Site-Selective Debenzylation ofC-Allyl Iminosugars Enables Their Stereocontroled Structure Diversification at the C-2 Position

Abstract

A C-2 regioselective debenzylative cycloetherification/reductive elimination sequence applied to perbenzylated C-allyl iminosugars is described. This NIS/TMSOTf-triggered deprotection was successfully applied to five-, six-, and sevenmembered C-allyl iminosugars including 1,2 cis and 1,2 trans stereoisomers. It allows rapid introduction of structural diversity at the key C-2 position in a stereoselective manner exploiting the anchimeric assistance of the intracyclic N-benzyl group, giving access to the 2-acetamido and 2-fluoro D-gluco configured C-allyl iminosugars and to the epimeric D-manno derivative.

Contributing to the Study of Enzymatic and Chemical Glycosyl Transfer Through the Observation and Mimicry of Glycosyl Cations

“…The free OH of the C-allyl iminosugar 75a was next either epimerized to access the D-manno-configured compound or used to introduce with complete stereocontrol various functions (deoxy, fluoro, acetamido) at C-2 position (Scheme 26). 142…”

Stereoselective Synthesis of Nojirimycin α-C-Glycosides from a Bicyclic Acyliminium Intermediate: A Convenient Entry to N,C-Biantennary Glycomimetics

“… 49 − 51 An apparent reason is the complexity in accessing the C -glycoside precursors in pure diastereoisomeric form. Most of the current protocols involve intramolecular reductive amination 47 , 52 or aza-Wittig cyclization reactions, 47 , 50 , 53 with variable diastereoselectivity outcomes, or the use of 1- C -activated precursors that are themselves obtained as mixtures of diastereomers ( Figure 2 , left panel). 47 , 54 Sharply different, the 5 N ,6 O -oxomethylidenenojirimycin derivative 3 ( 55 , 56 ) (ONJ), a member of the sp 2 -iminosugar subgroup, 57 is a chemically stable and configurationally defined compound that can be functionalized at the pseudoanomeric position via the corresponding acyliminium cation with total α-stereoselectivity ( Figure 2 , right panel).…”

Stereocontrolled Debenzylative Cycloetherification Reaction as a Route to Enantiopure C-Furanosides with Amino Substituents in the Side Chain

“… 16 The process was also used for the selective deprotection of the 2-OH group in a fully benzylated C -allyl glycoside as reported recently by Blériot and co-workers ( Scheme 1 c). 17 …”

“…During the synthesis of higher carbon sugars, we observed a similar rearrangement in which the protected oxygen nucleophile attacked the allylic analog in the S N 2′ mode, which afforded the corresponding tetrahydrofuran derivative (Scheme b) . The process was also used for the selective deprotection of the 2-OH group in a fully benzylated C -allyl glycoside as reported recently by Blériot and co-workers (Scheme c) …”

“…16 The process was also used for the selective deprotection of the 2-OH group in a fully benzylated C-allyl glycoside as reported recently by Bleŕiot and co-workers (Scheme 1c). 17 It seemed reasonable that such processes can be also adapted for the preparation of C-furanose derivatives containing the nitrile or oxime functionality attached directly to the 5-membered ring. The synthesis could be initiated from the corresponding linear carbohydrate derivatives containing the terminal nitrile or oxime groups; this concept is shown in Figure 2.…”