Expedient radical phosphonylations via ligand to metal charge transfer on bismuth.

Bismuth, in spite of its low cost and low toxicity, has found limited application in organic synthesis. Although the photoactivity of Bi(iii) salts has been well studied, this has not been effectively exploited in photocatalysis. To date, only a single report exists for the Bi-based photocatalysis, wherein carbon centered radicals were generated using ligand to metal charge transfer (LMCT) on bismuth. In this regard, expanding the horizon of bismuth LMCT catalysis for the generation of heteroatom centered radicals, we hereby report an efficient radical phosphonylation using BiCl3 as the LMCT catalyst. Phosphonyl radicals generated via visible-light induced LMCT of BiCl3 were subjected to a variety of transformations like alkylation, amination, alkynylation and cascade cyclizations. The catalytic system tolerated a wide range of substrate classes, delivering excellent yields of the scaffolds. The reactions were scalable and required low catalytic loading of bismuth. Detailed mechanistic studies were carried out to probe the reaction mechanism. Diverse radical phosphonylations leading to the formation of sp3-C-P, sp2-C-P, sp-C-P, and P-N bonds in the current work present the candidacy of bismuth as a versatile photocatalyst for small molecule activation.

Pyrazolidinone-Aided Ru(II)-Catalyzed Regioselective C-H Annulation with Allenes.

Regioselective annulation of allenes via C-H activation represents an elegant synthetic approach toward the construction of valuable scaffolds. Considering the importance of allenes, herein we developed an unprecedented Ru(II)-catalyzed highly regioselective redox-neutral C-H activation/(4 + 1)-annulation of 1-arylpyrazolidinones employing allenyl acetates to access pyrazolo[1,2-a]indazol-1-one derivatives. Additionally, allenyl cyclic carbonates, which were never tested in C-H activation, were utilized to construct a similar class of heterocycles having a pendent alcohol functionality. Notably, double C-H functionalization was achieved by a simple modification of reaction conditions. The synthetic significance of this methodology is underscored by late-stage modification of natural products, broad substrate scope, gram-scale synthesis, and postfunctionalizations.

Rh(iii)-catalyzed sp3/sp2-C-H heteroarylations via cascade C-H activation and cyclization.

The development of an efficient strategy for facile access to quinoline-based bis-heterocycles holds paramount importance in medicinal chemistry. Herein, we describe a unified approach for accessing 8-(indol-3-yl)methyl-quinolines by integrating Cp*Rh(iii)-catalyzed C(sp3)-H bond activation of 8-methylquinolines followed by nucleophilic cyclization with o-ethynylaniline derivatives. Remarkably, methoxybiaryl ynones under similar catalytic conditions delivered quinoline tethered spiro[5.5]enone scaffolds via a dearomative 6-endo-dig C-cyclization. Moreover, leveraging this method for C8(sp2)-H bond activation of quinoline-N-oxide furnished biologically relevant oxindolyl-quinolines. This reaction proceeds via C(sp2)-H bond activation, regioselective alkyne insertion, oxygen-atom-transfer (OAT) and intramolecular nucleophilic cyclization in a cascade manner. One C-C, one C-N and one C[double bond, length as m-dash]O bond were created with concomitant formation of a quaternary center.

A highly diastereoselective one-pot Ugi/radical spirocyclization/aza-Michael addition sequence.

We hereby report a highly diastereoselective synthesis of chalcogenated azaspirotricycles via a one-pot Ugi/spirocyclization/aza-Michael addition sequence. The reaction proceeds via a key visible light mediated spirocyclization step under mild, metal-free and energy efficient conditions. A variety of complex sulfenylated and selenylated azaspirotricycles were obtained in good yields. The reaction was found to be scalable and preliminary mechanistic studies indicated that the spirocyclization step proceeds via radical intermediates.

Rh(II)-Catalyzed Denitrogenative Reaction of N-Sulfonyl-1,2,3-triazoles with Quinolones and Isoquinolones.

