Switchable Synthesis of Fused Dihydrobenzofuran or Spiro Benzoisoxazole Derivatives Featuring a Migrated or Merged Directing Group
Huihang Hou, Yuanshuang Xu, Jiayi Zou, Chunhua Ma, Xinying Zhang, Xuesen Fan
Abstract
Generating different molecular scaffolds from the same starting materials is an attractive strategy for diversity-oriented synthesis. Presented herein is a switchable synthesis of dihydrobenzofuran-fused indanone or benzoisoxazole spiroindandione based on the cascade reactions of N -phenoxyacetamide with diazo indandione. The selectivity toward different products is expediently manipulated by tuning reaction conditions with the nature of the solvent as a key factor. When the reaction is carried out in DCM, the former is formed through C–H activation (CHA)-initiated [3 + 2] annulation along with acetamide group migration. When the reaction is carried out in DMSO in the presence of a stoichiometric amount of an external oxidant, on the other hand, the latter is generated through CHA-initiated [4 + 1] spiroannulation with directing group retention. In general, this novel protocol features easily tunable selectivity, simple substrates with a broad scope, valuable products with moderate anticancer activity, unique reaction pathways, high atom economy, and ready scalability.