Mild and Highly Efficient Stereoselective Synthesis of 2,3-Unsaturated Glycopyranosides using La(NO3)3 · 6H2O as a Catalyst: Ferrier Rearrangement

A mild and highly efficient stereoselective reaction of 3,4,6-tri-O-acetyl-D-glucal with a variety of nucleophiles, viz. alcohols, phenols, thiols, thiophenols, and allyl trimethyl silane (TMS), in the presence of 5 mol% of lanthanum(III) nitrate hexahydrate under solvent-free conditions yielded the corresponding 2,3-unsaturated glycopyranosides (pseudoglycals) in excellent yields.

Organic reactions using mild and water-tolerant catalysts received much attention in recent years. They can be conveniently handled and removed from the reaction mixture, making the experimental procedure simple and ecofriendly. Lanthanum(III) nitrate hexahydrate is relatively nontoxic, inexpensive, insensitive to air, and used in various organic transformations, such as chemoselective tetrahydropyranylation of primary alcohols, [25] chemoselective deprotection of acetonides, [26] synthesis of quinazolinones, [27] mild and efficient acetylation of phenols and amines, [28] synthesis of a-amino nitriles, [29] synthesis of benzodiazepines, [30] and N-tert-butoxycarbonylation and N-benzyloxycarbonylation of amines. [31,32] In studying these transformations, it has been observed that the substrates containing other acid labile functional groups, such as TBDMS ethers, some isopropylidene protected diols, and N-tert-Boc-protected amines, were intact in the presence of La(NO 3 ) 3 . 6H 2 O. In continued efforts for utilizing La(NO 3 ) 3 . 6H 2 O, we found that it is an efficient and mild Lewis acid catalyst for the synthesis of 2,3-unsaturated glycopyranosides.

RESULTS AND DISCUSSION
In this article (Scheme 1), we describe a mild and efficient method for the stereoselective synthesis of 2,3-unsaturated glycopyranosides in excellent yields with a-selectivity. This method is very inexpensive, and no special care is required to exclude moisture from the reaction medium. La(NO 3 ) 3 . 6H 2 O is highly oxophilic, forms a labile bond with carbonyl oxygen and initiates the formation of a C-X (X ¼ O, S, Si) bond with Scheme 1.  extended the generality of the reaction with different nucleophiles such as alcohols, phenols, thiols, and allyl TMS at room temperature to give corresponding 2,3-unsaturated glycopyranosides in excellent yields (Table 1). In most of the cases, products were obtained as a mixture of aand b-anomers, with the a-anomer being favored. The ato b-ratio was determined on the basis of integration ratios of the anomeric protons in their corresponding 1 H NMR spectrum. All the products given satisfactory analytical data.
b Isolated yields after column chromatography.
c Ratio was determined on the basis of integration ratios of anomeric protons in its 1 H NMR spectrum.

Typical Experimental Procedure for the Synthesis of 2,3-Unsaturated Glycopyranosides
La(NO 3 ) 3 . 6H 2 O (5 mol%) was added to a mixture of 3,4,6-tri-O-acetyl-Dglucal (1 mmol), alcohols/phenols/thiols/allyl TMS (1.1 mmol), and the reaction mixture was stirred at room temperature under solvent-free conditions for the appropriate time (Table 1). After completion of the reaction as monitored by thin-layer chromatography (TLC), water was added, and extracted into ethyl acetate. The organic layer was dried over anhydrous sodium sulphate and evaporated under reduced pressure. The crude product was purified over silica gel to yield the corresponding 2,3-unsaturated glycopyranosides.