Christopher J. T. Hyland

A formal palladium‐catalyzed decarboxylative (4+2) cycloaddition reaction between 4‐vinylbenzoxazinanones and 2‐nitro‐1,3‐enynes has been developed to produce highly valuable, densely functionalized tetrahydroquinolines in moderate to excellent yields with high diastereoselectivity under mild reaction conditions. The optimised protocol tolerates a range of substituted 2‐nitro‐1,3‐enynes, which represent an under‐utilized class of dipolarophile for transition‐metal catalyzed cycloadditions. The employed reaction methodology facilitates efficient cycloaddition with both N ‐H‐ and N ‐Ts‐4‐vinylbenzoxazinanone dipole precursors. The stereochemistry of the major and minor diastereomeric (4+2) cycloadducts was determined by single crystal X‐ray analyses. A mechanistic rationale for the high intrinsic diastereoselectivity and preliminary enantioselective experiments are also presented. The tetrahydroquinoline cycloadduct products feature numerous pendant functionalities, including a vinyl handle, an internal alkyne motif and a nitro functionality (which functions as a latent C‐3 nitrogen substituent) for further synthetic manipulations.

Density functional theory (DFT) has provided a detailed mechanistic picture for the redox neutral nickel(II)‐catalyzed arylative cyclization reactions of a tethered allene‐ketone with arylboronic acids. A mechanistic rationale for the high diastereo‐ and enantioselectivity achieved experimentally at high reaction temperature was uncovered through modeling the reaction with a chiral ligand and the predicted stereochemical outcome corroborates with experimental results. An unprecedented mechanism for the base‐free organoboron transmetalation was revealed and the regioselectivity of migratory insertion of tethered allene‐ketones as well as the stability of the possible allylnickel isomers (σ‐allyl vs π‐allyl) were clarified. The multifaceted nature of the reaction is revealed with certain elementary steps preferring cationic compared to the neutral state.