Silver‐Mediated Cascade Synthesis of Functionalized 1,4‐Dihydro‐2H‐benzo‐1,3‐oxazin‐2‐ones from Carbon Dioxide

• Published in: Angewandte Chemie International Edition Vol. 62; no. 11; pp. e202217803 - n/a
• Main Authors: Li, Xuetong, Benet‐Buchholz, Jordi, Escudero‐Adán, Eduardo C., Kleij, Arjan W.
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 06.03.2023; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Alkylidene; Benzoxazines; Carbamates; Carbon Dioxide; Cascade Reactions; Chemistry; Chemistry, Multidisciplinary; Homogeneous Catalysis; Isomerization; Physical Sciences; Reaction intermediates; Science & Technology; Silver; Homogeneous Catalysis; Silver; 2-OXAZOLIDINONES; PROPARGYLIC ALCOHOLS; CO2; Carbamates; ALKYLIDENE CYCLIC CARBONATES; Cascade Reactions; OXAZOLIDINONES; Carbon Dioxide; FIXATION
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202217803

A conceptually novel catalytic domino approach is presented for the synthesis of highly functional 1,4‐dihydro‐2H‐1,3‐benzoxazine‐2‐one derivatives. Key to the chemoselectivity is a proper design of the precursor to override thermodynamically favored parasitic cyclization processes and empower the formation of the desired product through Thorpe–Ingold effects. The synthetic diversity of these CO2‐based heterocycles is further demonstrated, and the isolation of a reaction intermediate supports an unusual ring‐expansion sequence from an α‐alkylidene, five‐membered cyclic carbonate to a six‐membered cyclic carbamate by N‐induced isomerization. A new CO2 based cascade process has been developed towards pharmaceutically relevant benzoxazine‐2‐one derivatives. The process is empowered by a Ag‐catalyst and shows appreciable structural scope for these target molecules. Mechanistic data and controls are in line with a unique, sequential process that builds on the formation of a five‐membered carbonate intercepted by an N‐centered nucleophile thereby forging a six‐membered cyclic carbamate.