural product total synthesis and highlight the strategic importance of these carbonylation reactions in the corresponding synthesis. The selected examples include spinosyn A, callyspongiolide, perseanol, schizozygane alkaloids, cephanolides, and bisdehydroneostemoninine and related stemona alkaloids. We also provide our perspective about the recent advancements and future developments of palladium-catalyzed carbonylations.

Herein, we present a practical strategy for the direct construction of structurally diverse trifluoromethyl carbinol-containing compounds, especially CF 3 -substituted tertiary alcohol with chromone derivatives from easily available o -hydroxyaryl enaminones and trifluoroacetaldehyde/ketone derivatives under metal-free conditions. This reaction features a broad substrate scope with good yields and is easily scaled up. Notably, a one-pot in two-steps reaction of obtained products with amidines is also developed to provide a series of multi-substituted pyrimidine derivatives bearing two unique hydroxyls and one trifluoromethyl containing functional units.

The catalytic cycloaddition of CO 2 to epoxides to afford cyclic carbonates as useful monomers, intermediates, solvents, and additives is a continuously growing field of investigation as a way to carry out the atom-economic conversion of CO 2 to value-added products. Metal-free organocatalytic compounds are attractive systems among various catalysts for such transformations because they are inexpensive, nontoxic, and readily available. Herein, we highlight and discuss key advances in the development of polymer-based organocatalytic materials that match these requirements of affordability and availability by considering their synthetic routes, the monomers, and the supports employed. The discussion is organized according to the number (monofunctional versus bifunctional materials) and type of catalytically active moieties, including both halide-based and halide-free systems. Two general synthetic approaches are identified based on the postsynthetic functionalization of polymeric supports or the copolymerization of monomers bearing catalytically active moieties. After a review of the…

-arylation of sulfenamides with diaryliodonium salts for the synthesis of sulfilimines is developed. The reaction proceeds smoothly under transition-metal-free and air conditions, giving rapid access to sulfilimines in good to excellent yields via selective S-C bond formation. This protocol is scalable and exhibits a broad substrate scope, good functional group tolerance, and excellent chemoselectivity.

Two types of electrophilic trifluoromethylthiolating reagents were developed in the past 10 years in our laboratory. The development of the first type of reagent, trifluoromethanesulfenate I, which is highly reactive toward a variety of nucleophiles, was based on an unexpected discovery in the initial design for the development of an electrophilic trifluoromethylthiolating reagent with a hypervalent iodine skeleton. A structure–activity study disclosed that α-cumyl trifluoromethanesulfenate (reagent II) without the iodo substituent is equally effective. Subsequent derivatization let us develop an α-cumyl bromodifluoromethanesulfenate III that could be used for the preparation of [ 18 F]ArSCF 3 . To remediate the low reactivity of the type I electrophilic trifluoromethylthiolating reagent for Friedel–Crafts trifluoromethylthiolation of electron-rich (hetero)arenes, we designed and prepared N -trifluoromethylthiosaccharin IV, which exhibits broad reactivity toward various nucleophiles, including electron-rich arenes. A comparison of the structure of N -trifluoromethylthiosaccharin IV…

A novel protocol for synthesizing N -alkyl indoles from readily available N -nitrosoanilines and iodonium ylides through the rhodium(III)-catalyzed C–H bond activation/intramolecular cyclization reaction has been described. This strategy employs nitroso as a traceless directing group. The transformation features powerful reactivity, tolerates various functional groups, and proceeds with moderate yields under mild reaction conditions, providing a straightforward approach to access structurally diverse and valuable N -alkyl indole derivatives.

The sulfinamidines as aza analogues of sulfinamides received limited attention from both organic chemists and pharmaceutical chemists. Herein, we present a tandem oxidative/nucleophilic substitution approach for the synthesis of sulfinamidines in high yield (up to 98%). This cascade reaction method is enabled by N-bromosuccinimide (NBS) as an oxidant and diverse readily available amines as nucleophiles without any additives or catalysts. Notably, this method is highly time-economical, safe to operate, and easy to scale up and has excellent functional group compatibility.

