Cascade reaction of 2-halo-4-alkenyloxazoles with arynes: a switchable divergent synthesis of 2-arylnaphtho[2,1-d]oxazoles, N-acylnaphthylamines, and α-halonaphthalenes

Abstract

A divergent synthesis of 2-arylnaphtho[2,1-d]oxazoles, N-acylnaphthylamines, and α-halonaphthalenes was achieved via a switchable transition-metal-free strategy based on the cascade reaction of arynes with 2-halo-4-alkenyloxazoles. Efforts have been made on the substrate design of 2-halo-4-alkenyloxazoles, in which the halogen atom on the 2-position serves as the versatile handle to unlock multiple reaction possibilities. Concurrently, precise control of the reaction pathway was achieved via the effective modulation of the reaction conditions. Notably, this strategy shows broad substrate compatibility, allowing the use of various 2-halooxazoles, including 2-chloro-, 2-bromo-, and 2-iodo-oxazoles. As a subsequent application development, a series of transformations were successfully realized on naphthoxazoles and polysubstituted naphthalenes, indicating the versatile application potential of the products. The initial bioactivity evaluation in cell-based assays demonstrated that 2-arylnaphtho[2,1-d]oxazoles and N-acylnaphthylamines have considerable antiproliferative activity against both human osteosarcoma cells and non-small cell lung carcinoma cells.