biostudies-literatureDong YCamille and Henry Dreyfus FoundationHarvard UniversityNational Institute of General Medical SciencesNIGMS NIH HHS7480-7489https://www.ebi.ac.uk/biostudies/studies/S-EPMC9353666biostudies-literatureUnknown143(19)Intramolecular alkoxylation of C-H bonds can rapidly introduce structural and functional group complexities into seemingly simple or inert precursors. The transformation is particularly important due to the ubiquitous presence of tetrahydrofuran (THF) motifs as fundamental building blocks in a wide range of pharmaceuticals, agrochemicals, and natural products. Despite the various synthetic methodologies known for generating functionalized THFs, most show limited functional group tolerance and lack demonstration for the preparation of spiro or fused bi- and tricyclic ether units prevalent in molecules for pharmacological purposes. Herein we report an intramolecular C-H alkoxylation to furnish oxacycles from easily prepared α-diazo-β-ketoesters using commercially available iron acetylacetonaJournal of the American Chemical SocietyO-Heterocycle Synthesis via Intramolecular C-H Alkoxylation Catalyzed by Iron Acetylacetonate.PMC9353666GM-115815R01 GM115815Zheng SLDong YPorter GJKim JJEssman JZWrobel ATBetley TAfalseO-Heterocycle Synthesis via Intramolecular C-H Alkoxylation Catalyzed by Iron Acetylacetonate.Intramolecular alkoxylation of C-H bonds can rapidly introduce structural and functional group complexities into seemingly simple or inert precursors. The transformation is particularly important due to the ubiquitous presence of tetrahydrofuran (THF) motifs as fundamental building blocks in a wide range of pharmaceuticals, agrochemicals, and natural products. Despite the various synthetic methodologies known for generating functionalized THFs, most show limited functional group tolerance and lack demonstration for the preparation of spiro or fused bi- and tricyclic ether units prevalent in molecules for pharmacological purposes. Herein we report an intramolecular C-H alkoxylation to furnish oxacycles from easily prepared α-diazo-β-ketoesters using commercially available iron acetylacetona2021-01-01T00:00:00Z2021 May2025-04-04T21:34:42.974Z2025-02-19T04:54:01.451ZS-EPMC93536663394985510.1021/jacs.1c02074