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

• Published in: Chemistry : a European journal 2023-12, Vol.29 (69), p.e202302406-n/a
• Main Authors: Tague, Andrew J., Hoang Pham, Quoc, Richardson, Christopher, Pyne, Stephen G., Hyland, Christopher J. T.
• Format: Article
• Language: English
• Subjects: 2-nitro-1,3-enyne; Alkynes; Chemical reactions; Chemistry; Cycloaddition; Dipoles; Enantiomers; Nitrogen; Palladium; Single crystals; Stereochemistry; Stereoselectivity; tetrahydroquinoline; vinyl benzoxazinanone
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.202302406

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.