Metal-free synthesis of dihydrofuran derivatives as anti-vicinal amino alcohol isosteres.
Bhargav Gupta NangunuriRajendra P ShirkeMi-Hyun KimPublished in: Organic & biomolecular chemistry (2023)
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.