Phenyliodine Bis(trifluoroacetate) (PIFA) as an Excellent Promoter of 2‐Deoxy‐2‐phthalimido‐1‐thioglycosides in the Presence of Triflic Acid in Glycosylation Reactions

Abstract

A combination of phenyliodine bis(trifluoroacetate) (PIFA) and trifluoromethanesulfonic acid was found to be an effective activator for the glycosylation reaction, of which the glycosyl donor was p‐(octyloxy)phenyl 3,4,6‐tri‐O‐acetyl‐2‐deoxy‐2‐phthalimido‐1‐thio‐D‐glucopyranoside or p‐(octyloxy)phenyl 3,4,6‐tri‐O‐acetyl‐2‐deoxy‐2‐phthalimido‐1‐thio‐D‐galactopyranoside. The reaction proceeded with good yields when naturally occurring and derived alkanols, such as cholestanol, (–)‐menthol, 1‐ and 2‐adamantanols and nor‐kauranol, were employed as acceptor substrates. Interestingly, the glycosylation reaction of sterically hindered terpenoid alcohols, such as (–)‐ and (+)‐borneols and (+)‐fenchyl alcohol, with p‐(octyloxy)phenyl 3,4,6‐tri‐O‐acetyl‐2‐deoxy‐2‐phthalimido‐1‐thio‐D‐glucopyranoside afforded the desired β‐glycoside in quantitative yield. Moreover, the present reaction was useful to synthesize disaccharides of which the non‐reducing end was composed of a D‐glucosamine or D‐galactosamine unit.

Glycosylation Reaction of <i>Thioglycosides</i> by Using Hypervalent Iodine(III) Reagent as an Excellent Promoter

“…31,32) Thus, we have recently developed novel methods of hypervalent iodine-induced glycosylation of thioglycoside. 33) Besides our study, a few methods have been reported as for the activation of thioglycosides with hypervalent iodines to date [34][35][36] ; however, activation of disarmed thioglycosides with hypervalent iodines still remains impractical and unavailable in the synthesis of biologically active oligosaccharides. Herein, we now would like to report a new organosulfur participating promoter system in which both the armed and disarmed thioglycoside donors can be activated by using the hypervalent iodine reagent (Chart 1).…”

“…Based on our previous investigation of the glycosylation, 33) we examined the glycosylation reaction of methyl 2-deoxy-2-phthalimido-3,4,6-tri-O-acetyl-1-thio-D-glucopyranoside 1a with 1-O-methyl 2,3,4-tri-O-benzyl-α-D-glucopyranoside 2 using the combination of phenyliodine(III) bis(trifluoroacetate) (PIFA) with various acids. As a result, the reaction with PIFA and trifluoromethanesulfonic acid (TfOH) afforded the best yield (77%).…”

“…On the other hand, odorless p-octyloxylbenzenthiol 33,[37][38][39] was chosen as the source of the aglycon moiety of the 1-thioglycosides to avoid tedious handling of odoriferous organosulfur compounds like methanethiol or benzenethiol, generated during the conventional glycosylation reaction using methyl or phenyl 1-thioglycosides. Based on this information, p-octyloxyphenyl 2-deoxy-2-phthalimido-3,4,6-tri-O-acetyl-1-thio-β-D-glucopyranoside 1c was adopted as the donor glycoside and synthesized by a method reported in the literature.…”

Chemical O‐Glycosylations: An Overview

“…Recently, glycosides with a phthalimido group in the C‐2 position were found to be activated by the hypervalent iodine compound, phenyliodine bis(trifluoroacetate) (PIFA) in the presence of triflic acid . Proper optimization of the reaction conditions of this metal‐free glycosylation afforded the coupled product in significant yields.…”

Regio/Stereoselective Glycosylation of Diol and Polyol Acceptors in Efficient Synthesis of Neu5Ac‐α‐2,3‐LacNPhth Trisaccharide

“…The Neu5Ac-a-2,3-lactosamine donor with a2 -phthalimido group insteado fa2-acetamido group favored the glycosylationr eactionw ith lipids or proteins. [8] Several methods to synthesize LacNPhth and LacNHAc derivatives have been reported (Entries 1-10 in Ta ble1). [7b, 9] These methods can be categorized into two types:o ne using acceptors where both the C3-OH andC 4-OH are unprotected( Entries 1-10 apart from 4a nd 7i nT able 1) and the other using acceptors where only the C4-OH is unprotected( Entries 4a nd 7i n Ta ble 1).…”