Metal-free synthesis of dihydrofuran derivatives as anti-vicinal amino alcohol isosteres

Dihydrofuran cores are commonly incorporated into synthetically and pharmacologically significant scaffolds in natural product and drug discovery chemistry. Herein, we report a concise and practical strategy to construct spiro-dihydrofuran and amino dihydrofuran scaffolds as anti-vicinal amino alcohol isosteres. Hypervalent iodine (PhI(OAc)(NTs 2 ))-mediated C-H activation of alkynes resulted in two-bond formations with one pi bond cleavage: (i) C(sp 2 )-N(sp 3 ) and O(sp 3 )-C(sp 2 ); (ii) C(sp 2 )-N(sp 3 ) and C(sp 3 )-C(sp 2 ). The metal-free 5- endo-dig oxidative cyclization provided versatile amino 2,3- and 2,5-dihydrofurans bearing the C 5 quaternary carbon. The non-toxicity of all synthesised dihydrofurans was verified via in vitro cell viability assay. Dihydrofuran cores are commonly incorporated into synthetically and pharmacologically significant scaffolds in natural product and drug discovery chemistry.