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.
Keywords: 2-nitro-1,3-enyne; cycloaddition; palladium; tetrahydroquinoline; vinyl benzoxazinanone.
© 2023 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.