Transition Metal Catalyzed [π2s + π2s + σ2s + σ2s] Pericyclic Reaction: Woodward–Hoffmann Rules, Aromaticity, and Electron Flow

We have shown that the fundamental step responsible for enantioinduction in the inner-sphere asymmetric Tsuji allylic alkylation is C–C bond formation through a seven-membered pericyclic transition state. We employ an extensive series of quantum mechanics (QM) calculations to delineate how the electronic structure of the Pd-catalyzed C–C bond forming process controls the reaction. Phase inversion introduced by d orbitals renders the Pd-catalyzed [π2s + π2s + σ2s + σ2s] reaction symmetry-allowed in the ground state, proceeding through a transition state with Craig–Möbius-like σ-aromaticity. Lastly, we connect QM to fundamental valence bonding concepts by deriving an ab initio “arrow-pushing” mechanism that describes the flow of electron density through the reaction

Reaction Mechanism, Origins of Enantioselectivity, and Reactivity Trends in Asymmetric Allylic Alkylation: A Comprehensive Quantum Mechanics Investigation of a C(sp³)–C(sp³) Cross-Coupling

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 crossover 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. On the basis of these findings, we highlight a computational framework from which chemically accurate results are obtained and address the current limitations of the decarboxylative asymmetric allylic alkylation reaction

Transition Metal Catalyzed [π2s + π2s + σ2s + σ2s] Pericyclic Reaction: Woodward–Hoffmann Rules, Aromaticity, and Electron Flow

We have shown that the fundamental step responsible for enantioinduction in the inner-sphere asymmetric Tsuji allylic alkylation is C–C bond formation through a seven-membered pericyclic transition state. We employ an extensive series of quantum mechanics (QM) calculations to delineate how the electronic structure of the Pd-catalyzed C–C bond forming process controls the reaction. Phase inversion introduced by d orbitals renders the Pd-catalyzed [π2s + π2s + σ2s + σ2s] reaction symmetry-allowed in the ground state, proceeding through a transition state with Craig–Möbius-like σ-aromaticity. Lastly, we connect QM to fundamental valence bonding concepts by deriving an ab initio “arrow-pushing” mechanism that describes the flow of electron density through the reaction

Multireference Description of Nickel-Aryl Homolytic Bond Dissociation Processes in Photoredox Catalysis

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 that this process is disfavored, with barrier heights of ∼70 kcal mol⁻¹, and highlight important ligand noninnocent and multiconfigurational contributions to excited state relaxation and bond dissociation processes that are not captured with DFT. In the multireference description, photo-triggered Ni(II)–C homolytic bond dissociation occurs via initial population of a singlet Ni(II)-to-bpy metal-to-ligand charge transfer (¹MLCT) 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

Probing Trends in Enantioinduction via Substrate Design: Palladium-Catalyzed Decarboxylative Allylic Alkylation of α-Enaminones

Herein, we report the palladium-catalyzed decarboxylative asymmetric allylic alkylation of α-enaminones. In addition to serving as valuable synthetic building blocks, we exploit the α-enaminone scaffold and its derivatives as probes to highlight structural and electronic factors that govern enantioselectivity in this asymmetric alkylation reaction. Utilizing the (S)-t-BuPHOX ligand in a variety of nonpolar solvents, the alkylated products are obtained in up to 99% yield and 99% enantiomeric excess

Synthetic strategy toward ineleganolide: A cautionary tale

We present a case study to demonstrate how complex molecule synthesis can benefit from quantum mechanics (QM) calculations. Theory is applied in two contexts: testing the chemical intuition used in retrosynthetic planning, along with expediting the resolution of unexpected challenges encountered during the course of the synthesis. From a computational lens, we examine retrospectively the strategies employed and the decisions made during our synthetic efforts toward the diterpenoid natural product ineleganolide. Seemingly logical and robust hypotheses are found to be ill-fated after theoretical investigation. Prior knowledge of these issues may have potentially saved valuable time and resources during our synthetic efforts. This cautionary tale suggests that synthetic campaigns can benefit from computational evaluation of synthetic plans

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Multi-messenger Observations of a Binary Neutron Star Merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ∼ 1.7 {{s}} with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of {40}-8+8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 {M}ȯ . An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ∼ 40 {{Mpc}}) less than 11 hours after the merger by the One-Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ∼10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ∼ 9 and ∼ 16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC 4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta.</p