Causation in a Cascade: The Origins of Selectivities in Intramolecular Nitrone Cycloadditions

Abstract

The factors controlling chemo-, regio-, and stereoselectivity in a cascade of reactions starting from a bis(cyanoalkenyl)oxime and proceeding via nitrone cycloadditions, have been unravelled through a series of density functional calculations with several different functionals. Both kinetic and thermodynamic control of the reaction cascade are important depending upon conditions. Kinetic control is analysed by the distortion/interaction model and is found to be dictated by differences in distortions of the cycloaddends in the transition states. A new mechanism competing with that originally proposed in the application of these reactions to the histrionicotoxin synthesis is discovered in these studies.

Concerted Amidation of Activated Esters: Reaction Path and Origins of Selectivity in the Kinetic Resolution of Cyclic Amines via N-Heterocyclic Carbenes and Hydroxamic Acid Cocatalyzed Acyl Transfer

“…Relative Gibbs free energy values calculated at IEPCM-CH 2 Cl 2 -M06-2X/6-311+G(d,p)//B3LYP/6-31G(d,p); 32 parenthetical values are gas-phase B3LYP/6-31G(d,p) free energies.…”

Nickel-Catalyzed Cross-Coupling of Photoredox-Generated Radicals: Uncovering a General Manifold for Stereoconvergence in Nickel-Catalyzed Cross-Couplings

“…Relative Gibbs free energy values calculated with SMD-water-(U)M06/6-311+G(d,p)//UB3LYP/6-31G(d) and SMD-water-(U)M06/6-311+G(d,p)//UB3LYP/LANL2DZ (in parentheses). 12 …”

Formal Synthesis of (–)‐Perhydrohistrionicotoxin Using a Thorpe‐Ziegler Cyclization Approach. Synthesis of Functionalized Aza‐Spirocycles

“…These interesting biological properties coupled with the construction of the unusual heterocyclic core of these alkaloids has provided a sustained interest in the community of organic chemists . In the last decade, total or formal syntheses of members of the histrionicotoxin family have been achieved by the application of well‐designed methodologies, such as: SmI 2 ‐induced ring expansion, cross‐methathesis‐hydrogenation, free‐radical induced cyclizations, intramolecular nitrone cycloaddition, dienyne metathesis, and rearrangement of deprotonated aziridines …”