Herein, we developed an efficient approach to access biologically relevant 2-aminoquinolines and 1-aminoisoquinolines from readily available N-sulfonyl-1,2,3-triazoles and 2-quinolones or 1-isoquinolones. This transformation involves the selective O-H insertion of these derivatives onto the in situ generated Rh-azavinyl carbenes (Rh-AVC) followed by rearrangement. The reaction proceeds smoothly under operationally simple conditions and the protocol was found to be scalable.

Access to Polysubstituted Furan Derivatives via Cascade Oxy-palladation and Hydrocarbofunctionalization of Unactivated Alkenes.

The development of an expedient strategy for the synthesis of biologically relevant multisubstituted furans is a much-desired yet challenging task. Herein, we report an efficient and versatile strategy involving two different pathways for the construction of diverse polysubstituted C3- and C2-substituted γ-furanyl carboxylic acid derivatives. The synthetic approach for C3-substituted furans involves intramolecular cascade oxy-palladation of alkyne-diols followed by the regioselective coordinative insertion of unactivated alkenes. In contrast, C2-substituted furans were obtained exclusively by performing the protocol in a tandem manner.

A visible light mediated alkyl sulfonylative cascade using Hantzsch esters via SO2 insertion.

We hereby report a visible light mediated alkyl sulfonylative cascade cyclization of alkynyl and dialkynyl cyclohexadienones via SO2 insertion. The protocol utilizes alkyl Hantzsch esters as the alkyl source and DABSO as the SO2 source with 4-CzIPN as the organophotocatalyst. A variety of dihydrochromenone derivatives were obtained in good yields under mild energy efficient conditions. Additionally, fluorescence quenching and control studies were carried out to probe the mechanism.

Diphenyl Ditelluride: An Unconventional Reducing Agent in the Sulfonylative Cascade of Alkynyl Cyclohexadienones.

Herein, we report a reductive hydrazo-sulfonylative difunctionalization cascade of alkynyl cyclohexadienones employing PhTeTePh as an uncommon reducing agent. Diphenyl ditelluride is a commercially available solid with a good solubility profile in most organic solvents, and this is the first report illustrating it as a reducing agent. The protocol afforded a variety of difunctionalized dihydrochromenones and dihydrobenzofuranones in good yields under relatively mild conditions. The reactions were scalable, and mechanistic studies were conducted to probe the reaction mechanism. Additionally, photophysical studies of the products were carried out, which revealed that they had significant absorption (400-450 nm) and emission (520-570 nm) in the visible region.

Pd(ii)-catalyzed ß- and γ-C-(sp3)-H dienylation with allenyl acetates.

Recent years have seen the emergence of transition metal catalyzed C-H activation as a powerful synthetic tool in organic chemistry. Allenes have fascinated synthetic chemists due to their unique reactivity. While directing group assisted functionalization of C(sp2)-H bonds with allenes is well documented in the literature, their coupling with more challenging aliphatic C(sp3)-H bonds remains elusive. In this regard, we hereby report a Pd(ii) catalyzed 8-aminoquinoline directed aliphatic C(sp3)-H dienylation protocol using allenyl acetates. A variety of carboxylic acids including fatty acids and amino acids were efficiently functionalized at ß and γ-positions to afford diversely functionalized 1,3-dienes. Preliminary mechanistic studies revealed the crucial role of the base in the success of the transformation. The reaction proceeds via regioselective 2,3-migratory insertion of the allene with the alkylpalladium(ii) species followed by ß-acetoxy elimination.

Ru(II)-Catalyzed [4 + 2]-Annulation and Arylation of 1,4-Naphthoquinones.

