Catalytic Dinuclear Nickel Spin Crossover Mechanism and Selectivity for Alkyne Cyclotrimerization

Homodinuclear transition-metal catalysts with a direct metal–metal bond have the potential to induce novel reaction mechanisms and selectivity compared with mononuclear catalysts. The dinuclear (^{<i>i</i>‑Pr}NDI)­Ni₂(C₆H₆) (NDI = naphthyridine-diimine) complex catalyzes selective cyclotrimerization of monosubstituted alkynes, whereas mononuclear Ni catalysts generally give cyclotetramerization of alkynes. Density functional theory calculations reveal that the homodinuclear Ni–Ni catalyst induces a spin crossover mechanism that involves metallacyclopentadiene and nonclassical bridging metallacycloheptatriene intermediates. The cis configuration of the nonclassical bridging metallacycloheptatriene Ni–vinyl bonds results in alkyne cyclotrimerization by fast reductive elimination. This dinuclear mechanism differs from previously reported mononuclear Ni mechanisms and provides an explanation for cyclotrimerization versus cyclotetramerization selectivity and arene regioselectivity

Computational Transition-State Design Provides Experimentally Verified Cr(P,N) Catalysts for Control of Ethylene Trimerization and Tetramerization

Computational design of molecular homogeneous organometallic catalysts followed by experimental realization remains a significant challenge. Here, we report the development and use of a density functional theory transition-state model that provided quantitative prediction of molecular Cr catalysts for controllable selective ethylene trimerization and tetramerization. This computational model identified a general class of phosphine monocyclic imine (P,N)-ligand Cr catalysts where changes in the ligand structure control 1-hexene versus 1-octene selectivity. Experimental ligand and catalyst synthesis as well as reaction testing quantitatively confirmed predictions

Synthesis and Computational Studies Demonstrate the Utility of an Intramolecular Styryl Diels–Alder Reaction and Di‑<i>t</i>‑butylhydroxytoluene Assisted [1,3]-Shift to Construct Anticancer <i>dl</i>-Deoxypodophyllotoxin

Deoxypodophyllotoxin is a secondary metabolite lignan possessing potent anticancer activity with potential as a precursor for known anticancer drugs, but its use is limited by scarcity from natural sources. We here report the total synthesis of racemic deoxypodophyllotoxin in seven steps using an intramolecular styryl Diels–Alder reaction strategy uniquely suited to assemble the deoxypodophyllotoxin core. Density functional theory was used to analyze concerted, polar, and singlet-open-shell diradical reaction pathways, which identified a low-energy concerted [4 + 2] Diels–Alder pathway followed by a faster di-<i>t</i>-butylhydroxytoluene assisted [1,3]-formal hydrogen shift

Synthesis and Computational Studies Demonstrate the Utility of an Intramolecular Styryl Diels–Alder Reaction and Di‑<i>t</i>‑butylhydroxytoluene Assisted [1,3]-Shift to Construct Anticancer <i>dl</i>-Deoxypodophyllotoxin

Deoxypodophyllotoxin is a secondary metabolite lignan possessing potent anticancer activity with potential as a precursor for known anticancer drugs, but its use is limited by scarcity from natural sources. We here report the total synthesis of racemic deoxypodophyllotoxin in seven steps using an intramolecular styryl Diels–Alder reaction strategy uniquely suited to assemble the deoxypodophyllotoxin core. Density functional theory was used to analyze concerted, polar, and singlet-open-shell diradical reaction pathways, which identified a low-energy concerted [4 + 2] Diels–Alder pathway followed by a faster di-<i>t</i>-butylhydroxytoluene assisted [1,3]-formal hydrogen shift

Synthesis and Computational Studies Demonstrate the Utility of an Intramolecular Styryl Diels–Alder Reaction and Di‑<i>t</i>‑butylhydroxytoluene Assisted [1,3]-Shift to Construct Anticancer <i>dl</i>-Deoxypodophyllotoxin

Deoxypodophyllotoxin is a secondary metabolite lignan possessing potent anticancer activity with potential as a precursor for known anticancer drugs, but its use is limited by scarcity from natural sources. We here report the total synthesis of racemic deoxypodophyllotoxin in seven steps using an intramolecular styryl Diels–Alder reaction strategy uniquely suited to assemble the deoxypodophyllotoxin core. Density functional theory was used to analyze concerted, polar, and singlet-open-shell diradical reaction pathways, which identified a low-energy concerted [4 + 2] Diels–Alder pathway followed by a faster di-<i>t</i>-butylhydroxytoluene assisted [1,3]-formal hydrogen shift

Practical Singly and Doubly Electrophilic Aminating Agents: A New, More Sustainable Platform for Carbon–Nitrogen Bond Formation

Given the importance of amines in a large number of biologically active natural products, active pharmaceutical ingredients, agro­chemicals, and functional materials, the development of efficient C–N bond-forming methods with wide substrate scope continues to be at the frontier of research in synthetic organic chemistry. Here, we present a general and fundamentally new synthetic approach for the direct, transition-metal-free preparation of symmetrical and unsymmetrical diaryl-, aryl­alkyl-, and dialkyl­amines that relies on the facile single or double addition of readily available <i>C</i>-nucleo­philes to the nitrogen atom of bench-stable electro­philic aminating agents. Practical single and double polarity reversal (i.e., umpolung) of the nitrogen atom is achieved using sterically and electronically tunable keto­malonate-derived imines and oximes. Overall, this novel approach represents an operationally simple, scalable, and environmentally friendly alternative to transition-metal-catalyzed C–N cross-coupling methods that are currently used to access structurally diverse secondary amines