Generation of alkyl and acyl radicals by visible-light photoredox catalysis: direct activation of C-O bonds in organic transformations.

Alkyl and acyl radicals play a critical role in the advancement of chemical synthesis. The generation of acyl and alkyl radicals by activation of C-O bonds using visible-light photoredox catalysis offers a mild and environmentally benign approach to useful chemical transformations. Alcohols, carboxylic acids, anhydrides, xanthates, oxalates, N-phthalimides, and thiocarbonates are some examples of alkyl and acyl precursors that can produce reactive radicals by homolysis of the C-O bond. These radicals can then go through a variety of transformations that are beneficial for the construction of synthetic materials that are otherwise difficult to access. This study summarizes current developments in the use of organic photocatalysts, transition-metal photoredox catalysts, and metallaphotocatalysts to produce acyl and alkyl radicals driven by visible light.

Experimental and theoretical insights for designing Zn2+ complexes to trigger chemo-selective hetero-coupling of alcohols.

Designing well-defined Zn-complexes for sustainable dehydrogenative catalysis overcoming the difficulties associated with activating Zn2+(d10)-metal species is considered paramount goal in catalysis. Herein, we explore the plausibility of ß-alkylation of secondary alcohols with primary alcohols by well-defined 3d10 Zn-complexes. Detailed organometallic and catalytic investigations, in conjunction with computational analyses, were conducted to ascertain the potential involvement of the catalyst at various stages of the catalytic process.

Designing Cobalt(II) Complexes for Tandem Dehydrogenative Synthesis of Quinoline and Quinazoline Derivatives.

In this work, we have constructed three new Co(II) complexes in which steric features govern their structural geometry. The metal ligand-cooperation behavior of the alkoxy arm is utilized to explore the catalytic activities of these complexes with respect to dehydrogenation. A wide range of C-3-substituted quinoline and quinazoline derivatives were synthesized in high yields. The developed protocol's usefulness is enhanced by the chemoselective transformation of different fatty alcohols to synthesize heterocycles having distal unsaturation. Various kinetic, mechanistic, and control studies were conducted to comprehend the reaction route.

Manganese Complex Catalyzed Sequential Multi-component Reaction: Enroute to a Quinoline-Derived Azafluorenes.

The development of innovative synthetic strategies for constructing complex molecular structures is the heart of organic chemistry. This significance of novel reactions or reaction sequences would further enhance if they permitted the synthesis of new classes of structural motifs, which have not been previously created. The research on the synthesis of heterocyclic compounds is one of the most active topics in organic chemistry due to the widespread application of N-heterocycles in life and material science. The development of a new catalytic process that employs first-row transition metals to produce a range of heterocycles from renewable raw materials is considered highly sustainable approach. This would be more advantageous if done in an eco-friendly and atom-efficient manner. Herein we introduce, the synthesis of various new quinoline based azafluorenes via sequential dehydrogenative multicomponent reaction (MCR) followed by C(sp3)-H hydroxylation and annulation. Our newly developed, Mn-complexes have the ability to direct the reaction in order to achieve a high amount of desired functionalized heterocycles while minimizing the possibility of multiple side reactions. We also performed a series of control experiments, hydride trapping experiments, reaction kinetics, catalytic intermediate and DFT studies to comprehend the detailed reaction route and the catalyst's function in the MCR sequence.

Well-Defined Mn(II)-complex Catalyzed Switchable De(hydrogenative) Csp3 -H Functionalization of Methyl Heteroarenes: A Sustainable Approach for Diversification of Heterocyclic Motifs.

Catalytic activities of Mn(I) complexes derived from expensive MnBr(CO)5 salt have been explored in various dehydrogenative transformations. However, the reactivity and selectivity of inexpensive high spin Mn(II) complexes are uncommon. Herein, we have synthesized four new Mn(II) complexes and explored switchable alkenylation and alkylation of methyl heteroarenes employing a single Mn(II)catalyst. The developed protocol selectively furnishes a series of functionalized E-heteroarenes and C-alkylated heteroarenes with good to excellent yields. Various medicinally and synthetically useful compounds are successfully synthesized using our developed protocol. Various controls and kinetics experiments were executed to shed light on the mechaism,which reveals that α-C-H bond breaking of alcohol is the slowest step.

Ruthenium-catalyzed dehydrogenative cyclization to synthesize polysubstituted 4-quinolones under solvent-free conditions.

Herein, we describe acridine-based SNS-Ru pincer-catalysed unprecedented dehydrogenative annulation of alcohols with 2'-aminoacetophenone to synthesize 2,3-disubstituted-4-quinolones. The developed protocol was utilized with a wide range of alcohols with various aminoacetophenones. To expand the synthetic utility, 4-quinolones with antibiotic properties were synthesized and various important post-synthetic modifications of the synthesized scaffolds were performed. Various control experiments were performed to understand the mechanism, which showed that C-alkylation has the edge over N-alkylation and referred to the possibility of in situ alkenylation to branched ketones.

