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1. Catalyst‐Free Decarbonylative Trifluoromethylthiolation Enabled by Electron Donor‐Acceptor Complex Photoactivation

   https://doi.org/10.1002/adsc.202100469  

   Lipp, Alexander; Badir, Shorouk_O; Dykstra, Ryan; Gutierrez, Osvaldo; Molander, Gary_A (July 2021, Advanced Synthesis & Catalysis)

   Abstract A catalyst‐ and additive‐free decarbonylative trifluoromethylthiolation of aldehyde feedstocks has been developed. This operationally simple, scalable, and open‐to‐air transformation is driven by the selective photoexcitation of electron donor‐acceptor (EDA) complexes, stemming from the association of 1,4‐dihydropyridines (donor) withN‐(trifluoromethylthio)phthalimide (acceptor), to trigger intermolecular single‐electron transfer events under ambient‐ and visible light‐promoted conditions. Extension to other electron acceptors enables the synthesis of thiocyanates and thioesters, as well as the difunctionalization of [1.1.1]propellane. The mechanistic intricacies of this photochemical paradigm are elucidated through a combination of experimental efforts and high‐level quantum mechanical calculations [dispersion‐corrected (U)DFT, DLPNO‐CCSD(T), and TD‐DFT]. This comprehensive study highlights the necessity for EDA complexation for efficient alkyl radical generation. Computation of subsequent ground state pathways reveals that S_H2 addition of the alkyl radical to the intermediate radical EDA complex is extremely exergonic and results in a charge transfer event from the dihydropyridine donor to theN‐(trifluoromethylthio)phthalimide acceptor of the EDA complex. Experimental and computational results further suggest that product formation also occursviaS_H2 reaction of alkyl radicals with 1,2‐bis(trifluoromethyl)disulfane, generated in‐situ through combination of thiyl radicals. magnified image 

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2. Visible Light‐Assisted Direct C−H Acyloxylation of Polycyclic Aromatic Hydrocarbons using Carboxylic Acids

   https://doi.org/10.1002/adsc.202300043  

   K_Jha, Dhiraj; Sakkani, Nagaraju; Zhao, John_C‐G (May 2023, Advanced Synthesis & Catalysis)

   Abstract The direct C−H acyloxylation of polycyclic aromatic hydrocarbons (PAHs) with carboxylic acids as the acyloxylating agents was achieved via the electron‐donor‐acceptor (EDA) complexes between PAHs andN‐iodosuccinimide (NIS). This visible light‐assisted metal‐free C−H acyloxylation reaction provides an easy access to the desired aryl carboxylates from readily available PAHs and aliphatic and aromatic carboxylic acids under mild reaction conditions. magnified image 

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3. Photoredox-mediated hydroalkylation and hydroarylation of functionalized olefins for DNA-encoded library synthesis

   https://doi.org/10.1039/d1sc03191k  

   Badir, Shorouk O.; Lipp, Alexander; Krumb, Matthias; Cabrera-Afonso, María Jesús; Kammer, Lisa Marie; Wu, Victoria E.; Huang, Minxue; Csakai, Adam; Marcaurelle, Lisa A.; Molander, Gary A. (September 2021, Chemical Science)

   null (Ed.)

   DNA-encoded library (DEL) technology features a time- and cost-effective interrogation format for the discovery of therapeutic candidates in the pharmaceutical industry. To develop DEL platforms, the implementation of water-compatible transformations that facilitate the incorporation of multifunctional building blocks (BBs) with high C(sp 3 ) carbon counts is integral for success. In this report, a decarboxylative-based hydro alkylation of DNA-conjugated trifluoromethyl-substituted alkenes enabled by single-electron transfer (SET) and subsequent hydrogen atom termination through electron donor–acceptor (EDA) complex activation is detailed. In a further photoredox-catalyzed hydro arylation protocol, the coupling of functionalized, electronically unbiased olefins is achieved under air and within minutes of blue light irradiation through the intermediacy of reactive (hetero)aryl radical species with full retention of the DNA tag integrity. Notably, these processes operate under mild reaction conditions, furnishing complex structural scaffolds with a high density of pendant functional groups. 

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4. Challenges in the Highly Selective [3 + 1]-Cycloaddition of an Enoldiazoacetamide to Form a Donor–Acceptor Cis-Cyclobutenecarboxamide

   https://doi.org/10.3390/molecules26123520  

   Joyasawal, Sipak; Ma, Donghui; Doyle, Michael P. (June 2021, Molecules)

   A substituted donor–acceptor cyclobutenecarboxamide is synthesized with modest enantiocontrol through a chiral copper(I) complex catalyzed [3 + 1]-cycloaddition reaction of α-acyl diphenylsulfur ylides with 3-siloxy-2-diazo-3-butenamides. With a methyl substituent on the 4-position of the 3-butenamide, the cis-vicinal-3,4-disubstituted cyclobutenecarboxamide is formed with >20:1 diastereocontrol. Donor-acceptor 3-methyl-2-siloxycyclopropenecarboxamide is rapidly formed from the reactant enoldiazoamide and undergoes catalytic ring opening to give only the Z-γ-substituted metallo-enolcarbene. Elimination from 3-siloxy-2-diazo-3-pentenamide to form the conjugated 3-siloxy-2,4-pentadienamide is competitive but minimized at low temperature. 

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5. Solvation stabilizes intercarbonyl n→π* interactions and polyproline II helix

   https://doi.org/10.1039/D2CP00857B  

   Zondlo, Neal J. (June 2022, Physical Chemistry Chemical Physics)

   n→π* interactions between consecutive carbonyls stabilize the α-helix and polyproline II helix (PPII) conformations in proteins. n→π* interactions have been suggested to provide significant conformational biases to the disordered states of proteins. To understand the roles of solvation on the strength of n→π* interactions, computational investigations were conducted on a model n→π* interaction, the twisted-parallel-offset formaldehyde dimer, as a function of explicit solvation of the donor and acceptor carbonyls, using water and HF. In addition, the effects of urea, thiourea, guanidinium, and monovalent cations on n→π* interaction strength were examined. Solvation of the acceptor carbonyl significantly strengthens the n→π* interaction, while solvation of the donor carbonyl only modestly weakens the n→π* interaction. The n→π* interaction strength was maximized with two solvent molecules on the acceptor carbonyl. Urea stabilized the n→π* interaction via simultaneous engagement of both oxygen lone pairs on the acceptor carbonyl. Solvent effects were further investigated in the model peptides Ac-Pro-NMe 2 , Ac-Ala-NMe 2 , and Ac-Pro 2 -NMe 2 . Solvent effects in peptides were similar to those in the formaldehyde dimer, with solvation of the acceptor carbonyl increasing n→π* interaction strength and resulting in more compact conformations, in both the proline endo and exo ring puckers, as well as a reduction in the energy difference between these ring puckers. Carbonyl solvation leads to an energetic preference for PPII over both the α-helix and β/extended conformations, consistent with experimental data that protic solvents and protein denaturants both promote PPII. Solvation of the acceptor carbonyl weakens the intraresidue C5 hydrogen bond that stabilizes the β conformation. 

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