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.

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.

Visible-Light-Mediated Solvent-Switched Photosensitizer-Free Synthesis of Polyfunctionalized Quinolines and Pyridines.

A solvent (2,2,2-trifluoroethanol (TFE) vs ethyl alcohol (EtOH)) switched synthesis of quinolines and pyridines is illustrated from (E)-2-(1,3-diphenylallylidene)malononitriles via a Pd(II)-catalyzed photochemical process. The active catalyst [L2Pd(0)] generated serves as an exogenous photosensitizer. The process offers predominantly Z-alkenylated quinolines and pyridines in TFE and EtOH, respectively. Furthermore, large-scale synthesis and a few interesting post-synthetic modifications have been demonstrated.

Electrochemical Amidation: Benzoyl Hydrazine/Carbazate and Amine as Coupling Partners.

An electrochemical amidation of benzoyl hydrazine/carbazate and primary/secondary amine as coupling partners via concomitant cleavage and formation of C(sp2)-N bonds has been achieved. This methodology proceeds under metal-free and exogenous oxidant-free conditions producing N2 and H2 as byproducts. Mechanistic studies reveal the in situ generations of both acyl and N-centered radicals from benzoyl hydrazines and amines. The utility of this protocol is demonstrated through a large-scale, and synthesis of bezafibrate, a hyperlipidemic drug.

Pd(II)-Catalyzed Synthesis of Furo[2,3-b]pyridines from ß-Ketodinitriles and Alkynes via Cyclization and N-H/C Annulation.

A Pd(II)-catalyzed synthesis of furopyridines has been developed from ß-ketodinitriles and alkynes via an unusual N-H/C annulation. The participation of both the nitrile groups and the concurrent construction of furan and pyridine rings through the formation of C-C, C═C, C-O, C-N, and C═N bonds are the important features. The synthetic applicability is further demonstrated through a series of postsynthetic alterations.

Metal-catalyzed reactions of organic nitriles and boronic acids to access diverse functionality.

The nitrile or cyano (-CN) group is one of the most appreciated and effective functional groups in organic synthesis, having a polar unsaturated C-N triple bond. Despite sufficient stability and being intrinsically inert, the nitrile group can be easily transformed into many other functional groups, such as amines, carboxylic acids, ketones, etc. which makes it a vital group in organic synthesis. On the other hand, despite several boronic acids having a low level of genotoxicity, they have found wide applicability in the field of organic synthesis, especially in transition metal-catalyzed cross-coupling reactions. Recently, transition-metal-catalyzed cascade additions or addition/cyclization processes of boronic acids to the nitrile group open up exciting and useful strategies to prepare a variety of functional molecules through the formation of C-C, C-N and CO bonds. Boronic acids can be added to the cyano functionality through catalytic carbometallation or through a radical cascade process to provide newer pathways for the rapid construction of various important acyclic ketones or amides, carbamidines, carbocycles and N,O-heterocycles. The present review focuses on various transition-metal-catalyzed additions of boronic acids via carbometallation or radical cascade processes using the cyano group as an acceptor.

Cu(II)-Promoted Cascade Synthesis of Fused Imidazo-Pyridine-Carbonitriles.

A Cu(II)-promoted synthesis of an aza-fused N-heterocycle having a benz-imidazopyridine scaffold is developed via an addition-cyclization reaction followed by an Ullmann-type C-N coupling between o-iodoanilines and γ-ketodinitriles. This protocol features a broad substrate scope, giving products in 32-84% yields. The compounds show excellent photoluminescence properties having two absorption maxima in the region between 270-280 and 338-350 nm and emission maxima in the range of 502-533 nm. The HOMO-LUMO energy gap of 3.49-3.57 eV was determined using Gaussian 09 at the B3LYP/6-31G (d, p) basis set level. We also demonstrated a few postsynthetic modifications.

Visible-Light-Accelerated Pd-Catalyzed Cascade Addition/Cyclization of Arylboronic Acids to γ- and ß-Ketodinitriles for the Construction of 3-Cyanopyridines and 3-Cyanopyrrole Analogues.

