Organocatalytic Remote Stereocontrolled (4+2) Annulation of 2‐(4H‐Benzo[d][1,3]oxazin‐4‐yl)acrylates with 4‐Methyleneisoxazol‐5(4H)‐Ones
Year: 2025
Type: article
Abstract: Despite the formidable challenge of concurrently managing both the regiochemistry and stereochemistry of the process, organocatalytic remote stereocontrol has emerged as an appealing approach to establish stereocenters at specified locations distant from reactive functional groups. Herein, we achieved the first organocatalyzed remote stereocontrolled (4+2) annulation of 2‐(4H‐benzo[d][1,3]oxazin‐4‐yl)acrylates with 4‐methyleneisoxazol‐5(4H)‐ones. The nucleophilic attack of a suitable chiral amine to 2‐(4H‐benzo[d][1,3]oxazin‐4‐yl)acrylates generated the key amine‐dipole intermediate, followed by the enantioselective aza‐1,4‐addition of 4‐methyleneisoxazol‐5(4H)‐ones and intramolecular annulation cascade reaction to construct spiro[isoxazole‐4,3’‐quinolin]‐5‐one frameworks bearing continuous three stereocenters. More importantly, different from the well‐established reactions of MBH carbonates, this work successfully established a novel platform for the direct enantioselective synthesis of continuous three stereocenters, inclusive of an ϵ‐stereocenter.
Source: Advanced Synthesis & Catalysis
Authors: Yan Liu, Xuling Chen, Pengfei Li
Institution: Southern University of Science and Technology
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: bronze
Award: G128716482
OpenAlex ID: W4407774109