We conceptualized a novel disconnection approach for the synthesis of fused tetrahydroquinolines that exploits a visible light-mediated radical (4 + 2) annulation between alkyl N -(acyloxy)phthalimides and N -substituted maleimides in the presence of DIPEA as an additive. The reaction proceeds through the formation of a photoactivated electron donor–acceptor complex between alkyl NHPI esters and DIPEA, and the final tetrahydroquinolines were obtained in a complete regioselective fashion. The methodology features a broad scope and good functional group tolerance and operates under metal- and catalyst-free reaction conditions. Detailed mechanistic investigations including density functional theory studies provide insight into the reaction pathway.

4-Membered ring heterocycles oxetanes and azetidines offer exciting potential as small polar molecular motifs in medicinal chemistry but require further methods for their incorporation. Photoredox catalysis has emerged as a powerful method for the mild generation of alkyl radicals for C–C bond-forming reactions. However, the reactivity of radicals on strained rings is not well understood and there are few studies that address this question systematically. Furthermore, examples that use tertiary and benzylic radicals are rare, and their reactivity is challenging to harness and direct towards productive reaction pathways. This work develops a radical functionalization of benzylic oxetanes and azetidines using visible light photoredox catalysis to prepare 3-aryl-3-alkyl substituted derivatives and assesses the influence of ring strain on the reactivity of medicinally important small-ring radicals. 3-Aryl-3-carboxylic acid oxetanes and azetidines are suitable precur- sors for the formation of tertiary benzylic oxetane/azetidine radicals with loss of CO2 and subsequent conjugate addition…

Rongalite has been used as a cheap and efficient carbon synthon for the synthesis of divergent N-heteroaromatics, including different pyridines and quinolines. The selective synthesis of different products can be achieved by employing enaminones or enaminones/anilines as reaction partners. In addition, compared with the reaction using conventional aldehyde synthons, rongalite displays an evident advantage in providing products with considerably higher product yields under milder conditions. The GC-MS analysis of the reaction process has been performed to probe the possible reaction mechanism.

A Ru(II)-catalyzed efficient and selective N -alkylation of amines by C1–C10 aliphatic alcohols is reported. The catalyst [Ru(L 1a )(PPh 3 )Cl 2 ] ( 1a ) bearing a tridentate redox-active azo-aromatic pincer, 2-((4-chlorophenyl)diazenyl)-1,10-phenanthroline ( L 1a ) is air-stable, easy to prepare, and showed wide functional group tolerance requiring only 1.0 mol % (for N -methylation and N -ethylation) and 0.1 mol % of catalyst loading for N -alkylation with C3–C10 alcohols. A wide array of N -methylated, N -ethylated, and N -alkylated amines were prepared in moderate to good yields via direct coupling of amines and alcohols. 1a efficiently catalyzes the N -alkylation of diamines selectively. It is even suitable for synthesizing N -alkylated diamines using (aliphatic) diols producing the tumor-active drug molecule MSX-122 in moderate yield. 1a showed excellent chemo-selectivity during the N -alkylation using oleyl alcohol and monoterpenoid β-citronellol. Control experiments and mechanistic investigations revealed that the 1a -catalyzed N -alkylation reactions proceed via a borrowing…

In the quest to synthesize high-performing insensitive high-energy density materials (HEDMs), the main challenge is establishing an equilibrium between energy and stability. For this purpose, we explored 4-hydroxy-3,5-dinitropyrazole- and tetrazole-based energetic scaffolds connected via a N -methylene-C bridge. The hydroxy functionality between nitro groups on the pyrazole ring promotes physical stability via inter- and intramolecular hydrogen bonding and contributes to oxygen balance, supporting better energetic performance. Due to two acidic sites (O H and N H ) with different reactivities, a series of monocationic and dicationic salts were synthesized, and their overall performance was compared. All compounds synthesized in this study have high physical stability with impact sensitivity >40 J and friction sensitivity >360 N. Monocationic salts were generally found to have better thermal stability with respect to their corresponding dicationic energetic salts, which showed better energetic performance. The salt formation strategy effectively improved the thermal stability of 2 (…

A commercially available and versatile dehydrative amidation catalyst, featuring a thianthrene boron acid structure, has been developed. The catalyst shows high catalytic activity to both aliphatic and less reactive aromatic carboxylic acid substrates, including several bioactive or clinical molecules with a carboxylic acid group.

