The anomeric alkoxyl radical β-fragmentation (ARF) of carbohydrates possessing an electron-withdrawing group (EWG) at C2, promoted by PhI(OAc)2/I2, gives rise to an acyclic iodide through which a pentavalent atom of phosphorus can be introduced via the Arbuzov reaction. After selective hydrolysis and subsequent cyclization, the phosphonate or phosphinate intermediates can be converted into 2- deoxy-1-phosphahexopyranose and 2-deoxy-1-phosphapentopyranose sugars. The ARF of carbohydrates with an electron-donor group (EDG) at C2 proceeds by a radical-polar crossover mechanism, and the cyclization occurs by nucleophilic attack of a conveniently positioned phosphonate or phosphinate group to the transient oxocarbenium ion. This alternative methodology leads to 5-phosphasugars with a 4-deoxy-5-phosphapentopyranose framework. The structure and conformation of the 2-oxo-1,2-oxaphosphinane and 2-oxo-1,2-oxaphospholane ring systems in different carbohydrate models have been studied by NMR and X-ray crystallography.
- alkoxyl radical β-fragmentation
- acyclic iodide
- Arbuzov reaction
- carbohydrate models
Hernández-Guerra, D., Kennedy, A. R., León, E. I., Martín, Á., Pérez-Martín, I., Rodríguez, M. S., & Suárez, E. (2020). Synthetic approaches to phosphasugars (2-oxo-1,2- oxaphosphacyclanes) using the anomeric alkoxyl radical β‑fragmentation reaction as the key step. Journal of Organic Chemistry, 85(7), 4861-4880. https://doi.org/10.1021/acs.joc.0c00059