Progressive study on ruthenium catalysis for de(hydrogenative) alkylation and alkenylation using alcohols as a sustainable source.

At present, alcohols are considered sustainable starting materials that can be used in organic synthesis for various organic transformations and the preparation of commodity chemicals. Acceptorless dehydrogenation (AD) and borrowing hydrogen (BH) are two important methods for activating alcohols for alkenylation and alkylation. These approaches are sustainable because their process liberates water and in some cases (i.e., AD) molecular hydrogen as clean byproducts. Moreover, this area of research has attracted significant attention in the catalysis community, and various transition metals have been used to explore the same. Herein, in this review, we focus on the development of Ru-based catalyst systems for C-alkylation/alkenylation reactions via the AD or BH approach. This review also features a comparative study of the various Ru-catalysts used to optimize the reaction conditions. Furthermore, we extensively cover the outcomes of the mechanistic studies to describe the reaction pathways.

Change in the Product Selectivity in the Visible Light-Induced Selenium Radical-Mediated 1,4-Aryl Migration Process.

Herein, we demonstrate a visible light-induced selenium radical-mediated domino reaction of aryl alkynoates, for the synthesis of 1,1-diselenide alkene derivatives and selenium-containing α,ß-unsaturated carboxylic acid. The process is mild, metal free, easy to handle, and scalable. The decarboxylation step can be controlled by applying a catalytic amount of Eosin Y dye and cesium carbonate as a base. The methodology shows good functional group tolerance and provides decent yields of the products. In addition, the synthetic utility of this protocol was expanded further by preparing the allylic alcohol, α,ß-unsaturated ester, and vinylic halides.

Ru Doped Hydrotalcite Catalyzed Borrowing Hydrogen-Mediated N-Alkylation of Benzamides, Sulfonamides, and Dehydrogenative Synthesis of Quinazolinones.

An efficient Ru doped hydrotalcite catalyzed N-alkylation of benzamides and sulfonamides with alcohols via borrowing hydrogen catalysis is illustrated. Various primary alcohols, including benzyl, heteroaryl, and aliphatic alcohols, were alkylated in good to excellent yields. To shed light on the mechanistic details, several control studies and deuterium labeling experiments were performed. Mechanistic studies underpin that the reaction is going via a borrowing hydrogen pathway rather than an SN1 type mechanism. The reaction can be easily scaled up without any detrimental effect on the yield. The catalyst is also capable of synthesizing quinazolinone directly from 2-aminobenzamide and alcohols. Successful recyclability and high reactivity highlight the practical applicability of the catalyst.

Well-Defined NNS-Mn Complex Catalyzed Selective Synthesis of C-3 Alkylated Indoles and Bisindolylmethanes Using Alcohols.

Herein, we demonstrated Mn-catalyzed selective C-3 functionalization of indoles with alcohols. The developed catalyst can also furnish bis(indolyl)methanes from the same set of substrates under slightly modified reaction conditions. Mechanistic studies reveal that the C-3 functionalization of indoles is going via a borrowing hydrogen pathway. To highlight the practical utility, a diverse range of substrates including nine structurally important drug molecules are synthesized. Furthermore, we also introduced a one-pot cascade strategy for synthesizing C-3 functionalized indoles directly from 2-aminophenyl ethanol and alcohol.

Manganese catalyzed switchable C-alkylation/alkenylation of fluorenes and indene with alcohols.

The usage of earth-abundant, nontoxic transition metals in place of rare noble metals is a central goal in catalysis. This would be especially interesting when the reactivity and selectivity patterns can be tuned. Herein, we introduced the first Mn-catalyzed selective C-alkylation and olefination of fluorene, and indene with alcohols. Various substrates including benzylic, heteroaromatic, and aliphatic primary and secondary alcohols are employed as alkylating agents. Mechanistic investigations and a kinetic study underpin the involvement of the olefinated intermediate to furnish the alkylated product.

Ru-Catalyzed Selective Catalytic Methylation and Methylenation Reaction Employing Methanol as the C1 Source.

Methanol can be employed as a green and sustainable methylating agent to form C-C and C-N bonds via borrowing hydrogen (BH) methodology. Herein we explored the activity of the acridine-derived SNS-Ru pincer for the activation of methanol to apply it as a C1 building block in different reactions. Our catalytic system shows great success toward the ß-C(sp3)-methylation reaction of 2-phenylethanols to provide good to excellent yields of the methylated products. We investigated the mechanistic details, kinetic progress, and temperature-dependent product distribution, which revealed the slow and steady generation of in situ formed aldehyde, is the key factor to get the higher yield of the ß-methylated product. To establish the environmental benefit of this reaction, green chemistry metrics are calculated. Furthermore, dimerization of 2-naphthol via methylene linkage and formation of N-methylation of amine are also described in this study, which offers a wide range of substrate scope with a good to excellent yield.

