Unprecedented neighboring group participation of C2 N-imidoxy functionalities for 1,2-trans-selective glycosylation

Abstract

Stereoselective glycosylation reactions are important in carbohydrate chemistry. The most used method for 1,2-trans(β)-selective glycosylation involves the neighboring group participation (NGP) of the 2-O-acyl protecting group; nevertheless, an alternative stereoselective method independent of classical NGP would contribute to carbohydrate chemistry, despite being challenging to achieve. Herein, a β-selective glycosylation reaction employing unprecedented NGP of the C2 N-succinimidoxy and phthalimidoxy functionalities is reported. The C2 functionalities provided the glycosylated products in high yields with β-selectivity. The participation of the functionalities from the α face of the glycosyl oxocarbenium ions gives stable six-membered intermediates and is supported by density functional theory calculations. The applicability of the phthalimidoxy functionality for hydroxyl protection is also demonstrated. This work expands the scope of functionalities tolerated in carbohydrate chemistry to include O-N moieties.

Keywords: 1,2-trans-Selective glycosylation; C2 N-Imidoxy; DFT calculations; NGP; O–N functionality.