Electron-donor-acceptor (EDA) complex-driven regioselective vicinal and oxidative geminal functionalization of alkynes.

A visible-light-initiated electron-donor-acceptor (EDA) complex-driven regioselective vicinal and oxidative geminal thiosulfonylation of alkynes is presented. Organic thiosulfonates act as an acceptor, producing either sulfonyl (RSO2˙) or thiyl (RS˙) radicals under base and solvent switchable conditions. Simultaneous installation of three different functionalities, viz carbonyl, sulfonyl, and thiyl, takes place under one condition, while another condition leads to vicinal thiolation and sulfonylation.

Harnessing reductive BF2-complexation via Ru(II)-catalyzed N-O cleavage of isoxazoles.

Developed here is a highly fluorescent organic N,O bidentate BF2 complex from isoxazole in the presence of a Ru(II) catalyst. Herein, the complexation proceeds via a selective N-O cleavage of the isoxazole ring. The complex shows absorption (λmax,abs) in the range of 352-363 nm with an extinction coefficient (ε) in the range of 8000-64 000 M-1 cm-1, and fluorescence emission (λmax,em) in the range of 413-485 nm with a Stokes shift of 61-125 nm having quantum yield up to 33%. Apart from the solution state, the solid BF2 complex 2u exhibits absorption at 405 nm and strong fluorescence emission at 550 nm with a quantum yield of 26.9%.

Iodine-Promoted Sulfoximidation of Cinnamic Acids via Oxidative C═C Bond Cleavage.

An iodine-promoted C═C bond cleavage with concomitant decarboxylation and cross-coupling between cinnamic acids and NH-sulfoximines has been developed. This reaction proceeds via selective C═C bond cleavage, followed by decarboxylation and oxidative sulfoximidation. This metal- and base-free protocol involves dioxygen as the source of oxygen, which is facilitated by tert-butyl hydroperoxide (TBHP) as the oxidant affording N-aroylated sulfoximines with good functional group tolerance and good yields.

Electrochemical NH-Sulfoximidation with α-Keto Acids.

An electrochemical N-acylation of sulfoximine has been achieved via the coupling of α-keto acids and NH-sulfoximines. This process involves the sequential cleavage of C-C bond followed by C(sp2)-N bond formation, with the liberation of H2 and CO2 as the by-products. A library of N-aroylated sulfoximines is produced via the coupling of aroyl and sulfoximidoyl radicals by anodic oxidation under constant current electrolysis (CCE). The compatibility of the present protocol has been demonstrated by coupling of various bio-active compounds, such as NH-sulfoximine derived from (-)-borneol, L-menthol, D-glucose derivative, and some commercial drugs such as flurbiprofen, and ibuprofen. This late-stage functionalization highlights the importance of this sustainable protocol. Besides this, various control experiments and detection of H2 evolution have been performed to support the proposed mechanism.

Photo-Induced Generation of Oxygenated Quaternary Centers via EnT Enabled Singlet O2 Addition to C3-Maleimidated Quinoxaline: A Reagent-Less Approach.

Demonstrated here is an external photo-sensitizer-free (auto-sensitized) singlet oxygen-enabled solvent-dependent tertiary hydroxylation and aryl-alkyl spiro-etherification of C3-maleimidated quinoxalines. Such "reagent-less" photo-oxygenation at Csp3-H and etherification involving Csp3-H/Csp2-H are unparalleled. Possibly, the highly π-conjugated N-H tautomer allows the substrate to get excited by irradiation, and subsequently, it attains the triplet state via ISC. This excited triplet-state sensitized molecule then transfers its energy to a triplet-state oxygen (3O2) generating reactive singlet oxygen (1O2) for hydroxylation and spirocyclization depending on the solvent used. In HFIP, the generated alkoxy radical accepts a proton via HAT giving hydroxylated product. In contrast, in an aprotic PhCl it underwent a radical addition at the ortho-position of the C2 aryl to provide spiro-ether. An unprecedented orthogonal spiro-etherification was observed via the displacement of o-substitutents for ortho (-OEt, -OMe, -F, -Cl, -Br) substituted substrates. The order of ipso substitution follows the trend -OMe>-OEt>-F>-H>-Cl>-Br. Both these oxygenation reactions can be carried out with nearly equal ease using direct sunlight without the requirement of any elaborate reaction setup. Demonstration of large-scale synthesis and a few interesting transformations have also been realized. Furthermore, several insightful control experiments and quantum chemical computations were performed to unravel the mechanism.

Isothiocyanates: happy-go-lucky reagents in organic synthesis.

