Unified Approach to Diverse Heterocyclic Synthesis: Organo-Photocatalyzed Carboacylation of Alkenes and Alkynes from Feedstock Aldehydes and Alcohols.

We report an organo-photocatalyzed carboacylation reaction that offers a springboard to create chemical complexity in a diversity-driven approach. The modular one-pot method uses feedstock aldehydes and alcohols as acyl surrogates and commercially available Eosin Y as the photoredox catalyst, making it simple and affordable to introduce structural diversity. Several biologically relevant skeletons have been easily synthesized under mild conditions in the presence of visible light irradiation by fostering a radical acylation/cyclization cascade. The proposed reaction mechanism was further illuminated by a number of spectroscopic studies. Furthermore, we applied this protocol for the late-stage functionalization of pharmaceuticals and blockbuster drugs.

Transforming Non-innocent Phenalenyl to a Potent Photoreductant: Captivating Reductive Functionalization of Aryl Halides through Visible-Light-Induced Electron Transfer Processes.

Herein, we have established a phenalenyl-based molecular scaffold which serves as a potent photoreductant utilizing the empty NBMO in the presence of a base to form a radical anion which, upon photoexcitation, behaves as a stronger reductant and accomplishes the cleavage of strong C-X (X = Cl, Br, I) bonds under milder reaction conditions. The base was found to be involved in a dual role of electron and hydrogen atom donor. Further, the aryl radical formed by the homolysis of C-X bonds in this technique was captured for the Csp2-Csp2 coupling with unactivated arenes. The photoreductant potency of the phenalenyl-based catalytic system was further extended to C-P as well as C-B bond formation reactions. EPR and lifetime studies reveal the formation of a persistent radical having a sufficient lifetime to take part in the reaction by the PET mechanism. Different spectroscopic techniques combined with DFT calculations were utilized for the characterization of active catalytic species and for the elucidation of plausible mechanistic pathways. This not only is the initial report of the application of phenalenyl as a photoreductant but also provides a completely metal-free (alkali and transition metal) approach for the challenging reductive functionalization of aryl halides at room temperature.

Electrochemical Activation of the C-X Bond on Demand: Access to the Atom Economic Group Transfer Reaction Triggered by Noncovalent Interaction.

An atom economic method demonstrates the involvement of noncovalent interaction via hydrogen or halogen bonding interaction in triggering paired electrolysis for the group transfer reactions. Specifically, this method demonstrated the bromination of several aromatic and heteroaromatic compounds through the activation of the C(sp3)-Br bond of organic-bromo derivatives on demand. This electrochemical protocol is mild, and mostly no additional electrolyte is needed, which makes the workup process straightforward. Unlike the existing regioselective monobromination methods, this work utilizes a relatively small amount (1.2 equiv) of bromine surrogates that releases bromine on demand under the electrochemical condition and after completion of the reaction generates acetophenone as a useful byproduct. Green metrics indicate this protocol has a very good atom efficiency with an E-factor of 26.86 kg of waste/1 kg of product. In addition to the scale-up process, this strategy could be extended to the transfer of chlorine and thioaryl units. An extensive mechanistic study is accomplished to validate the hypothesis of noncovalent interaction using computational, spectroscopic, and cyclic voltammetry studies. Finally, the applicability of this newly developed nonbonding interaction to trigger paired electrolysis was extended to the chemoselective debromination of several dihalo organic compounds.

Visible-Light-Mediated Cross Dehydrogenative Coupling of Thiols with Aldehydes: Metal-Free Synthesis of Thioesters at Room Temperature.

Thioesters play a crucial role in biological systems and serve as important building blocks for organic synthesis. Herein, Eosin Y and TBHP mediated photochemical cross dehydrogenative coupling (PCDC) between feedstock aldehydes and thiols has been described at room temperature to synthesize thioesters. This thioesterification protocol proceeds smoothly to give the desired products in good to excellent yields by the suitable PCDC of both alkyl/aryl- aldehydes with a variety of alkyl/aryl-thiols and generates water and tBuOH as green byproducts. This method is also found to be scalable with good efficiency. Mechanistic investigations reveal that under this photochemical condition, the formation of acyl radical can be achieved from aldehyde. This acyl radical was further intercepted with an intermediate disulfide, generated in situ via the dehydrogenation of thiol to give the desired thioester. Moreover, disulfides, which are relatively easier to handle, also provided good to excellent yields in the optimized reaction condition. This protocol was further extended toward the more challenging direct transformation of alcohols to thioesters.

Probing the versatility of metallo-electro hybrid catalysis: enabling access towards facile C-N bond formation.

The development of versatile and mild methodologies for C-N bond construction has always been a hot topic of interest in synthetic organic chemistry. In recent years, electrochemistry has emerged as a promising green and sustainable environmentally benign approach to carry out these transformations under mild conditions utilizing electrons as oxidizing/reducing agents. The current state-of-the-art in combining electrocatalysis with transition metal catalysis has gained significant attention. This hybrid synthetic methodology has increasingly become a common tool and offers many potential advantages compared to direct electrolysis. This review comprehensively highlights recent developments in the merging of transition metal catalysis in electro-organic synthesis for the facile construction of C-N bonds. In this review major emphasis is given to mechanistic investigations and their synthetic applications of this hybrid catalysis.

Catalytic π-π Interactions Triggered Photoinduced Synthesis of Biaryls.

A highly regioselective photocatalytic method to access a variety of biaryl motifs under metal-free conditions has been developed. The organophotocatalyst is involved in π-π stacking interactions with the alkyne species, which promotes this photocatalytic process with thiophene. Mechanistic studies have shed light on these interactions and the overall process. Along with a broad functional-group tolerance and excellent regioselectivity, this protocol has been utilized in the late-stage functionalization of pharmaceuticals and other natural products.

Light-Induced Activation of C-X Bond via Carbonate-Assisted Anion-π Interactions: Applications to C-P and C-B Bond Formation.

We have presented a carbonate anion assisted photochemical protocol for the C-X bond activation. Anion-π interactions have been leveraged to generate aryl radicals from easily accessible aryl halides that are further utilized in C-P and C-B bond formation reactions with excellent reactivity and broad functional group tolerance. Spectroscopic investigations and DFT studies were conducted for mechanistic insights. This inexpensive method alleviates the use of a photocatalyst and the need of preactivation of the substrate for the light-induced activation of C-X bonds.

Exploring Eosin Y as a bimodular catalyst: organophotoacid mediated Minisci-type acylation of N-heteroarenes.

Here we report Eosin Y as a bimodular catalyst for Minisci-type acylation reactions. The formation of organic exciplexes between photoexcited Eosin Y and N-heteroarenes was found to be a stabilizing factor for photoacid catalysis under optimized conditions. Spectroscopic investigations such as steady state fluorescence quenching and dynamic lifetime quenching experiments were employed to better understand the role of Eosin Y as both a photoredox catalyst and a photoacid. Feedstock aldehydes were employed as acyl radical precursors for engaging in C-C bond formation reactions with a variety of nitrogen containing heterocycles.