Sustainable Synthesis through Catalyst-Free Photoinduced Cascaded Bond Formation.

The beginning of photochemical reactions revolutionized synthetic chemistry through sustainable practices. This review explores cutting-edge developments in leveraging light-induced processes for generating cascaded C-C and C-hetero bonds without catalysts. Significantly, catalyst-free photoinduced methodologies have garnered considerable attention, especially in the creation of varied heterocyclic frameworks for drug design and the synthesis of natural products. The article delves into underlying mechanisms, addresses limitations, and evaluates various methodologies, emphasizing the potential of photocatalyst and transition metal-free photochemical reactions to enhance sustainability. Divided into two sections, it covers recent strides in C-C and C-heteroatom and multiple C-heteroatom bond formation reactions.

Moisture-resistant radical anions of quinoxalin-2(1H)-ones in aerial dioxygen activation.

This study demonstrates the successful formation of a radical anion intermediate in a moist atmosphere, facilitating chemical reactions by activating aerial dioxygen through a single electron transfer (SET) mechanism. Derived from deprotonating quinoxaline-2(1H)-one with KOtBu, it shows potential in oxygenation chemistry. Validation comes from radical scavenging and EPR experiments.

Mimicking Ozonolysis via Mechanochemistry: Internal Alkynes to 1,2-Diketones using H5IO6.

Utilizing periodic acid as an environmentally benign oxidizing agent, this study introduces a novel mechanochemical method that mimics ozonolysis to convert internal alkynes into 1,2-diketones, showcasing effective emulation of ozone's reactivity. Notably, this oxidation occurs at room temperature in aerobic conditions, eliminating the need for toxic transition metals, hazardous oxidants, or expensive solvents. Through control experiments validating the mechanism, substantial evidence supports a concerted reaction pathway. This progress marks a significant stride toward cleaner and more efficient chemical synthesis, mitigating the environmental impact of conventional processes. Assessing the green chemistry metrics in both solvent-free and previously reported solvent-based methods, our eco-friendly protocol demonstrates an E-factor of 7.40, a 51.7 % atom economy, a 45.5 % atom efficiency, 100 % carbon efficiency, and 11.9 % reaction mass efficiency when solvents are not used.

Atom Transfer Radical Addition Reactions of Quinoxalin-2(1H)-ones with CBr4 and Styrenes Using Mes-Acr-MeClO4 Photocatalyst.

The atom transfer radical addition (ATRA) reaction is defined as a method for introducing halogenated compounds into alkenes via a radical mechanism. In this study, we present an ATRA approach for achieving regioselective functionalization of quinoxalin-2(1H)-ones by activating C-Br bonds of CBr4 and subsequent trihaloalkyl-carbofunctionalization of styrenes employing the 9-mesityl-10-methylacridinium perchlorate (Fukuzumi) photocatalyst under 3W blue LED (450-470 nm) irradiation. This three-component radical cascade process demonstrates remarkable efficiency in the synthesis of 1-methyl-3-(3,3,3-tribromo-1-(4-chlorophenyl)propyl)quinoxalin-2(1H)-one derivatives.

Photocatalyst- and Transition Metal-Free Light-Induced Borylation Reactions.

The increasing global warming concerns have propelled a surge in the demand for sustainable energy sources within the domain of synthetic organic chemistry. A particularly prominent area of research has been the development of mild synthetic strategies for generating heterocyclic compounds. Heterocyclic compounds containing boron have notably risen to prominence as pivotal reagents in a myriad of organic transformations, showcasing their wide-ranging applicability. This comprehensive review is aimed at collecting the literature pertaining to borylation reactions induced by light, specifically focusing on photocatalyst-free and transition metal-free methodologies. The central emphasis is on delving into selective mechanistic investigations. The amalgamation and analysis of these research insights elucidate the substantial potential inherent in eco-friendly approaches for synthesizing heterocyclic compounds, thus propelling the landscape of sustainable organic chemistry.

Investigation of the Effect of Solvents on the Synthesis of Aza-flavanone from Aminochalcone Facilitated by Halogen Bonding.

It has been recognized that CBr4 can give rise to a noncovalent interaction known as halogen bond (XB). CBr4 was found to catalyze, in terms of XB formation, the transformation of 2'-aminochalcone to aza-flavanone through an intramolecular Michael addition reaction. The impact of XB and the resulting yield of aza-flavanone exhibited a pronounced dependence on the characteristics of the solvent. Notably, yields of 88% in ethanol and 33% in DMSO were achieved, while merely a trace amount of the product was detected in benzene. In this work, we use a computational modeling study to understand this variance in yield. The reaction is modeled at the level of density functional theory (based on the M06-2X exchange-correlation functional) with all-electron basis sets of triple-ζ quality. Grimme's dispersion correction is incorporated to account for the noncovalent interactions accurately. Harmonic frequency calculations are carried out to establish the character of the optimized structures (minimum or saddle point). Our calculations confirm the formation of an XB between CBr4 and the reacting species and its role in lowering the activation energy barrier. Stronger orbital interactions and significant lowering of the steric repulsion were found to be important in lowering the activation barrier. The negligible yield in the nonpolar solvent benzene may be attributed to the high activation energy as well as the inadequate stabilization of the zwitterionic intermediate. In ethanol, a protic solvent, additional H-bonding contributes to further lowering of the activation barrier and better stabilization of the zwitterionic intermediate. The combined effects of solvent polarity, XB, and H-bond are likely to give rise to an excellent yield of aza-flavanone in ethanol.

