Nickel-catalyzed hydroxymethylation with α-silicon N -methoxyphthalimides via radical Brook rearrangement
Abstract
-methoxyphthalimide reagent, which acts as a masked hydroxymethyl radical precursor upon reductive N-O bond cleavage and subsequent 1,2-radical Brook rearrangement. The reaction proceeds under mild conditions, exhibits broad functional-group tolerance, and is applicable to a wide range of aryl bromides, iodides, triflates, heteroaryl substrates, and complex bioactive derivatives. Mechanistic studies support a radical pathway involving zinc-mediated single-electron transfer, alkoxyl radical formation, Brook rearrangement, and nickel-catalyzed cross-electrophile coupling. The synthetic utility of this protocol is further demonstrated through gram-scale synthesis and downstream diversification, highlighting its potential for late-stage hydroxymethylation and applications in medicinal chemistry.
Fields of Study & Subjects
Catalytic C–H Functionalization Methods
Radical Photochemical Reactions
Catalytic Cross-Coupling Reactions
Publication details
- Journal / source
- Chemical Science
- Publisher
- Royal Society of Chemistry (RSC)
- Volume
- 17
- Issue
- 19
- Pages
- 9653–9662
- Publication date
- 1 January 2026
- Language
- EN