Owing to their unique structural features, isothiocyanates (ITCs) are a class of highly useful and inimitable reagents as the -NCS group serves both as electrophile and nucleophile in organic synthesis. ITCs share a rich legacy in organic, medicinal, and combinatorial chemistry. Compared to their oxygen equivalents, isocyanates, ITCs are easily available, less unpleasant, and somewhat less harmful to work with (mild conditions) which makes them happy-go-lucky reagents. Functionalized ITCs can finely tune the reactivity of the -NCS group and thus can be exploited in the late-stage functionalization processes. This review's primary aim is to outline ITC chemistry in the construction and derivatization of heterocycles through the lens of sustainability. For ease and brevity, the sections are divided based on reactive centers present in functionalized ITCs and modes of cyclisation. Scrutinizing their probable unexplored directions for future research studies is also addressed.

PIDA/I2-mediated photo-induced aerobic N-acylation of sulfoximines with methylarenes.

A visible-light-promoted, PIDA/I2-mediated acylation of NH-sulfoximines with methylarenes as an acyl source has been achieved. This transition metal and photosensitizer-free approach provides easy access to N-acylsulfoximines via oxidative coupling of sulfoximines with easily available methylarenes without using any peroxide source. Mechanistic investigations suggest the intermediacy of radicals and the importance of molecular oxygen.

Access to Chromenopyrrole via Tandem [3 + 2] Cycloaddition and Intramolecular C-O Coupling.

A mild and concise method for the synthesis of chromenopyrrole from 2'-hydroxychalcone is devised. The reaction proceeds via an initial [3 + 2] cycloaddition on the C═C bond of 2'-hydroxychalcone and 1,3-dipolarophile, generated in situ by the reaction of ethyl isocyanoacetate and AgOAc. This is then followed by an intramolecular C-O bond formation with the -OH group and C5-H of the in situ generated pyrrole, leading to chromenopyrroles.

Base-Promoted Synthesis of S-Arylisothiazolones via Intramolecular Dehydrative Cyclization of α-Keto-N-acylsulfoximines.

A base (Et3N)-promoted synthesis of 1,4-diarylisothiazolones from α-keto-N-acylsulfoximines has been achieved. The reaction proceeds via α-hydrogen abstraction from sulfoximine, followed by an intramolecular nucleophilic attack at the keto carbonyl to form a tert-hydroxy isothiazolone intermediate. The 1,4-substituted isothiazolone is obtained after dehydration via an E1cB path. This one-pot synthesis of isothiazolinones has a broad substrate scope, has a high atom economy, and provides products with good yields. The ΔELUMO-HOMO is calculated using Gaussian 16 at the B3LYP/6-31G(d,p) level of theory.

Electrochemical N-Aroylation of Sulfoximines by Using Benzoyl Hydrazines with H2 Generation.

Developed here is a robust electrochemical cross-coupling reaction between aroyl hydrazine and NH-sulfoximine via concomitant cleavage and formation of C(sp2 )-N bonds with the evolution of H2 and N2 as innocuous by-products. This sustainable protocol avoids the use of toxic reagents and occurs at room temperature. The reaction proceeds via the generation of an aroyl and a sulfoximidoyl radical via anodic oxidation under constant current electrolysis (CCE), affording N-aroylated sulfoximine. The strategy is applied to late-stage sulfoximidation of L-menthol, (-)-borneol, D-glucose, vitamin-E derivatives, and marketed drugs such as probenecid, ibuprofen, flurbiprofen, ciprofibrate, and sulindac. In addition, the present methodology is mild, high functional group tolerance with broad substrate scope and scalable.

Pd(II)-Catalyzed Three-Component Synthesis of Furo[2,3-d]pyrimidines from ß-Ketodinitriles, Boronic Acids, and Aldehydes.

A Pd(II)-catalyzed three-component synthesis of 2,4,6-triarylfuro[2,3-d]pyrimidines from ß-ketodinitriles, boronic acids, and aldehydes has been developed. The participation of both nitrile (-CN) groups led to the concurrent construction of furo-pyrimidine via the formation of C-C, C═C, C-O, C-N, and C═N bonds. The compounds show excellent photoluminescence properties with absorption maxima ranging from 348 to 387 nm and emission from 468 to 533 nm. The synthetic utility of the protocol was further demonstrated through a few postsynthetic manipulations.

Base-Induced Decarboxylative 1,1-Alkoxy Thiolation via Hydrothiolation of Vinylene Carbonate.

A base-mediated 1,1-difunctionalization of vinylene carbonate has been achieved using two different nucleophiles, namely, thiol and alcohol, with the assistance of air (O2). In alcoholic solvents, decarboxylation occurs at room temperature to provide a 1,1-difunctionalized product, where vinylene carbonate serves as an ethynol (C2) synthon in this three-component reaction. On the other hand, in acetonitrile, exclusive hydrothiolation occurs under the basic conditions at room temperature. This method offers a one-pot decarboxylative regioselective difunctionalization of vinylene carbonate at room temperature for the construction of α-alkoxy-ß-hydroxy sulfide.

