Synthetic approaches to phosphasugars (2-oxo-1,2- oxaphosphacyclanes) using the anomeric alkoxyl radical β‑fragmentation reaction as the key step

Hernández-Guerra, Daniel and Kennedy, Alan R. and León, Elisa I. and Martín, Ángeles and Pérez-Martín, Inés and Rodríguez, María S. and Suárez, Ernesto (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). pp. 4861-4880. ISSN 0022-3263

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    Abstract

    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.