Deprotection of a Silyl Group with Mesoporous Silica

Abstract

The silyl group has been widely used in organic synthesis as a typical hydroxyl protecting group. Especially, the triethylsilyl (TES) group and t-butyldimethylsilyl (TBDMS) group have been used for synthesis of natural products by many researchers since they are comparatively stable against acids and are easy to handle. 1) Although, in general, deprotection of these groups is carried out with acids or fluorine anion, the work-up to remove the acids, especially on a large scale, is tedious and the fluorine anion tends to give rise to side reactions due to its strong basicity. With this background in mind, recently, reaction fields for achieving environmentally benign processes have been designed by many researchers in synthetic organic chemistry.2) Easy work-up is an important factor for achieving an environmentally benign process and the use of heterogeneous catalysts is advantageous. Among them, mesoporous silicas, which possess uniform meso pores, of which pore sizes are 2-50 nm, 3) and narrow pore-distribution and high surface area against amorphous mesoporous materials, such as silica gel or alumina, have been paid much attention due to their potential utility as new heterogeneous catalysts and in providing shape selectivity. In the course of our study on the utility of mesoporous silicas in organic synthesis as solid acid, we have found that their use is feasible for deprotection of silyl groups, and, especially, MCM-41, 4,5) a typical mesoporous silica enables us to deprotect the TES group selectively from the TBDMS group. Selective deprotection of silyl groups can be performed with a variety of liquid protonic and Lewis acids 6-9) ; however, the work-up to remove the acids is tedious as mentioned above. On the other hand, the heterogeneous system is facile from the viewpoint of convenience of the work-up in which mesoporous silicas can be removed by only filtration, and, furthermore, mesoporous silicas have the possibility of recycling. In this paper, we report our detailed study on the scope and limitation of using mesoporous silicas for deprotection of silyl groups. Table 1 shows the results for the deprotection of several silyl ethers (1) of dodecanol with MCM-41 in MeOH. The trimethylsilyl (TMS) and TES ethers (1a, b) were completely deprotected to dodecanol (2); however, the TBDMS and triisopropylsilyl (TIPS) ethers (1c, d) were intact during the indicated reaction time. These results show that selective deprotection of the TES group from the TBDMS group is feasible with the MCM-41/MeOH system. Table 2 shows the results of selective deprotection of the TES group under several conditions by using a typical solid catalyst and TES and TBDMS ether of 1,4-butanediol (3a) as test substrate. In THF, the starting material (3a) was almost intact after stirring for 4 h (entry 1). When acetnitrile, acetone, water, and ethanol were used as a solvent, reactions were sluggish (entries 2-5). On the other hand, methanol was the solvent of choice, and mono-TBDMS ether of 1,4-butanediol (4a) was obtained in 83% yield ...