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Enantioenriched pyrrolidines and derivatives are ubiquitous substructures in compounds of importance to medicinal and biological chemistry. Herein, we report an efficient cobalt-catalyzed intramolecular asymmetric hydroamination reaction that produces chiral pyrrolidines with good to excellent yield and enantiocontrol. Compared with previously reported radical-involved methodologies for enantioenriched pyrrolidines, these conditions feature two elegant versatilities, enabling (1) the use of cobalt-catalyzed hydrogen atom transfer (HAT) to generate organocobalt intermediates that bring radical reaction to organometallic chemistry, and (2) enantioselective intramolecular C–N bond forging through an S N 2-like displacement involving dynamic kinetic resolution (DKR). This approach provides a new alternative and efficient methodology for enantioselective radical-involved C–N bond construction that can be used in the synthesis of both chiral pyrrolidines and homologous nitrogen heterocycles.

Nickel photocatalysis has recently become vital to organic synthesis, but how the Ni (II) X 2 L pre-catalyst (X = Cl, Br; L = bidentate ligand) becomes activated to Ni (I) XL has remained puzzling and is typically addressed on a case-by-case basis. Here, we reveal a general mechanism where light induces photolysis of the Ni (II) -X bond, either via direct excitation or triplet energy transfer. Photolysis produces Ni (I) XL and a halogen radical, X • . Subsequent hydrogen atom abstraction, often from the solvent, produces a C(sp 3 ) radical, R • , that recombines with Ni (I) to form organonickel(II) complexes, Ni (II) XRL. Rather than acting as a loss pathway, Ni (II) XRL behaves as a light-activated reservoir of Ni (I) via photolysis of the Ni (II) -C bond. These results explain the role of the solvent in protecting the catalyst from off-cycle dimerization, demonstrate that two photons are often required to drive the reaction, and show how tuning the ligand can control the concentration of active Ni (I) species. Nickel(II) dihalide precatalysts with bidentate nitrogen ligands are widely used in cross-coupling reactions, notably in combination with photosensitizers, forming catalytic systems that currently drive major conceptual and synthetic thrusts within organic chemistry. Here the authors show a general mechanism by which these precatalysts are converted to the reduced, catalytically active species, using a range of characterization and spectroscopic techniques.

The discovery of novel catalysis modes to generate a significant increase in structural complexity from readily available reactants is a fundamental goal in modern organic synthesis. Here, we report a photoinduced palladium-catalyzed hydrogen atom transfer triggered 1,2-difunctionalization of conjugated dienes. Without the employment of exogeneous photosensitizers and external oxidants, the cascade reaction realized the integration of remote functionalization of various C(sp 3 )-H bonds and selective difunctionalization of 1,3-dienes with 100% atom efficiency, allowing for the synthesis of structurally diverse amides with up to 90% yields. Given the prevalence of amides in pharmaceuticals and natural products, the current protocol has provided an efficient means to access highly functionalized amides from readily available carboxylic acid derivatives and 1,3-dienes.

Hirshfeld atom refinement (HAR) is generally the chosen method for obtaining accurate hydrogen atom parameters from X-ray diffraction data. Still, determination can prove challenging, especially in the case of atomic displacement parameters (ADPs). We demonstrate that such a situation can occur when the ADP values of the bonding partner of the hydrogen atom are not determined accurately. Atomic electron densities partially overlap and inaccuracies in the bonding neighbour ADPs can be partially compensated for with modifications to the hydrogen ADPs. We introduce a modified version of the original Hirshfeld partition: the exponential Hirshfeld partition, parameterized with an adjustable parameter ( n ) to allow control of the overlap level of the atomic electron densities which, for n = 1, is equivalent to the Hirshfeld partition. The accuracy of the HAR-like procedure using the new partition (expHAR) was tested on a set of organic structures using B3LYP and MP2 electron densities. Applying expHAR improved the hydrogen atom parameters in the majority of the structures (compared with HAR), especially in cases with the highest deviations from the reference neutron values. X —H bond lengths and hydrogen ADPs improved for 9/10 of the structures for B3LYP-based refinement and 8/9 for MP2-based refinement when the ADPs were compared with a newly introduced scale-independent similarity measure.

Nitrogenous compounds have been extensively utilized as hydrogen atom transfer (HAT) catalysts in photoredox reactions, with nitrogenous radical cations being the actual hydrogen atom abstractors. Building upon our previous work, 120 thermodynamic graphs of nitrogenous radical cations abstracting hydrogen atoms, which encompass seven vital thermodynamic parameters, are designed and established to elucidate their redox characteristics. Furthermore, the applications of thermodynamic graphs to select appropriate photocatalysts, assess the feasibility of the HAT process, and diagnose the possible activation mechanism were discussed, which would enable the utilities of nitrogenous compounds as HAT catalysts or nitrogenous radical cations as hydrogen atom abstractors in photoredox reactions.