A visible-light-induced cross-dehydrogenative methodology has been developed for the regioselective sulfenylation of pyrazolo[1,5- a ]pyrimidine derivatives. Rose bengal, blue LEDs, KI, K 2 S 2 O 8, and DMSO are all essential for this photocatalytic transformation. The protocol is applicable for the synthesis of a library of 3-(aryl/heteroaryl thio)pyrazolo[1,5- a ]pyrimidine derivatives with broad functionalities. The selectivity and scalability of the methodology have been also demonstrated. Moreover, the efficiency of this strategy for sulfenylation of pyrazoles, indole, imidazoheterocycles, and 4-hydroxy coumarin has been proven. The mechanistic investigation revealed the radical-based mechanism and formation of diaryl disulfide as a key intermediate for this cross-dehydrogenative coupling reaction.

An efficient, catalyst- and additive-free, visible-light-driven radical C3–H alkylation of quinoxalin-2(1 H )-one derivatives has been developed. This reaction utilizes alkyl-NHP-esters as an alkyl radical donor and quinoxalin-2(1 H )-one derivatives as an alkyl radical acceptor. The operationally simple protocol works under mild reaction conditions and tolerates a variety of functional groups. Furthermore, the synthetic utility of the methodology was successfully implemented for synthesizing biologically relevant C3-alkyl substituted quinoxalin-2(1 H )-one derivatives

Magnetically induced ring currents are a conventional tool for the characterization of aromaticity. Dia- and paratropic currents are thought to be associated with stabilization (aromaticity) and destabilization (antiaromaticity), respectively. In the present work, I have questioned the validity of the paratropic currents as a measure of antiaromaticity among monocyclic hydrocarbons. I have shown that while reduced/oxidized radical ions of hydrocarbons sustain strong paratropic currents, they often gain extra stabilization via cyclic conjugation compared to their acyclic counterparts.

Electrochemical oxidation of alkene difunctionalization with simultaneous construction of C–Se and C–S bonds is reported. The products of β-selenylethyl dithiocarbamates are obtained with CS 2, amines, alkenes, and diphenyl diselenides in the absence of any oxidant or metal. Furthermore, the transformation is compatible with various groups. In the preliminary mechanism studies, we propose three possible pathways.

A straightforward and efficient electrochemical method for regioselective C( sp 2 )–H selenylation and sulfenylation of substituted 2-amino-1,4-naphthoquinones has been unearthed. This oxidative cross -coupling reaction avoids using transition metal catalysts, oxidants, and high temperatures. The other notable advantages of this protocol are the tolerance of diverse functional groups, mild reaction conditions at ambient temperature, energy efficiency, good to excellent yields, short reaction times (in minutes), gram-scale applicability, and eco-friendliness.

We describe a visible-light photoredox-catalyzed alkylation/arylative cyclization of N -acrylamides─from 2-arylindoles, 2-arylbenzimidazoles, or N -substituted anilines─with ketone-derived dihydroquinazolinones, accessing indolo- and benzimidazolo[2,1- a ]isoquinolines or 2-oxindoles. The consecutive incorporation of alkyl- and aryl-carbogenic motifs across a C=C bond via formal cleavage of ketone α-C–C and arene C–H bonds leads to the formation of five- and six-membered rings, with an all-carbon quaternary stereocenter. This dicarbofunctionalization elaborates aromatization-driven radical C–C functionalization of unactivated aliphatic ketones to construct diverse cyclic structures with functionality tolerance.

A simple and practical electron donor–acceptor (EDA) strategy to synthesize various 3-alkylated coumarins from easily available coumarins and naturally abundant carboxylic acids under photocatalyst-, oxidant-, and additive-free and mild conditions is reported. Using Na 2 S as the catalytic electron donor, a series of primary, secondary, and tertiary carbon radicals can be efficiently generated, and the EDA complex can be regenerated without an alkaline additive.

