Cosolvent-Promoted O-Benzylation with Silver(I) Oxide: Synthesis of 1′-Benzylated Sucrose Derivatives, Mechanistic Studies, and Scope Investigation

Abstract

A cosolvent-promoted O-benzylation strategy with Ag2O was developed. The cosolvent consisting of CH2Cl2 and n-hexane can not only improve the reaction solubility for carbohydrates but also increase the benzylation efficiency. The formation of byproducts is greatly inhibited in the developed method. This method is simple, mild, and highly effective, and numerous 1'-benzylated sucrose derivatives were prepared including a photoreactive (trifluoromethyl)phenyldiazirine-based sucrose. The mechanisms of benzylation with primary and secondary benzyl bromides were also elaborated. Furthermore, the application scope with alcohols, glucose, and ribose derivatives was investigated.

Programmable one-pot synthesis of heparin pentasaccharides enabling access to regiodefined sulfate derivatives

“…At this point, we came across the co-solvent promoted O -benzylation using Ag 2 O/BnBr reported by Hashimoto and co-workers. 32 Thus, O -benzylations of 26a and 26b were performed under Hashimoto’s reaction conditions to furnish 27a and 27b , respectively, in excellent yields ( Scheme 5 ). On the other hand, the 6- O -Lev ester in 27b was removed using hydrazine acetate in a mixture of MeOH and THF to give pentasaccharide 28 in a good yield.…”

Synthesis of α-D-GalpN3-(1-3)-D-GalpN3: α- and 3-O-selectivity using 3,4-diol acceptors

“…Using the 6- O -Bn-protected variant ( 2 in Scheme 1 ), a 1:2 mixture of the desired vs migrated product could be obtained. When using the more bulky 6-OTBDPS as protective group ( 1 in Scheme 1 ) and benzylation with freshly prepared Ag 2 O and BnBr in the solvent mixture CH 2 Cl 2 /cyclohexane 1:4 as described by Wang et al [ 39 ], a 91% isolated yield of the migrated product, i.e., 3- O -Bn, 4- O -Bz, was obtained ( Scheme 1 ).…”

Optimization of sucrose 1’-position modification with 3-(trifluoromethyl)diazirinyl benzylbromide derivatives for photoaffinity labeling

“…Although excess amounts of benzyl alcohol derivative (up to 10 eq) and Ag 2 O (up to 15 eq) were subjected to the reaction, no desired product was observed at any conditions (Table 1 Entries 1-4). To compare these synthetic conditions, the reaction with 1'-OH acetylsucrose 3 19,21,22 (0.075 mmol) and diazirinylbenzyl bromide derivative 5 20 (2 eq) in the presence of Ag 2 O (3 eq) was conducted in CH 2 Cl (5 mL). The 1'-O-diazirinyl benzyl substituted heptaacetyl sucrose 6 was afford less than 8% at 60 °C (Table Entry 5).…”