A conceptually novel, trifunctional sulfoximine-mediated γ-functionalization of unactivated C(sp 3 )-H bonds has been achieved. The reaction is initiated by the photo-induced homolytic cleavage of an N-S bond in the absence of photosensitizer, and proceeds sequentially through a cascade of 1,5-hydrogen atom transfer, 1,4-functional group migration, desulfoximination and a Minisci reaction. A major feature of this approach is the use of sulfoximine as a traceless directing group. Other positive properties include mild conditions, simple operation, exclusive site-selectivity, high product diversity and the avoidance of additional photosensitizers. The protocol provides a new reaction mode for HAT-induced C(sp 3 )-H functionalization, and allows a much broader chemical space for sulfoximine studies.

N -Hydroxyphthalimide (NHPI) esters have emerged as powerful sources of alkyl radicals generated by single-electron transfer, but homolysis of NHPI ester to produce an alkyl radical and a phthalimide nitrogen radical is still in its infancy. In this study, we developed a light-induced method for generation of alkyl and phthalimide nitrogen radicals from NHPI esters and subsequent reactions of the radicals with [1.1.1]propellane and aryl aldehydes for rapid generation of bicycle [1.1.1]pentane ketones. This method does not require metals or photosensitizers, features a broad substrate scope (90 examples) and excellent functional group tolerance, and can be used for the functionalization of structurally complex natural products and drugs. Mechanistic investigations indicate that the reaction involves photoinduced homolytic cleavage of the Cs 2 CO 3 -NHPI ester complex to produce alkyl and phthalimide nitrogen radicals and subsequent hydrogen atom transfer between the phthalimide nitrogen radical and the aldehyde to generate an acyl radical.

Hirshfeld atom refinement (HAR) is a method which determines structural parameters from single-crystal X-ray diffraction data by using an aspherical atom partitioning of tailor-made ab initio quantum mechanical molecular electron densities without any further approximation. Here the original HAR method is extended by implementing an iterative procedure of successive cycles of electron density calculations, Hirshfeld atom scattering factor calculations and structural least-squares refinements, repeated until convergence. The importance of this iterative procedure is illustrated via the example of crystalline ammonia. The new HAR method is then applied to X-ray diffraction data of the dipeptide Gly–L-Ala measured at 12, 50, 100, 150, 220 and 295 K, using Hartree–Fock and BLYP density functional theory electron densities and three different basis sets. All positions and anisotropic displacement parameters (ADPs) are freely refined without constraints or restraints – even those for hydrogen atoms. The results are systematically compared with those from neutron diffraction experiments at the temperatures 12, 50, 150 and 295 K. Although non-hydrogen-atom ADPs differ by up to three combined standard uncertainties (csu's), all other structural parameters agree within less than 2 csu's. Using our best calculations (BLYP/cc-pVTZ, recommended for organic molecules), the accuracy of determining bond lengths involving hydrogen atoms from HAR is better than 0.009 Å for temperatures of 150 K or below; for hydrogen-atom ADPs it is better than 0.006 Å 2 as judged from the mean absolute X-ray minus neutron differences. These results are among the best ever obtained. Remarkably, the precision of determining bond lengths and ADPs for the hydrogen atoms from the HAR procedure is comparable with that from the neutron measurements – an outcome which is obtained with a routinely achievable resolution of the X-ray data of 0.65 Å.

The normalization of the polar functions Θ ℓ , m ( θ ) for the solution of Schrödinger’s equation for the Coulomb potential usually proceeds by appealing to the properties of Associated Legendre polynomials. We show how to achieve the normalization directly from the overall form of the solution and the recursion relation for its series part. When combined with a previous such normalization for the radial part of the solution, the entire hydrogen atom solution can be normalized without having to invoke any properties of special functions.

Avenanthramides (AVs) are the phytochemicals found in cereals exclusively in oats. These are widely known natural substances that have antioxidant properties. The free radical deactivation potential of the eight AVs against five reactive species has been studied in physiological pH. At physiological pH, the radical quenching processes were studied using the sequential proton loss followed by electron transfer (SPLET) from the phenolic hydroxyl groups. Using density functional theory (DFT) computations, theoretical studies have been carried out in the gas phase and aqueous solution at M06-2X/6-31 + G (d,p) level of theory. The free radical scavenging ability of the studied AVs was analyzed by using conceptual density functional theory-based parameters and electrostatic potential analysis. By examining the hydrogen atom and electron affinities of each reactive species, the relative destructive potential of each has been compared. The electron transfer capabilities between the studied compound and reactive species were identified by utilizing the ionization energy and electron affinity plots. Additionally, by calculating the redox potentials and equilibrium constants for the entire process in the aqueous solution, the viability of scavenging the free radical species by selected AVs (both in neutral and mono-deprotonated) has been investigated. From the analysis, the neutral as well as the mono-deprotonated form of AVs are found to scavenge • OH and • OOH, and • NO 2 radicals effectively, while they are inefficacious toward the O 2 •‾ and • NO radicals. Graphical Abstract