Stereoselective Synthesis of Z-Styryl Sulfides from Nucleophilic Addition of Arylacetylenes and Benzyl Thiols.

The stereoselective synthesis of Z-anti-Markovnikov styryl sulfides via an anionic thiolate-alkyne addition reaction was achieved when the terminal alkynes and benzyl mercaptans were reacted using tBuOLi (0.5 equiv) in EtOH under ambient conditions. Exclusive stereoselectivity (ca. 100%) was achieved by stereoelectronic control via anti-periplanar and anti-Markovnikov addition of benzylthiolates to phenylacetylenes. Solvolysis of lithium thiolate ion pairs in ethanol significantly suppresses the competing formation of the E-isomer. A remarkable enhancement of the Z-selectivity under a longer reaction time was observed.

Chemodivergent Chalcogenation of Aryl Alkynoates or N-Arylpropynamides Using 9-Mesityl-10-Methylacridinium Perchlorate Photocatalyst.

Herein we report a cascaded chalcogenation of aryl alkynoates or N-arylpropynamides using 9-mesityl-10-methylacridinium perchlorate as a visible light photocatalyst to obtain selectively either 3-sulfenylated/selenylated coumarins or spiro[4,5]trienones. In a radical initiated process, the spiro-cyclization reaction was favored due to the presence of a -OMe or -F substituent at the para position of the aryl group, which helped to stabilize the allylic radical intermediate formed during the reaction. Otherwise, 6-endo-trig cyclization led to 3-sulfenylated/selenylated coumarins. Overall, the new C-S/C-Se, C-C, and C═O bonds were formed in a single step. The Stern-Volmer quenching study, EPR experiments, light ON-OFF experiments, radical trapping experiments, etc., helped to understand the radical-based mechanism.

CsPbBr3 Perovskite Photocatalyst in Chemodivergent Functionalization of N-Methylalkanamides Using CBr4.

Herein we have developed a strategy for chemodivergent functionalization of N-methylalkanamides via C-Br bond activation of CBr4, using an orthorhombic CsPbBr3 perovskite photocatalyst under blue LEDs (450-470 nm). The selectivity of whether a 5-exo-trig spiro cyclization or a 6-endo-trig cyclization occurred depended on the stability of the radical intermediate that was formed after the addition of the bromide radical to the starting compound to obtain 3,8-dibromo-1-methyl-4-phenyl-1-azaspiro[4.5]deca-3,6,9-trien-2-on or 3-bromo-1-methyl-4-phenyl-1-azaspiro[4.5]deca-3,6,9-triene-2,8-dione or 3-bromo-6-(tert-butyl)-1-methyl-4-phenylquinolin-2(1H)-one.

Regioselective synthesis of phenanthridine-fused quinazolinones using a 9-mesityl-10-methylacridinium perchlorate photocatalyst.

Herein, we demonstrate a regioselective intramolecular C-N cross-coupling for the synthesis of 14H-quinazolino[3,2-f]phenanthridin-14-one by using 9-mesityl-10-methylacridinium perchlorate as the visible-light (450-470 nm) photocatalyst. The experiments with BHT, TEMPO, and Stern-Volmer quenching studies helped to rationalize a radical pathway via a SET mechanism.

Activation of C-Br Bond of CBr4 and CBrCl3 Using 9-Mesityl-10-methylacridinium Perchlorate Photocatalyst.

Herein, we report the activation of the C-Br bond of CBrX3 (X = Cl, Br) using 9-mesityl-10-methylacridinium perchlorate as a visible-light (12W blue LED, 450-455 nm) photocatalyst for the synthesis of gem-dihaloenones from terminal alkynes. An electron transfer from CBrX3 to Mes-Acr-MeClO4 led to the formation of •+CBrX3 which subsequently resulted in the intermediate +CX3. Next, C-C cross-coupling of +CX3 with terminal alkynes was the key path to obtain the gem-dihaloenones. Radical trapping experiments with TEMPO, BHT, and Stern-Volmer quenching studies helped to understand that the reaction proceeded via the SET mechanism.

Visible-Light Promoted Regioselective Oxygenation of Quinoxalin-2(1H)-ones Using O2 as an Oxidant.

A visible-light-mediated sustainable approach for metal-free oxygenation of quinoxalin-2(1H)-one by employing Mes-Acr-MeClO4 as a photocatalyst without using any additive or cocatalyst is reported here. O2 served as the eco-friendly and green oxidant source for this conversion. In addition, the protocol exhibited high regioselectivity and tolerance toward a broad spectrum of functional groups to furnish quinoxaline-2,3-diones in good to excellent yields.

CBr4 catalyzed activation of α,ß-unsaturated ketones.