A general and efficient method for the synthesis of various selanyl phenanthrenes/polycyclic heteroaromatics through the electrophilic annulation of 2-alkynyl biaryls with diorganyl diselenides under metal-free and mild conditions was established. The sulfanyl phenanthrene was also obtained in moderate yields.

A binary catalytic system comprising tetrahydroxydiboron and tetrabutylammonium iodide (TBAI) was used to catalyze the cycloaddition of carbon dioxide (CO 2 ) with epoxides. The tetrahydroxydiboron catalyst (9 mol %), in combination with the use of TBAI (13.5 mol %) as a nucleophile, is capable of catalyzing the cycloaddition of CO 2 with various terminal epoxides under room temperature and a CO 2 balloon. In addition, a range of internal epoxides, including sterically hindered bicyclic epoxides and vegetable oil-based epoxides, were suitable for the catalytic system, affording a series of cyclic carbonates in moderate to high yields. The tetrahydroxydiboron/TBAI cooperative catalytic mechanism was elucidated using Fourier transform infrared spectroscopy, nuclear magnetic resonance, and electrospray ionization-high-resolution mass spectrometry. Results reveal that the tetrahydroxydiboron catalyst exhibits dual effects, activating both CO 2 and epoxides; initially, it underwent the insertion of CO 2 to form a boron–CO 2 adduct and subsequently activated the epoxides through…

In this study, we present a novel, efficient method for the oxidative amination of sulfenamides using diacetoxyiodobenzene (PhI(OAc) 2 ) and amines under basic conditions. This innovative technique streamlines the synthesis of sulfinamidines under mild, metal-free conditions, achieving outstanding yields of up to 99%. Furthermore, we propose possible pathways that elucidate the observed molecular sequence of events in this reaction. This cutting-edge approach not only advances the synthesis of valuable sulfinamidine compounds but also expands the synthetic toolbox available to chemists, paving the way for future discoveries in organic synthesis and potential applications in medicinal chemistry.

as an oxidant, the present study reports a new photochemical protocol that enables efficient aerobic oxidation of various benzyl alcohols to the corresponding aldehydes or ketones in excellent yields under mild reaction conditions. The catalyst system presents good functional-group tolerance and exquisite chemoselectivity, which also can easily be scaled-up to gram scale. Moreover, the methodological applications in practical synthesis of several organic molecules and the primary reaction mechanism were also discussed.

A visible-light-driven deoxygenative cross-coupling of alcohols with sulfonyl oxime ethers has been developed by using xanthate salts as alcohol-activating groups. Upon convenient generation and direct photoexcitation of xanthate anions, a broad range of alcohols including primary ones can efficiently undergo this transformation to afford diverse oxime ethers and derivatives. This one-pot protocol features mild conditions, broad substrate scope, and late-stage applicability, without the need for any external photocatalysts or electron donor-acceptor complex formation.

A facile cascade reaction for the site selective synthesis of 2-cyanochromones is described. By using simple o -hydroxyphenyl enaminones and potassium ferrocyanide trihydrate (K 4 [Fe(CN) 6 ] 3 ·3H 2 O) as starting materials and I 2 /AlCl 3 as promoters, the products are furnished via tandem chromone ring formation and C–H cyanation. The in situ formation of 3-iodochromone and a formal 1,2-hydrogen atom transfer (HAT) process account for the unconventional site selectivity. In addition, the synthesis of 2-cyanoquinolin-4-one has been realized by employing corresponding 2-aminophenyl enaminone as substrate.

