Diastereoselective Pd-catalyzed Decarboxylative (4+2) Cycloaddition Reactions of 4-Vinylbenzoxazinanones and 2-Nitro-1,3-enynes

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. The Pd-catalyzed decarboxylative (4+2) cycloaddition reaction of N-H- and N-Ts-4-vinylbenzoxazinanones with 2-nitro-1,3-enyne dipolarophiles gives valuable tetrahydroquinoline products in high yields with excellent diastereoselectivities. These cycloaddition reactions constitute the first example of a dipolarophile with a single strong activating group (i. e. 2-nitro-1,3-enynes) reacting with 4-vinylbenzoxazinanone derived Pd-stabilized zwitterionic dipoles.image