Total Synthesis of (+)-Melicolone K Enabled by a Late-Stage Programmed C–H Functionalization
Abstract
An asymmetric total synthesis of (+)-melicolone K is described for the first time. The strategy features a late-stage programmed C–H functionalization, which comprises a Rh(II)-catalyzed γ-C(sp 3 )–H amination and a newly formed cyclic sulfamate ester-directed γ-C(sp 3 )–H prenylation through a formal (4 + 2) cycloaddition/reductive ring-opening process. By incorporation of a Sharpless asymmetric dihydroxylation, a Wolff ring contraction, and a Ti(III)-mediated radical cyclization, our approach rendered concise and efficient access to this flagship prenylated natural product with good enantio- and diastereocontrol. The direct, single-step prenylation protocol developed in this work paves the way for streamlined syntheses of the prenylated natural products.
Fields of Study & Subjects
Catalytic C–H Functionalization Methods
Synthesis and Catalytic Reactions
Advanced Synthetic Organic Chemistry
Publication details
- Journal / source
- Journal of the American Chemical Society
- Publisher
- American Chemical Society (ACS)
- Volume
- 148
- Issue
- 2
- Pages
- 2119–2125
- Publication date
- 9 January 2026
- Language
- EN