Protection of alcohols, phenols, thiols and amines, a recurring event in organic synthesis, has received much attention. In particular, protection as a tetrahydropyranyl (THP) ether is often sought after as THP ethers are stable under basic conditions. In addition to protic and Lewis acids, 1 other reagents and catalysts such as iodotrimethylsilane, 2 triphenylphosphine hydrobromide, 3 p-TsOH 4 , BF 3 .Et 2 O, 5 lithium perchlorate, 6 NH 4 Cl, 7 and lithium bromide 8 have been used. However, some procedures have drawbacks such as expensive reagents, high temperatures, strongly acidic conditions and high quantities of reagent. Also there are very few reports of tetrahydropyranylation of thiols 5 and amines. 4 Our main objective is to develop a catalyst for tetrahydropyranylation, applicable to compounds such as thiols, alcohols, phenols and amines under mild reaction conditions.In recent years, MgX 2 (X = Br or I) has gained importance as a Lewis acid for effecting various organic reactions such as nucleophilic additions, 9 cycloadditions, 10 rearrangements, 11 and coupling reactions. 12 Also MgBr 2 has been identified for the hydrolysis of THP ethers. 13 Herein we report a mild and efficient catalyst MgX 2 (X = Br or I), which is used essentially in a neutral medium, for tetrahydropyranylation.Alcohols, thiols, phenols and amines were subjected to tetrahydropyranylation in the presence of MgX 2 (X = Br or I) in dichloromethane at room temperature for 2-9 h to give THP ethers in good yields. The results are summarised in Table 1. All of the products were purified by column chromatography. Note that some sensitive protective {see groups like acetonide (Entry 12) and a bromoalcohol (Entry 11)} remain unaffected under these reaction conditions. The conditions offer good selectivity for mono protected (primary) diols, (Entry 12). These reaction conditions are also applicable to thiols (Entries 8-10) and amines (Entries 4-7).In summary, we have observed MgX 2 to be an excellent catalyst for the protection of alcohols, phenols, thiols and primary amines as tetrahydropyranyl ethers essentially under neutral and mild conditions. The main advantage of our method is that it could be in general applicable to all such compounds and is also compatible with substrates containing acid sensitive functional groups. We anticipate that this method will serve as a useful addition to modern synthetic methodologies.
ExperimentalGeneral experimental details: 1 H and 13 C NMR spectra were recorded on a Varian 300 MHz instrument. Elemental analyses were performed on an EA-1110 instrument.General procedure for the MgX 2 catalysed tetrahydropyranylation of alcohols, thiols, phenols and primary amines. To a solution of compound (1-12) (10 mmol) in dichloromethane (20 ml) was added 3,4-dihydro-2H-pyran (10 mmol) and MgBr 2 (0.27 mmol) or MgI 2 (0.28 mmol) and the solution was stirred for 2-9 hrs at room temperature (Table 1). After completion of the reaction, dichloromethane was removed on a rotary evaporator. The reaction mixture was diluted...