Catalytic reduction reactions using methanol as a transfer hydrogenating agent is gaining significant attention because this simple alcohol is inexpensive and produced on a bulk scale. Herein, we report the catalytic utilization of methanol as a hydrogen source for the reduction of different functional organic compounds such as nitroarenes, olefins, and carbonyl compounds. The key to the success of this transformation is the use of a commercially available Pt/C catalyst, which enabled the transfer hydrogenation of a series of simple and functionalized nitroarenes-to-anilines, alkenes-to-alkanes, and aldehydes-to-alcohols using methanol as both the solvent and hydrogen donor. The practicability of this Pt-based protocol is showcased by demonstrating catalyst recycling and reusability as well as reaction upscaling. In addition, the Pt/C catalytic system was also adaptable for the N -methylation and N -alkylation of anilines via the borrowing hydrogen process. This work provides a simple and flexible approach to prepare a variety of value-added products from readily available methanol,…

In 1965, Woodward and Hoffmann proposed a theory to predict the stereochemistry of electrocyclic reactions, which, after expansion and generalization, became known as the Woodward-Hoffmann Rules. Subsequently, Longuet-Higgins and Abrahamson used correlation diagrams to propose that the stereoselectivity of electrocyclizations could be explained by the correlation of reactant and product orbitals with the same symmetry. Immediately thereafter, Hoffmann and Woodward applied correlation diagrams to explain the mechanism of cycloadditions. We describe these discoveries and their evolution. We now report an investigation of various electrocyclic reactions using DFT and CASSCF. We track the frontier molecular orbitals along the intrinsic reaction coordinate and modeled trajectories and examine the correlation between HOMO and LUMO for thermally forbidden systems. We also investigate the electrocyclizations of several highly polarized systems for which the Houk group had predicted that donor-acceptor substitution can induce zwitterionic character, thereby providing low-energy pathways for…

A direct arylsulfonylation of β,γ-unsaturated hydrazones method, in which sulfonated pyrazolines are accessed by a three-component reaction of β,γ-unsaturated hydrazones, DABSO, and aryldiazonium tetrafluoroborates, has been developed without external oxidants or catalysts. This transformation is triggered by the formation of arylsulfonyl radicals in situ from the reaction of aryldiazonium tetrafluoroborates and DABSO, and is enabled by controllable generation of C center radical, in which DABSO was utilized as the sulfone source and an oxidant in this radical-mediated cascaded reaction. A wide range of substrates can be applied in this process to afford pyrazolines in good yield, and it is amenable for gram-scale synthesis.

Diverse functionalized dihydrobenzofuran spiro-indanedione-oxindole scaffolds were conveniently synthesized by base-promoted cyclization reaction of Morita–Baylis–Hillman (MBH) carbonates of isatins and 2-( o -hydroxybenzylidene)-1,3-indanediones. The two diastereomeric dispiro[indene-2,1′-cyclopenta[ b ]benzofuran-2′,3″’-indolines] could be selectively synthesized by using DABCO or DMAP as a base promoter. More importantly, DABCO or DMAP facilitated the annulation reaction of MBH formates of isatins and 2-( o -hydroxybenzylidene)-1,3-indanediones selectively, resulting in spiro[cyclopropa[ c ]chromene-1,2′-indene]-1′,3′-diones or dispiro[indene-2,1′-cyclopenta[ b ]benzofuran-2′,3″’-indolines]. Additionally, a similar reaction with MBH maleimides of isatins afforded dispiro[indene-2,5′-benzofuro[2′,3′:1,5]cyclopenta[1,2- c ]pyrrole-4′,3″’-indolines] in high yields and with high diastereoselectivity.

Herein, we report a blue-light-driven amination of C( sp 2 )–H bond of naphthoquinones and quinones with the N–H bond of primary and secondary amines for the synthesis of 2-amino-naphthoquinones and 2-amino-quinones. The coupling of naphthoquinones with a wide array of aliphatic, aromatic, chiral, primary, and secondary amines having electron donating (−CH 3, −OCH 3, −SCH 3 ), withdrawing (−F, −Cl, −Br, −I), and CO 2 H, −OH, −NH 2 groups with acidic protons selectively occurred to afford C–N coupled 2-amino-naphthoquinones in 60–99% yields and hydrogen gas as a byproduct in methanol solvent without using any additional reagents, additives, and oxidant under the blue light irradiation. Mechanistic insight by DFT computation, controlled experiments, kinetic isotopic effect, and substitution effect of the substrates suggest that the reaction proceeds by radical pathway in which naphthoquinone forms a highly oxidizing naphthoquinonyl biradical upon irradiation of blue light (457 nm). Consequently, electron transfer from electron-rich amine to an oxidizing naphthoquinonyl biradical leads…

