Ferrier Glycosylation Reaction Catalyzed by Bi(OTf)₃-Montmorillonite K-10: Efficient Synthesis of 3,4-Unsaturated Sialic Acid Derivatives

Abstract

The reaction of the 4,5-oxazoline derivative of sialic acid with various alcohols was effectively promoted by a catalytic amount of montmorillonite K-10 clay supported Bi(OTf) 3 to produce a variety of 3,4-unsaturated sialic acids via the Ferrier glycosylation reaction in moderate yields.

Facile Diastereoselective Entry to 4β‐Acylamidation of Neu5Ac2en Glycals Using Their N‐Perfluoroacylated Congeners as Key Tools

“…As expected, we obtained amido derivatives 8a and 9 in high yields and with the same stereoselectivity as that observed with 4α-epimer 7. [29,30] At this point, to accomplish the synthesis of the desired free 4β acetamido glycals of DANA 3a, in accordance with our working plan, we attempted the direct reintroduction of the starting acetyl group [15] to afford protected DANA glycal 13 (Scheme 2, route A). Finally, to explain the high β-selectivity observed in the reaction, we performed a modeling study to identify the preferred conformation of the pyranose ring bearing the allylic carbocation (see the Supporting Information).…”

A Simple Synthetic Access to Differently 4‐Substituted Neu5Ac2en Glycals Combining Elements of Molecules with Anti‐Neuraminidase Activity

“…[12,13] The stereoselectivity was not improved by varying the reaction conditions (temperature, solvent, Lewis acid, amount of reagent, etc. Under these conditions, the reaction worked satisfactory with several nucleophiles (Table 2), including sulfonamides ( Table 2, entries 1-3), simple and less simple primary and secondary alcohols ( Table 2, entries 4-10), substituted phenols ( Table 2, entries [13][14], thiols, thiophenols, and amino acidic thiols ( Table 2, entries [15][16][17][18], hydrides ( Table 2, entry 19), and halogen ions ( Table 2, entries [20][21]. Since under milder conditions (lower temperature and less of the Lewis acid), the reaction appeared to take too long without any improvement of the stereoselectivity, we decided to perform our reaction at 40°C, a temperature that would give convenient reaction times, using BF 3 ·Et 2 O (10 equiv.)…”

“…Under these conditions, the reaction worked satisfactory with several nucleophiles (Table 2), including sulfonamides ( Table 2, entries 1-3), simple and less simple primary and secondary alcohols ( Table 2, entries 4-10), substituted phenols ( Table 2, entries [13][14], thiols, thiophenols, and amino acidic thiols ( Table 2, entries [15][16][17][18], hydrides ( Table 2, entry 19), and halogen ions ( Table 2, entries [20][21]. [19] In their pioneering studies on the Ferrier reaction of thiols with neutral hex-2-enopyranosides, A. In all the successful cases, the formation of a 4-substituted glycal was observed, apart from the reactions with cysteine and triethylsilane (TESH), where an S N 2-like reaction was observed with a shift of the double bond to give 2-substituted α glycosides 23a and 24a, respectively ( Table 2, entries 18 and 19).…”

“…To support or exclude this idea, we N-transacylated Ferrier glycosides 29a and 29b [19] to give O-sialosides 30a and 30b, and subjected these compounds to acidic treatment with BF 3 ·Et 2 O (10 equiv., for 15 min) in dichloromethane in separate experiments (Scheme 5). In neither of the reactions did we obtain any glycal deriving from isomerization of the acetalic groups; we observed only the formation of perfluorinated oxazoline 31, which was isolated as such or as 4β-hydroxy FANA glycal 32.…”

“…A solution of oxazoline 5 (100 mg, 0.24 mmol) in CH 3 CN (0.2 mL) was treated with EtSH (100 μL, 1.4 mmol) and Bi(OTf) 3 (5 mg, 0.07 mmol), following the procedure of Ikeda et al, [19] to give a mixture of thioglycosides 33a and 33b. This was separated by rapid chromatography, eluting with hexane/EtOAc (80:20 v/v), to give less polar thioglycoside 33a (38 mg, 33 %), then more polar thioglycoside 33b (59 mg, 52 %).…”