Naphthoquinones form the core of a variety of drugs and natural products. As a result, the conjugation of 1,4-naphthoquinones with organic building blocks would offer a facile strategy toward scaffolds of biological interest. In this regard, we hereby report a Ru(II)-catalyzed [4 + 2] annulation of 1,4-naphthoquinones with benzoic acids to afford various naphthoquinone lactones. Additionally, ketone directed arylation of naphthoquinones using acetophenones under Ru(II)-catalysis was also illustrated. The feedstock availability of these precursors allowed access to a large library of naphthoquinone derivatives in good to excellent yields under fairly mild conditions. The practicality of these protocols was justified by carrying out a gram scale synthesis and further functionalizations. Also, preliminary mechanistic studies were carried out to probe the reaction mechanism.

α-Carbonyl sulfoxonium ylides in transition metal-catalyzed C-H activation: a safe carbene precursor and a weak directing group.

Transition metal-catalyzed cross-coupling of sp2 C-H bonds with diazo compounds via carbene migratory insertion represents an efficient strategy for the construction of C-C and C-heteroatom bonds in organic synthesis. Despite the popularity of diazo compounds as coupling partners in C-H activation, they pose serious safety and stability issues due to potential exothermic reactions linked with the release of N2 gas. However, compared with diazo compounds, sulfoxonium ylides are generally crystalline solids, more stable, widely used in industrial scales, and easier/safer to prepare. Therefore, recent years have witnessed an upsurge in employing α-carbonyl sulfoxonium ylides as an alternative carbene surrogate in transition metal-catalyzed C-H activation. Unlike diazo compounds, α-carbonyl sulfoxonium ylides contain inherent potential to serve as a coupling partner as well as a weak directing group. This review will summarize the progress made in both categories of reactions.

Ru(II)-Catalyzed Regioselective Annulation of 2-Hydroxystyrenes with Allenyl Acetates via Vinylic C-H Activation.

Herein, we disclose an unprecedented and robust Ru(II)-catalyzed non-oxidative [5+1] annulation of 2-hydroxystyrenes with allenyl acetates to access biologically relevant chromene skeletons. The heteroatom on allene plays a pivotal role in controlling the regioselectivity of migratory insertion, and the reaction proceeds through a Ru-σ-allyl pathway, which has been elusive so far in C-H activation reactions with allenes. The protocol is sustainable in nature as it proceeds at room temperature and avoids the use of any toxic metal oxidants. In addition, the synthetic utility of the protocol was also demonstrated by late stage functionalization and modular synthesis of various natural product conjugates.

Substrate-Dependent Denitrogenative Rearrangements of Rhodium Azavinyl Carbenes Involving 1,2-Aryl Migration.

Herein, we disclose substrate-dependent rearrangements of 4-substituted N-sulfonyl-1,2,3-triazoles under Rh(II)-catalysis via denitrogenation. The reaction pathways included key 1,2-aryl migration via the formation of intermediatory phenonium ion, which is elusive so far with Rh-azavinyl carbenes. Intriguingly, the transformations were completely dependent on the substituent present leading to different scaffolds like enaminones, pyrrol-3-ones, and azadienes. Hammett studies provided essential insights into the carbocationic intermediate formation. The developed methodology featured simple reaction conditions, excellent functional group compatibility, and broad substrate scope.

Regioselective Dichotomy in Ru(II)-Catalyzed C-H Annulation of Aryl Pyrazolidinones with 1,3-Diynes.

Herein, we present a substrate-controlled regiodivergent strategy for the selective synthesis of C3 or C2-alkynylated indoles via ruthenium-catalyzed [3 + 2]-annulation of readily available pyrazolidinones and 1,3-diynes. Remarkably, C3-alkynylated indoles were obtained in good yields when 1,4-diarylbuta-1,3-diynes were employed as the coupling partners. On the other hand, dialkyl-1,3-diynes led to the selective formation of C2-alkynylated indoles. The key features of the strategy are the operationally simple conditions and external-oxidant-free, broad-scope, and substrate-switchable indole synthesis. Scale-up reactions and further transformations expanded the synthetic utility of the protocol.

Dual Photoredox Cobalt Catalyzed [4+1] Annulation and C-H Alkoxylation.