A three-component oxychalcogenation reaction, from alkenes, diselenides/thiophenols, and H 2 O/alcohols, has been realized herein. Tetrabutylammonium tribromide (TBATB) and dimethylsulfoxide (DMSO) are utilized as the catalyst and the terminal oxidant, respectively, to enable this difunctionalization transformation. The metal-free reaction system shows good functional group compatibility, providing a unified and practical approach to access β-hydroxyl or β-alkoxy organochalcogenides.

A visible-light-induced efficient methodology has been developed for the C–H selenylation of pyrazolo[1,5- a ]pyrimidine derivatives employing erythrosine B as the photocatalyst. This is the first report on the regioselective selenylation of pyrazolo[1,5- a ]pyrimidines. The efficiency of this methodology for the selenylation of different electron-rich heterocycles like pyrazole, indole, imidazo[1,2- a ]pyridine, imidazo[2,1- b ]thiazole, and 4-(phenylamino)-2 H -chromen-2-one has been also demonstrated. The exploration of erythrosine B as a photocatalyst with a simple and mild procedure, wide substrate scope, and practical applicability and the employment of eco-friendly energy, oxidant, and solvent are the attractive characteristics of this methodology.

Herein, we report a Zn(II)-catalyzed solvent-free sustainable synthesis of tri- and tetra-substituted pyridines using alcohols as the primary feedstock and NH 4 OAc as the nitrogen source. Using a well-defined air-stable Zn(II)-catalyst, 1a, featuring a redox-active tridentate azo-aromatic pincer, 2-((4-chlorophenyl)diazenyl)-1,10-phenanthroline ( L a ), a wide variety of unsymmetrical 2,4,6-substituted pyridines were prepared by three-component coupling of primary and secondary alcohols with NH 4 OAc. Catalyst 1a is equally compatible with the four-component coupling. Unsymmetrical 2,4,6-substituted pyridines were also prepared via a four-component coupling of a primary alcohol with two different secondary alcohols and NH 4 OAc. A series of tetra-substituted pyridines were prepared up to 67% yield by coupling primary and secondary alcohols with 1-phenylpropan-1-one or 1,2-diphenylethan-1-one and NH 4 OAc. The 1a -catalyzed reactions also proceeded efficiently upon replacing the secondary alcohols with the corresponding ketones, producing the desired tri- and tetra-substituted…

A photoredox-catalyzed intermolecular tandem sulfonamination/cyclization of enaminones was realized by using N -aminopyridinium salts as the sulfonaminated reagents without transition-metal catalysts or bases. The reaction exhibits a broad scope and good functional group tolerance, good yields, and regioselectivity. Preliminary mechanistic studies support the radical property of the reaction and the involvement of N -centered radical intermediates.

Conversion of alcohols into corresponding carbonyl compounds through an oxidation reaction with high conversion and selectivity simultaneously under mild conditions still remains a great challenge. Herein, a cost-effective and highly efficient photocatalytic protocol for selective oxidation of alcohols was developed using CsPbBr 3 perovskite as a heterogeneous photocatalyst, which afforded aldehydes/ketones exclusively with a yield of 99% at ambient temperature under an air atmosphere. Moreover, the photocatalyst can be recycled at least 5 times without a significant decrease in catalytic activity. The detailed reaction mechanism was investigated by a series of quenching experiments, including Stern–Volmer experiments and electron paramagnetic resonance spectroscopy analysis as well as DFT calculations.

