Enantioselective Construction of Tetrahydroquinazoline Motifs via Palladium-Catalyzed [4 + 2] Cycloaddition of Vinyl Benzoxazinones with Sulfamate-Derived Cyclic Imines

Abstract

A palladium-catalyzed enantioselective [4 + 2] cycloaddition reaction of vinyl benzoxazinones with sulfamate-derived cyclic imines is described, affording the tetrahydroquinazolines bearing several functional rings in high yields (up to 99% yield) with good to excellent diastereoselectivities and excellent enantioselectivities (up to 96% ee). This reaction represents the first Pd-catalyzed asymmetric decarboxylative cycloaddition of vinyl benzoxazinones with imines.

Recent Advances in Enantioselective Pd-Catalyzed Allylic Substitution: From Design to Applications

“…The P -chiral monophosphorus ligand ( R )- L168 induces the enantioselectivity in the final allylic alkylation step. In 2018, Guo reported the first Pd-catalyzed [4+2] cycloaddition of vinyl carbamates with sulfamate-derived cyclic imines ( Scheme 303 b), 738 giving rise to tetrahydroquinazolines containing several functionalized rings in high yields with good to excellent levels of diastereo- and enantioselectivity (dr’s up to >20/1 and ee values up to 96%).…”

An Update of Transition Metal-Catalyzed Decarboxylative Transformations of Cyclic Carbonates and Carbamates

“…For instance, the decarboxylative formation of dihydroquinazolinones through a Pd-catalyzed [4 + 2] cycloaddition using sulfonyl isocyanates as electrophiles was reported by Shi and co-workers [10]. With the introduction of cyclic imines or barbiturate-based olefin reactants, it is feasible to construct highly functionalized quinazolines through decarboxylative cycloadditions [11][12][13]. Most recently, the annulation of deconjugated butenolides or azlactones with vinyl carbamates towards highly functionalized chiral dihydroquinol-2-ones was released by the Xiao group [14].…”

Recent Advances in Metal‐Catalyzed Decarboxylative Reactions of Vinyl Benzoxazinanones

“…reported a Pd‐catalyzed enantioselective [4+2] cycloaddition reaction of vinyl benzoxazinones with sulfamate‐derived cyclic imines to access chiral tetrahydroquinazolines (Scheme 14). [16] The reaction applied to a variety of imines ( 30 ) and vinyl benzoxazinones ( 1 ) bearing various substituents on the different positions of the benzene ring, regardless of whether an electron‐donating or withdrawing group on the benzene ring could be tolerated. Additionally, a slight variation of the N ‐protecting group on vinyl benzoxazine was feasible.…”