We have shown here that weak interactions such as halogen bonding (XB) can be used to activate the carbonyl group of α,ß-unsaturated ketones. Carbon tetrabromide (CBr4) has been used as the sole reagent for the selective synthesis of flavanones and aza-flavanones from the corresponding 2'-hydroxy- and 2'-aminochalcones under metal-free and additive-free conditions. DFT calculations support the catalytic role of XB between the oxygen of chalcones and CBr4 in these reactions.

DDQ in mechanochemical C-N coupling reactions.

2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) is a commonly known oxidant. Herein, we report that DDQ can be used to synthesize 1,2-disubstituted benzimidazoles and quinazolin-4(3H)-ones via the intra- and intermolecular C-N coupling reaction under solvent-free mechanochemical (ball milling) conditions. In the presence of DDQ, the intramolecular C(sp2)-H amidation of N-(2-(arylideneamino)phenyl)-p-toluenesulfonamides leads to 1,2-disubstituted benzimidazoles and the one-pot coupling of 2-aminobenzamides with aryl/alkyl aldehydes resulted in substituted quinazolin-4(3H)-one derivatives in high yields.

3-Arylsulfonylquinolines from N-Propargylamines via Cascaded Oxidative Sulfonylation Using DABSO.

We report a cascaded oxidative sulfonylation of N-propargylamine via a three-component coupling reaction using DABCO·(SO2)2 (DABSO). 3-Arylsulfonylquinolines were obtained by mixing diazonium tetrafluoroborate, N-propargylamine, and DABSO under argon atmosphere in dichloroethane (DCE) for 1 h. In a radical pathway, DABSO was utilized as the sulfone source and an oxidant in this radical-mediated cascaded reaction.

Regiodivergent C-N Coupling of Quinazolinones Controlled by the Dipole Moments of Tautomers.

Herein, we report that the dipole moments of tautomers can be the controlling factor for regiodivergent synthesis of either 14H-quinazolino[3,2-f]phenanthridin-14-ones or 6H-quinazolino[1,2-f]phenanthridin-6-ones, selectively, from unmasked 2-([1,1'-biphenyl]-2-yl)quinazolin-4(3H)-one. An intramolecular C(sp2)-NH coupling reaction mediated by PhI(OCOOCF3)2 could lead to two different regioisomers selectively at different temperatures when the dielectric constants of solvents like hexafluoroisopropanol and trifluoroacetic acid matched with the tautomer's dipole moments.

t BuOLi-promoted terminal alkyne functionalizations by aliphatic thiols and alcohols.

Selective radical addition to terminal alkynes is always a difficult task to achieve because it gives a mixture of stereo- and regioisomers. Herein we describe the selective addition of aliphatic thiols or alcohols to N-phenylpropiolamides (terminal alkynes) using lithium tert-butoxide (tBuOLi) in ethanol as a promoter. Mechanistically, it has been shown that the reaction proceeded through the generation of a thiyl radical intermediate, and the amide group in N-phenylpropiolamide could help in the activation of the alkyne, which led to thioacetalization via the formation of a (Z)-selective anti-Markovnikov vinyl sulfide. The (Z)-selectivity during the formation of vinyl sulfides was controlled by an intramolecular sulfur⋯oxygen interaction.

Reported Catalytic Hydrofunctionalizations that Proceed in the Absence of Catalysts: The Importance of Control Experiments.

The enlarged landscape of catalysis lies in the heart of chemistry. As the journey has set a milestone in organic synthesis, its darker side has not entered into the limelight. Studies disclose that the reported reactions by using catalysts were also attainable in the absence of catalysts in many cases. This article presents a literature collection that includes the significance of control experiments in hydrofunctionalization reactions. Systematic analysis reveals that the catalysts are ambiguous and might be unessential in chemical reactions enlisted here.

Chlorinative Cyclization of Aryl Alkynoates Using NCS and 9-Mesityl-10-methylacridinium Perchlorate Photocatalyst.

In a chlorinative cyclization, Mes-Acr-MeClO4 acted as a visible-light photocatalyst to obtain 3-chlorocoumarins from aryl alkynoates and N-chlorosuccinimide (NCS). The radical initiated reaction proceeded in a cascading manner via Cl- addition to alkynoates. Next, 5-exo-trig spirocyclization and subsequent 1,2-ester migration led to the formation of C-C and C-Cl bonds.

Disulfide metathesis via sulfur⋯iodine interaction and photoswitchability.

The idea of constitutional dynamic chemistry (CDC) and dynamic combinatorial chemistry (DCC) is widespread in the literature using the chemistry of disulfides. The synthesis of unsymmetrical diaryl disulfides is challenging due to the presence of a weak S-S bond. We report herein the synthesis of unsymmetrical diaryl disulfides from two symmetrical disulfides via a cross-metathesis reaction which was controlled by a weak sulfur⋯iodine (S⋯I) interaction. The unsymmetrical disulfides were stable in acetonitrile solution in the presence of N-iodosuccinimide (NIS), and found to be reversibly photoswitchable to the symmetrical disulfides under visible light irradiation.