Herein, we reported a facile and readily accessible visible-light-driven photocatalytic protocol to induce oxidative cleavage of C═C bonds to corresponding carbonyls using CsPbBr 3 nanocrystals as photocatalysts. This catalytic system was applicable to a wide range of terminal and internal alkenes. Detailed mechanism studies indicated that a single-electron transfer (SET) process was involved in this transformation, wherein the superoxide radical (O 2 •– ) and photogenerated holes played crucial roles. Additionally, DFT calculations revealed that the reaction was initiated by the addition of O 2 •– to the terminal carbon atom of the C═C bond and completed by releasing one molecular formaldehyde by the formed [2 + 2] intermediate; the latter conversion was a rate-determining process.

An efficient photocatalytic oxidation of benzylic C(sp 3 )–H bonds to ketones, esters, and amides has been developed using NBS as a metal-free photocatalyst and O 2 as an oxidant. A variety of synthetically and biologically valuable compounds are assembled in moderate to excellent yields. The synthetic utility of this approach has been demonstrated by gram-scale experiments. A possible free radical mechanism was proposed to rationalize the reaction procedure.

A majority of known and newly synthesized energetic materials comprise polynitrogen or nitrogen–oxygen heterocycles with various explosophores. However, available structural combinations of these organic scaffolds are finite and are about to reach their limits. Herein, we present the design and synthesis of a series of sulfur-containing polyazole structures comprising 1,3,4-thiadiazole and furazan rings linked by C–C bonds and enriched with energetic nitro and azo functionalities. In terms of detonation performance, all synthesized 1,3,4-thiadiazole-furazan assemblies ( D = 7.7–7.9 km s –1; P = 26–28 GPa) lie between the powerful explosive TATB ( D = 8.0 km s –1; P = 31 GPa) and melt-cast material TNT ( D = 6.9 km s –1; P = 23 GPa). In the synthesized series, azo-bridged derivative 5 seems to be most practically interesting, as it combines a relatively high energetic performance ( D = 7.9 km s –1; P = 28 GPa), a very high thermal stability (271 °C), and insensitivity to friction. By these functional properties, 5 outperforms the benchmark heat-resistant explosive hexanitrostilbene…

an electrochemical Ritter-type reaction is developed. The reaction demonstrates simpler and milder reaction conditions over the existing methods without extra mediator. Moderate to excellent yields up to 94% of the desired amide products were obtained with a broad substrate scope. The removal of the Ac group by a simple step can afford NH-free benzylic amines, providing a suitable approach for the late-stage functionalization of bioactive molecules.

This study investigates the photoinduced C–X borylation reaction of aryl halides by forming a halogen-bonding (XB) complex using 2-naphthol as an XB acceptor. The method is chemoselective and broadly functional group tolerant and provides concise access to corresponding boronate esters. Mechanistic studies reveal that forming the XB complex between aryl halide and naphthol acts as an electron donor–acceptor complex to furnish aryl radicals through photoinduced electron transfer.

Herein, we report azo-benzimidazole containing cobalt complexes ( 1 – 3 ) for alcohol dehydrogenation-triggered C3-alkylation of indoles. In complexes 1–3, ligands are redox noninnocent and showed facile irreversible L/L • reduction followed by Co(II)/Co(I) reduction in close-lying potentials. Taking advantage of facile redox events in 1 – 3, the first aerial dehydrogenation of alcohols to their corresponding carbonyl compounds is explored. Subsequently, C3-alkylation of indole was studied using alcohols as the alkylating agents. The developed catalytic protocol was found to be efficient and very selective. It has a broad substrate scope and good functional group tolerance. As far as we are aware, it is the first homogeneous cobalt catalyst for C3-alkylation of indole using alcohol as the alkylating agent. Detailed mechanistic studies, including a deuterium labeling experiment, have suggested a borrowing hydrogen method for the C3-alkylation of indole. The coordinated ligand, cooperatively with the Co(II)/Co(I) redox couple, oxidized the coordinated alkoxide in a radical pathway to…

An air-tolerant mechanoredox/nickel cocatalyzed cross electrophile coupling of benzotriazinones with alkyl (pseudo)halides is developed by liquid-assisting grinding in the presence of manganese powders and strontium titanate as a reductant and a cocatalyst, respectively. Mechanical activation of metal surfaces via ball milling eliminates the chemical activator for manganese, while mechanoredox cocatalysis of strontium titanate remarkably improves the aryl/alkyl cross electrophile coupling via piezoelectricity-mediated radical generation from alkyl halides. Both benzotriazinones and alkyl (pseudo)halides display reactivities in the mechanoredox/nickel cocatalysis different from those of conventional thermal chemistry in solution. The scope of the reaction is demonstrated with 26 examples, showing a high chemoselectivity of bromides vs chlorides.

