Multireference electronic structure calculations consistent with known experimental data have elucidated a novel mechanism for photo-triggered Ni(II)-C homolytic bond dissociation in Ni 2,2'bipyridine (bpy) photoredox catalysts. Previously, a thermally assisted dissociation from the lowest energy triplet ligand field excited state was proposed and supported by density functional theory (DFT) calculations that reveal a barrier of ~30 kcal mol-1. In contrast, multireference ab initio calculations suggest this process is disfavored, with barrier heights of ~70 kcal mol-1 , and highlight important ligand noninnocent contributions to excited state relaxation and bond dissociation processes that are not captured with DFT. In the multireference description, phototriggered Ni(II)-C homolytic bond dissociation occurs via initial population of a singlet Ni(II)-tobpy metal-to-ligand charge transfer (1 MLCT) excited state followed by intersystem crossing and aryl-to-Ni(III) charge transfer, overall a formal two-electron transfer process driven by a single photon. This results in repulsive triplet excited states from which spontaneous homolytic bond dissociation can occur, effectively competing with relaxation to the lowest energy, nondissociative triplet Ni(II) ligand field excited state. These findings guide important electronic structure considerations for the experimental and computational elucidation of the mechanisms of ground and excited state cross-coupling catalysis mediated by Ni heteroaromatic complexes.
We utilize quantum mechanics to evaluate a variety of plausible mechanistic pathways for the entirety of the catalytic cycle for asymmetric decarboxylative allylic alkylation of allyl β-ketoesters. We present a mechanistic picture that unites all current experimental observations, including enantioinduction, reaction rate, catalyst resting state, enolate cross-over experiments, water tolerance, and the effects of solvation on inner and outer-sphere mechanisms. Experiments designed to evaluate the fidelity and predictive power of the computational models reveal the methods employed herein to be highly effective in elucidating the reactivity of the catalytic system. Based on these findings, we highlight a computational framework from which chemically accurate results are obtained, as well as address the current limitations of the decarboxylative asymmetric allylic alkylation reaction.
Herein, we report the synthesis and evaluation of 3-hydroxy-1,5-dihydro-2H-pyrrol-2-ones as antibacterial agents against methicillin-resistant S. aureus (MRSA) and methicillin-resistant S. epidermidis (MRSE). Lead compound 38 showed minimum inhibitory concentrations (MICs) of 8 and 4 μg/mL against MRSA and MRSE, respectively. Furthermore, compound 38 displayed a MIC of 8-16 μg/mL against linezolid-resistant MRSA. These molecules, previously underexplored as antibacterial agents, serve as a new scaffold for antimicrobial development.
An enantioselective iridium-catalyzed allylic alkylation of malonates with trisubstituted allylic electrophiles to form all-carbon quaternary stereocenters is reported. This cross-coupling reaction features unprecedented reactivity at ambient temperature, particularly for challenging fully alkyl-substituted allylic electrophiles, and enables the preparation of a wide range of enantioenriched products in up to 93% yield and 97% ee. The products of this transformation can be readily converted to a number of valuable building blocks including vicinal quaternary stereodiads and β-quaternary acids. This method was also used to prepare an enantioenriched intermediate facilitating the asymmetric formal synthesis of the sporochnol family of natural products.
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