Selective Deprotection of Silyl-Protected Phenols Using Solid NaOH and a Phase Transfer Catalyst

Aryl silyl ethers can be deprotected to yield phenols in good to excellent yields using a biphasic system of 10 equivalents of NaOH and catalytic Bu4NHSO4 in 1,4- dioxane. Alkyl silyl ethers prepared using a variety of silyl protecting groups survive under these conditions, allowing selective deprotection of silyl-protected phenols in the presence of silyl-protected alcohols. © 1999 Elsevier Science Ltd. All rights reserved. Protection/deprotection protocols using silyl protecting groups are among the most widely used methods for temporarily masking alcohols. 1,2 As synthetic targets have become increasingly complex, methods to selectively remove one such silyl group in the presence of another have been developed. 3 Although discrimination between two silyl ethers derived from alcohols is common, relatively few techniques have been developed to deprotect aryl silyl ethers in the presence of alkyl silyl ethers. 3 Although camphorsulfonic acid / methanol 4 and aqueous DMSO 5 have been used to cleave aryl TBS ethers in the presence of alkyl TBS ethers, a survey of the methods reported to effect selective desilylation of aryl silyl ethers reveals basic conditions to be the norm. 3 Davies has demonstrated that, while the desilylation of the TBS ether of p-cresol in 5% NaOH / 95% MeOH has a half-life of 3.5 minutes, the TBS ether of n-hexanol is stable over 24 hours. 6 Among the systematically-studied basic reagents reported to effect selective removal of silyl groups from phenols are: TBAF, 7,8 KF/ 18- crown-6, 8 KF / alumina, 9 K2CO3 / Kryptofix 222,10 K2CO3 / aqueous EtOH 11 and Dowex I-X8 (OH- form). 12 Other methods employing TBAF have been reported as parts of total syntheses. 13-16 Some of these methods require elevated reaction temperatures, 5,10,11,17 lengthy reaction times 5,8 and aqueous workup. We have developed a system that allows selective deprotection of aryl silyl ethers in the presence of alkyl silyl ethers at mild temperatures and with relatively short reaction times and wish to report our findings. Phenols have been reported to undergo selective acylation in the presence of alcohols using powdered NaOH and Bu4NHSO4 in a number of organic solvents. 18 We examined this system as a possible means to deliver OH- ions 19 to silyl-protected phenols in a non-aqueous medium, thereby effecting desilylation. Initial studies (Table 1) on bis-silyl ether 1 showed 10