Site-Selective Dehydroxy-Chlorination of Secondary Alcohols in Unprotected Glycosides

Abstract

To circumvent protecting groups, the site-selective modification of unprotected glycosides is intensively studied. We show that site-selective oxidation, followed by treatment of the corresponding trityl hydrazone with tert- butyl hypochlorite and a H atom donor provides an effective way to introduce a chloride substituent in a variety of mono- and disaccharides. The stereoselectivity can be steered, and a new geminal dichlorination reaction is described as well. This strategy challenges existing methods that lead to overchlorination.

Site-Selective Modification of (Oligo)Saccharides

“…Blocking of the axial face has also been shown to determine the selectivities in photoalkylation reactions and deoxy-chlorination reactions. 16 , 17 The same mechanism is likely determining the selectivity in the recently reported photoalkylation of myo-inositol. 18 Recently, a second catalyst system was developed, which converts β-glucosides into β-allosides ( Scheme 1 B).…”

“…As for the reductions of 3-ketoglucosides ( vide supra ), H-atom abstraction by the C3-centered radical will preferentially occur from the equatorial face, the axial face being blocked by the anomeric substituent (Scheme A). Blocking of the axial face has also been shown to determine the selectivities in photoalkylation reactions and deoxy-chlorination reactions. , The same mechanism is likely determining the selectivity in the recently reported photoalkylation of myo-inositol . Recently, a second catalyst system was developed, which converts β-glucosides into β-allosides (Scheme B).…”

Mechanism-Guided Design of Robust Palladium Catalysts for Selective Aerobic Oxidation of Polyols

“…We propose that steric interactions between the bulky L 3 ligand and glycoside substrates may overcome intrinsic electronic factors that favor oxidation at C3 . The dependence of chemoselectivity on the ligand structure observed here therefore offers an opportunity to obtain rare oxidized glycosides, which can undergo further functionalization to yield valuable carbohydrate products. ,− …”

Site-Selective Electrochemical Oxidation of Glycosides

“…Over the past years, significant progress has been made in the site-selective modification of unprotected and partially protected carbohydrates. − Regioselective oxidation is particularly noteworthy due to the versatile derivatization of respective ketones or carboxylic acids. − TEMPO-mediated oxidation of glycopyranosides leads to selective oxidation of the primary C6 hydroxy group, most often producing the corresponding uronic acids. − Palladium-catalyzed oxidation shows a strong preference for the secondary C3 hydroxy group (Figure ). The preference for the C3 over the C2 and C4 position (Figure A) was rationalized based on thermodynamic and kinetic arguments …”

“…This palladium-catalyzed oxidation reaction has shown to be versatile − and scalable; − however, in applications, a metal-free protocol would be advantageous.…”