Isoxazole as a nitrile synthon: en routes to the ortho-alkenylated isoxazole and benzonitrile with allyl sulfone catalyzed by Ru(II).

A Ru(II) catalyzed regioselective Heck-type C-H olefination of isoxazole with unactivated allyl phenyl sulfone is revealed. The solvent DCM offers dual sp2-sp2 C-H activation via an N-directed strategy, leading to ortho-olefinated isoxazoles with exclusive E-selectivity. On the other hand, in DCE solvent, isoxazole serves as the nitrile synthon and leads to o-olefinated benzonitrile. At a higher temperature (110 °C) in DCE, after the ortho-olefination Ru(II) mediated cleavage of isoxazoles delivered the nitrile functionality.

Photo-induced 1,2-thiohydroxylation of maleimide involving disulfide and singlet oxygen.

A visible light-driven di-functionalization of maleimide with disulfide and in situ-generated singlet oxygen offers selective 1,2-thiohydroxylation under additive-free conditions. Here the disulfide plays the dual role of photosensitizer and the coupling reagent. Notably, the hydroxyl functionality originates from the in situ generated singlet oxygen followed by HAT from H2O (moisture).

Synthesis of Chromenopyrroles (Azacoumestans) from Functionalized Enones and Alkyl Isocyanoacetates.

Elegant synthetic strategies for chromenopyrroles (azacoumestans) have been devised via cycloaddition of 2-hydroxychalcone/cyclic enones and alkyl isocyanoacetate, followed by lactonization. Herein, ethyl isocyanoacetate acts as a C-NH-C-C═O synthon contrary to its hitherto applications as a C-NH-C synthon. Subsequently, pentacyclic-fused pyrroles were also constructed from the o-iodo benzoyl chromenopyrroles using the Pd(II) catalyst.

Visible-light driven electron-donor-acceptor (EDA) complex-initiated synthesis of thio-functionalized pyridines.

A visible/solar-light-induced electron-donor-acceptor (EDA)-aggregated/mediated radical cyclization between (E)-2-(1,3-diarylallylidene)malononitriles and thiophenols leads to poly-functionalized pyridines. The two reacting partners form an EDA complex that absorbs light and triggers the single-electron transfer (SET) to generate a thiol radical, which undergoes addition/cyclization with dicyanodiene through the formation of C-S and C-N bonds.

Mn(I)-Catalyzed Preferential Electrophilic C3-Maleimidation in Quinoxaline Leading to Spirocyclization and Dehydrogenation of Succinimides.

A Mn(I)-catalyzed site-selective nondirected C3-maleimidation of quinoxaline is established. Herein, the electrophilic C3-metalation precedes over the o-directed strategy to access diversely substituted quinoxaline-appended succinimides. The products undergo PIFA-promoted C(sp2)-C(sp3) spirocyclization via π-electrons drifting from aryls and Selectfluor-mediated dehydrogenation of succinimide at room temperature.

Visible/solar-light-driven thiyl-radical-triggered synthesis of multi-substituted pyridines.

A light-triggered synthesis of thio-functionalized pyridines is demonstrated using γ-ketodinitriles, thiols, and eosin Y as the photocatalyst. The reaction proceeds via the selective attack on one of the cyano groups by an in situ generated thiyl radical. The reaction also proceeds with nearly equal efficiency using direct sunlight. Large-scale synthesis and a few useful synthetic transformations of the substituted pyridines are also performed.

Dearomative bis-functionalization of quinoxalines and bis-N-arylation of (benz)imidazoles via Cu(II)-mediated addition of boronic acids.

A Cu(OTf)2-mediated regioselective dearomative aryl-hydroxylation across the C(sp2)N bond of 2-aryl quinoxalines and bis-N-arylation of (benz)imidazoles were developed using aryl boronic acids. For the dearomative aryl-hydroxylation, the C-center should be electrophilic (ca. 0.08), the N-center nucleophilic (ca. -0.50), and the C(sp2)N bond polarized (Δe = 0.609).

NIS-initiated photo-induced oxidative decarboxylative sulfoximidation of cinnamic acids.

N-Iodosuccinimide catalyzed, visible-light-induced oxidative decarboxylative cross-coupling between cinnamic acids and NH-sulfoximines is presented. This strategy results in the formation of α-keto-N-acyl sulfoximines via the construction of two new CO bonds and one C-N bond. The in situ-generated N-iodosulfoximine serves as the light-absorbing species in the absence of any external photosensitizer. The keto carbonyl and amidic carbonyl oxygen in the resulting product originate from dioxygen and water respectively.