Stereoselective Synthesis of 2 , 3-unsaturated-O-Glycosides promoted by TeBr 4

The development of synthetic methodologies for the efficient and stereoselective synthesis of glycosides is one of the main interests in carbohydrate chemistry. In this context, the synthesis of 2,3-unsaturated-O-glycosides have attracted considerable attention in this field due to their importance as intermediates in the synthesis of several compounds. One of the important-O-glycosylation method for producing 2,3-unsaturated-O-glycosides, is the Ferrier rearrangement, originally promoted by BF 3 •Et 2 O, which involves a nucleophilic substitution reaction combined with an allylic shift in a glycal. The orientation of the formed glycoside bond, α or β, depends on some combination of control elements, being the most important the ‘kinetic anomeric effect’. A number of other Lewis acids such as InCl 3 , montmorillonite-K10, SnCl 4 , BiCl 3 , FeCl 3 , Sc(OTf) 3 , ZnCl 2 , LiBF 4 , Dy(OTf) 3 , AuCl 3 , CeCl 3 , and ZrCl 4 15


Introduction
The development of synthetic methodologies for the efficient and stereoselective synthesis of glycosides is one of the main interests in carbohydrate chemistry.In this context, the synthesis of 2,3-unsaturated-O-glycosides have attracted considerable attention in this field due to their importance as intermediates in the synthesis of several compounds. 1ne of the important-O-glycosylation method for producing 2,3-unsaturated-O-glycosides, is the Ferrier rearrangement, originally promoted by BF 3 • Et 2 O, which involves a nucleophilic substitution reaction combined with an allylic shift in a glycal. 2 The orientation of the formed glycoside bond, α or β, depends on some combination of control elements, being the most important the 'kinetic anomeric effect'. 3 number of other Lewis acids such as InCl 3 , 4 montmorillonite-K10, 5 SnCl 4 , 6 BiCl 3 , 7 FeCl 3 , 8 Sc(OTf) 3 , 9 ZnCl 2 , 10 LiBF 4 , 11 Dy(OTf) 3 , 12 AuCl 3 , 13 CeCl 3 , 14 and ZrCl 4 15 can be used in the reaction.In addition, oxidizing agents such as DDQ, 16 NIS, 17 iodine, 18 I(Coll) 2 ClO 4 , 19 CAN 20 and HClO 4 on silica gel 21 can promote the reaction.Most of the methods require a large excess of alcohol leading in some cases to an extensive work up. In addition, some have drabacks in generality, yields and diastereoselectivity.
Tellurium tetrahalides (TeCl 4 , TeBr 4 and TeI 4 ) have seen considerable research activity because of their structural versatility and potential utility as synthons in many chemical reactions. 22They can react with both Lewis bases and Lewis acids. 23This amphoteric behavior can be understood in terms of the partially ionic Te-X bonding.
In this way, tellurium(IV) tetrabromide could be the Lewis acid choice to promote the O-glycosylation of glycals 1 to yield 2,3-unsaturated-O-glycosides 2 (Scheme 1).

Results and Discussion
Our initial studies have focused on the development of an optimum set of reaction conditions.In this way, a solution of glycal 1 (1.0 mmol) and propargyl alcohol (1.2 mmol) in CH 2 Cl 2 (10 mL) were treated at room temperature with different amounts of TeBr 4 and the progress of the reaction was monitored by TLC.The results are depicted in Table 1.
In all cases the reaction proceeded smoothly leading to the complete conversion into the 2,3-unsaturated-Oglycoside 2a in high yield and with almost exclusive α-selectivity (Table 1, entries 1-5).It is also interesting to note that when the amount of TeBr 4 was reduced to 0.01 equiv., a significant decrease in the yield and anomeric selectivity was observed (Table 1, entry 6).Next, we explored the scope of the reaction for the synthesis of 2,3-unsaturated-O-glycosides using glycal 1 and various alcohols (Table 2). 27[6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] As shown in Table 2, reactions with aliphatic and alicyclic alcohols required longer reaction times (entries 6-12).This effect was observed before for other catalytic systems. 21he reaction of glycal 1 with t-BuOH is described to be difficult to proceed, 21 but in our case the reaction gave a clean product in high yield and excellent anomeric selectivity (Table 2, entry 10).More reactive alcohols such as allylic, benzylic and propargylic gave better yields and shorter reaction times if compared with aliphatic and alicyclic alcohols (Table 2, entries 1, 2, 3 and 5).The reaction time increased when a homoallylic alcohol was used (Table 2, entry 4).A lower yield was observed when phenol was used as the nucleophile (Table 2, entry 13).This effect was also observed before for other catalytic systems. 4,21e have also examined the influence of the temperature in the reaction.When the reaction was heated under reflux, shorter reaction times were observed if compared with Table 2, without any loss of diastereoselectivity (Table 3).

Table 1 .
Influence of the amount of TeBr 4 in the synthesis of 2,3-unsaturated-O-glycoside, 2a