Herein, we developed two distinct pyridine N-oxide directed C-H activation protocols to achieve [4+1] annulation and alkoxylation of benzamide derivatives by merging Co-catalysis with visible-light photoredox catalysis. The protocols deliver the respective products in good yields under facile conditions at room temperature. The use of an inexpensive photocatalyst coupled with molecular oxygen bypassing the need of stoichiometric oxidants forms the chief highlight of the work. The protocols are scalable and the products could be further modified. Additionally, preliminary studies were carried out to probe the reaction mechanism.

A metal-free four-component sulfonylation, Giese cyclization, selenylation cascade via insertion of sulfur dioxide.

We hereby report a highly regio- and diastereoselective arylsulfonylation-radical cyclization-selenylation cascade of alkynyl cyclohexadienones for the facile synthesis of highly functionalized dihydrochromenones. The protocol utilizes aryldiazonium salts as aryl partners and DABSO as a benign SO2 source and also as a redox mediator. Additionally, we also developed a visible light mediated protocol wherein diaryliodonium salts were used as the aryl partners at room temperature.

Visible-Light Mediated Arbuzov-Like Reaction with Thiophenols.

We hereby disclose, a visible light mediated addition of sulfenyl radicals to trialkyl phosphites to access functionalized phosphorothioates. The use of cheap and readily available Eosin Y as a photocatalyst under mild energy efficient conditions bypassing the use of external oxidants forms the chief highlight of the work. The protocol is scalable and mechanistic studies indicate that the reaction proceeds through an ionic-Arbuzov like pathway from phosphoranyl radicals.

Pd(II)-Catalyzed Transient Directing Group-Assisted Regioselective Diverse C4-H Functionalizations of Indoles.

The development of a rational strategy for achieving site-selective C4-H halogenation of indoles is an appealing yet challenging task. Herein, we disclose a Pd(II)-catalyzed transient directing group (TDG)-assisted methodology for realizing C4 chlorination/bromination of indoles employing glycine as the TDG and NFSI as a bystanding oxidant. The use of inexpensive and commercially available CuX2 as the halide source is the key highlight of this protocol. Furthermore, the TDG methodology was also extended to accessing C4 acetoxylated indoles employing acetic acid as the acetate source and 1-fluoro-2,4,6-trimethylpyridinium triflate as the oxidant.

Rh(iii)-Catalyzed [5 + 1] annulation of 2-alkenylanilides and 2-alkenylphenols with allenyl acetates.

Herein, we report a mild and highly regioselective Rh(iii)-catalyzed non-oxidative [5 + 1] vinylic C-H annulation of 2-alkenylanilides with allenyl acetates, which has been elusive so far. The reaction proceeds via vinylic C-H activation, regioselective 2,3-migratory insertion, ß-oxy elimination followed by nucleophilic cyclization to get direct access to 1,2-dihydroquinoline derivatives. The strategy was also successfully extended to C-H activation of 2-alkenylphenols for constructing chromene derivatives. In the overall [5 + 1] annulation, the allene serves as a one carbon unit. The acetate group on the allene is found to be crucial both for controlling the regio- and chemoselectivity of the reaction and also for facilitating ß-oxy elimination. The methodology was scalable and also further extended towards late stage functionalization of various natural products.

Cobalt-catalyzed highly diastereoselective [3 + 2] carboannulation reactions: facile access to substituted indane derivatives.

Efficient oxidative [3 + 2] annulation reaction involving aryl hydrazones and heterobicyclic alkenes has been realized with inexpensive and earth-abundant cobalt salts under aerobic conditions. The reaction proceeds via directing-group-assisted C-H activation and exo-selective migratory insertion, followed by the intramolecular nucleophilic attack of the alkylcobalt(III) species onto the imine with high anti-diastereoselectivity to provide complex indane derivatives. The generation of three contiguous stereogenic centers within the indanyl unit and the avoidance of the use of stoichiometric amounts of metal oxidants make this transformation more valuable and appealing.