The one-pot synthetic strategies for 2,4,6-triarylnicotinonitriles and 2,5-diaryl-1H-pyrrole-3-carbonitriles have been accomplished via a Pd-catalyzed coupling of arylboronic acid with 2-(3-oxo-1,3-diarylpropyl)malononitrile and 2-(2-oxo-2-arylethyl)malononitrile, respectively, under mild reaction conditions, followed by intramolecular cyclization of an intermediate formed after the regeneration of the catalyst under acidic reaction conditions. The cascade reactions proceed in 1,2-dichloroethane solvent under visible-light irradiation, and the active catalyst is generated in situ in the presence of catalytic amounts of Pd(OAc)2 and 2,2'-bipyridine. The active Pd catalyst undergoes photoexcitation by the virtue of metal-to-ligand charge transfer (MLCT), and subsequent redox trans-metalation occurs with arylboronic acid, thus obviating the necessity of any exogenous photosensitizer. The targeted products, composed of a new C-C, a C-N, a C═N, and two new C═C bonds, were isolated in good yields.

Visible-Light-Induced Difunctionalization of Styrenes: Synthesis of N-Hydroxybenzimidoyl Cyanides.

A visible-light-induced synthesis of N-hydroxybenzimidoyl cyanides from aromatic terminal alkenes is achieved by using Eosin Y as an organic photoredox catalyst. The process goes via a radical pathway with successive incorporation of two nitrogen atoms, one each from tert-butyl nitrite and ammonium acetate. The final product is achieved by the concomitant installation of an oxime and a nitrile group. DFT calculation supports a biradical pathway and all the proposed steps. A few useful synthetic transformations of N-hydroxybenzimidoyl cyanide are also illustrated.

tert-Butyl Nitrite (TBN), a Multitasking Reagent in Organic Synthesis.

The upsurge interest in the development of efficient methodologies for the construction of nitrogen-containing frameworks via the use of expedient reagents have been creating a renaissance in contemporary organic chemistry. In this perspective, tertbutyl nitrite (TBN) is an emerging building block. Due to its unique structural features, it shows differential reactivity under different reaction conditions. These diverse reactivities have resulted in the construction of a diverse array of complex N-containing molecules. The primary objective of the present review is to bring the latest findings of TBN in terms of its applications in reactions (oxidation, diazotization, nitrosation, nitration, oximation, N-synthon, and miscellaneous reactions) into the limelight. For simplicity and brevity, reactions in each section are explained with the mechanism of formation and selected examples are given.

tert-Butyl Nitrite Mediated Synthesis of 1,2,4-Oxadiazol-5(4 H)-ones from Terminal Aryl Alkenes.

tert-Butyl nitrite (TBN) mediated synthesis of 3-aryl-1,2,4-oxadiazol-5(4 H)-ones has been accomplished using terminal aryl alkenes via a biradical reaction intermediate. Three consecutive sp2 C-H bond functionalizations of styrenes afforded 3-phenyl-1,2,4-oxadiazol-5(4 H)-ones via the formation of new C═N, C═O, C-O, and two C-N bonds. Both of the N atoms originate from TBN, while the carbonyl oxygen is from the water (moisture) the other oxygen from the N═O part of the TBN.

Visible-Light-Mediated Ir(III)-Catalyzed Concomitant C3 Oxidation and C2 Amination of Indoles.

A visible-light-mediated concomitant C3 oxidation and C2 amination of indoles has been achieved at room temperature using an Ir (III) photocatalyst. This reaction proceeds without an isatin intermediate via the attack of a singlet oxygen at the C3 position followed by C2 amination leading to difunctionalization of indoles.

A cascade synthesis of S-allyl benzoylcarbamothioates via Mumm-type rearrangement.

A catalyst and solvent free synthesis of S-allyl benzoylcarbamothioates has been achieved from the in situ generated benzoylcarbonimidothioates obtained by reacting MBH alcohols with aroyl isothiocyanates. An intramolecular thia-Michael addition of the in situ generated adduct triggers a Mumm-type rearrangement leading to a stereoselective synthesis of highly functionalised S-allyl benzoylcarbamothioates.

Microwave-Assisted Cascade Strategy for the Synthesis of Indolo[2,3-b]quinolines from 2-(Phenylethynyl)anilines and Aryl Isothiocynates.

The in situ generated o-alkynylthioureas obtain by reacting 2-(phenylethynyl)anilines and aryl isothiocynates undergo efficient cascade cyclization in the presence of Ag2CO3 to form indoloquinolines under microwave heating. The present tandem process allows the generation of a variety of indolo[2,3-b]quinolines derivatives in good to moderate yields with a wide functional group tolerance.