Mild and Selective Deprotection of tert-Butyl(dimethyl)silyl Ethers with Catalytic­ Amounts of Sodium Tetrachloroaurate(III) Dihydrate

Abstract

A simple and mild method for the removal of tert-butyl(dimethyl)silyl (TBS) protecting groups with catalytic amounts of sodium tetrachloroaurate(III) dihydrate is described. The procedure permits selective deprotection of aliphatic TBS ethers in good to excellent yields in the presence of aromatic TBS ethers, aliphatic triisopropylsilyl ethers, aliphatic tert-butyl(diphenyl)silyl ethers, or sterically hindered aliphatic TBS ethers. Additionally, TBS ethers can also be transformed into 4-methoxybenzyl ethers or methyl ethers in one pot by using larger quantities of the catalyst and a higher reaction temperature.

KHF2: A Mild and Selective Desilylating Agent for Phenol tert-­Butyldimethylsilyl (TBDMS) Ethers

“…21 Catalytic NaAuCl 4 •2H 2 O in MeOH has been used to deprotect four phenolic TBDMS groups, but the method gave a low yield with an electron-deficient phenol. 22 In connection with ongoing work on desilylations of some nucleoside substrates, we found the compounds to be exceptionally sensitive to a variety of conventional fluoride reagents. This necessitated the evaluation of alternate reagents and we have found that KHF 2 in MeOH is a mild reagent for cleavage of phenolic TBDMS groups.…”

“…21 Catalytic NaAuCl 4 ·2H 2 O in MeOH has been used to deprotect four phenolic TBDMS groups, but the method gave a low yield with an electron deficient phenol. 22 …”

Hafnium Triflate as a Highly Potent Catalyst for Regio- and Chemoselective­ Deprotection of Silyl Ethers

“…Generally, 0.1 mol% Hf(OTf) 4 was ideal to selectively remove 1°a lkyl TBS ether in the presence of 2°, 3° alkyl and aryl TBS ethers. However, the presence of other functional groups such as carbamate (20,21,24) required elevated amounts of Hf(OTf) 4 for regioselective removal of 1° or 2° alkyl TBS ether. As an extension of this method, the 5′-O-TBS of fully TBS protected uridine (25) and thymidine (26) was smoothly and selectively removed in high yield with 0.5 mol% Hf(OTf) 4 .…”

“…Compounds 1-46 were prepared according to methods described in the literature. 1,2,21 All reactions were monitored by TLC on plates coated with 0.25 mm silica gel 60 F 254 . TLC plates were visualized by UV irradiation (254 nm) or staining with p-anisaldehyde.…”

“…3 In recent years, metal Lewis acid based methods have emerged as a promising approach for the purpose of efficient and selective deprotection of silyl ethers. Though metal Lewis acids, such as Sc(OTf) 3 , 4 InCl 3 , 5 Ce(OTf) 4 , 6 ZnBr 2 , 7 ZrCl 4 , 8,9 SbCl 5 , 10 21 and Zn(OTf) 2 , 22 have been reported effective for desilylation, it should be noted that, typically, 5-30 mol% of these catalysts is required for the removal of 1° alkyl TBS ethers. Among these metal Lewis acids, only Sc(OTf) 3 and the recently reported NaAuCl 4 •2H 2 O are capable of cleaving TBS ethers at a level lower than 1 mol%.…”