Azopyrazoles are an emerging class of photoswitches, whereas analogous azoimidazole-based switches are unable to draw much attention because of their short cis half-lives, poor cis–trans photoreversion yields, and toxic ultraviolet (UV) light-assisted isomerization. A series of 24 various aryl-substituted N -methyl-2-arylazoimidazoles were synthesized, and their photoswitching performances and cis–trans isomerization kinetics were thoroughly investigated experimentally and theoretically. Para -π-donor-substituted azoimidazoles with highly twisted T-shaped cis conformations showed nearly complete bidirectional photoswitching, whereas di- o -substituted switches exhibited very long cis half-lives (days–years) with nearly ideal T-shaped conformations. This study demonstrates how the electron density in the aryl ring affects cis half-life and cis–trans photoreversion via twisting of the NNAr dihedral angle that can be used as a predictive metric for envisaging and tuning the likely switching performance and half-life of any given 2-arylazoimidazole. By applying this tool, two…

A new Pd(II)-catalyzed annulation/iododifluoromethylation of enynones has been developed for the synthesis of versatile 1-indanones with moderate to good yields (26 examples). The present strategy enabled the concomitant incorporation of two important difluoroalkyl and iodo functionalities into 1-indenone skeletons with ( E )-stereoselectivity. The mechanistic pathway was proposed, consisting of the difluoroalkyl radical-triggered α,β-conjugated addition/5- exo -dig cyclization/metal radical cross-coupling/reductive elimination cascade.

A highly selective and divergent synthesis which enabled access to various complex compounds is highly attractive in organic synthesis and medicinal chemistry. Herein, we developed an effective method for divergent synthesis of highly substituted tetrahydroquinolines via Lewis base catalyzed switchable annulations of Morita-Baylis-Hillman carbonates with activated olefins. The reaction displayed switchable [4 + 2] or [3 + 2] annulations via catalyst or substrate control, providing a diverse range of architectures which contained highly substituted tetrahydroquinolines or cyclopentenes with three contiguous stereocenters bearing a quaternary carbon center in high yields with excellent diastereoselectivities and regioselectivities. Furthermore, synthetic utility of this strategy was further highlighted by gram-scale experiments and simple transformations of the products.

Azoles and organoselenium compounds are pharmacologically important scaffolds in medicinal chemistry and natural products. We developed an efficient regioselective electrochemical aminoselenation reaction of 1,3-dienes, azoles, and diselenide derivatives to access selenium-containing allylazoles skeletons. This protocol is more economical and environmentally friendly and features a broad substrate scope; pyrazole, triazole, and tetrazolium were all tolerated under the standard conditions, which could be applied to the expedient synthesis of bioactive molecules and in the pharmaceutical industry.

Sacrificial additives are commonly employed in photoredox catalysis as a convenient source of electrons, but what occurs after electron transfer is often overlooked. Tertiary alkylamines initially form radical cations following electron transfer, which readily deprotonate to form strongly reducing, neutral α-amino radicals. Similarly, the oxalate radical anion (C 2 O 4 •– ) rapidly decomposes to form CO 2 •– ( E 0 ≈ −2.2 V vs SCE). We show that not only are these reactive intermediates formed under photoredox conditions, but they can also impact the desired photochemistry, both positively and negatively. Photoredox systems using oxalate as an electron donor are able to engage substrates with greater energy demands, extending reactivity past the energy limits of single and multiphoton transition metal catalysts. Furthermore, oxalate offers better chemoselectivity than the commonly employed triethylamine when reducing substrates with moderate energy requirements.