Synthesis of 1,8-Dioxo-decahydroacridine Derivatives via Ru-Catalyzed Acceptorless Dehydrogenative Multicomponent Reaction.

A Ru-catalyzed acceptorless dehydrogenative multicomponent reaction has been developed. This reaction offers a cost-effective and simple operational strategy to synthesize biologically active 1,8-dioxodecahydroacridine derivatives. The protocol provides a wide range of substrate scope and various functional groups are also well tolerated under the reaction condition. To shed light on the mechanistic and kinetic study, some controlled experiments and deuterium labeling experiments were executed. A time-dependent product distribution experiment is also presented and the reaction scale-up is performed to highlight the practical utility of this strategy.

Acceptorless dehydrogenative construction of C[double bond, length as m-dash]N and C[double bond, length as m-dash]C bonds through catalytic aza-Wittig and Wittig reactions in the presence of an air-stable ruthenium pincer complex.

The construction of C[double bond, length as m-dash]N bonds was achieved by the dehydrogenative coupling of alcohol and azide via aza-Wittig type reaction. The reaction is catalyzed by an acridine-derived ruthenium pincer complex and does not use any oxidant. The present protocol offers a wide substrate scope, including aliphatic, aryl or heteroaryl alcohol/azides. This expeditious protocol was successfully applied to construct a C[double bond, length as m-dash]C bond directly from alcohol via dehydrogenative Wittig reaction. Furthermore, the synthesis of structurally important pyrrolo[1,4]benzodiazepine derivatives was also achieved by this methodology.

Sustainable Synthesis of Quinazoline and 2-Aminoquinoline via Dehydrogenative Coupling of 2-Aminobenzyl Alcohol and Nitrile Catalyzed by Phosphine-Free Manganese Pincer Complex.

A sustainable synthesis of quinazoline and 2-aminoquinoline via acceptorless dehydrogenative annulation is presented. The reaction is catalyzed by earth-abundant well-defined manganese complexes bearing NNS ligands. Furthermore, a one-pot synthetic strategy for the synthesis of 2-alkylaminoquinolines through sequential dehydrogenative annulation and N-alkylation reaction has also been demonstrated.

Phosphine free Mn-complex catalysed dehydrogenative C-C and C-heteroatom bond formation: a sustainable approach to synthesize quinoxaline, pyrazine, benzothiazole and quinoline derivatives.

Herein the first sustainable synthesis of quinoxalines, pyrazines and benzothiazoles catalysed by a phosphine free Mn(i) complex via acceptorless dehydrogenative coupling (ADC) is reported. This method is also applied successfully to synthesize quinolines via the dehydrogenation (removal of H2) and condensation (removal of H2O) reaction between 2-aminobenzyl alcohols and secondary alcohols.

Selective Synthesis of 2-Substituted and 1,2-Disubstituted Benzimidazoles Directly from Aromatic Diamines and Alcohols Catalyzed by Molecularly Defined Nonphosphine Manganese(I) Complex.

Herein, we present a selective synthesis of 2-substituted and 1,2-disubstituted benzimidazoles by acceptorless dehydrogenative coupling of aromatic diamine with primary alcohols. The reaction is catalyzed by a phosphine-free tridentate NNS ligand-derived manganese(I) complex.

Selective Hydrogenation of Nitriles to Primary Amines Catalyzed by a Cobalt Pincer Complex.

The catalytic hydrogenation of nitriles to primary amines represents an atom-efficient and environmentally benign reduction methodology in organic chemistry. This has been accomplished in recent years mainly with precious-metal-based catalysts, with a single exception. Here we report the first homogeneous Co-catalyzed hydrogenation of nitriles to primary amines. Several (hetero)aromatic, benzylic, and aliphatic nitriles undergo hydrogenation to the corresponding primary amines in good to excellent yields under the reaction conditions.

Cobalt-catalyzed hydrogenation of esters to alcohols: unexpected reactivity trend indicates ester enolate intermediacy.

The atom-efficient and environmentally benign catalytic hydrogenation of carboxylic acid esters to alcohols has been accomplished in recent years mainly with precious-metal-based catalysts, with few exceptions. Presented here is the first cobalt-catalyzed hydrogenation of esters to the corresponding alcohols. Unexpectedly, the evidence indicates the unprecedented involvement of ester enolate intermediates.

Direct catalytic olefination of alcohols with sulfones.

The synthesis of terminal, as well as internal, olefins was achieved by the one-step olefination of alcohols with sulfones catalyzed by a ruthenium pincer complex. Furthermore, performing the reaction with dimethyl sulfone under mild hydrogen pressure provides a direct route for the replacement of alcohol hydroxy groups by methyl groups in one step.