The photolytic and hydrolytic lability of sisyl (Si(SiMe3)3) ethers, an alcohol protecting group

The tris(trimethylsilyl)silyl (sisyl) group is a photolabile protecting group for primary and secondary alcohols. Sisyl (tris(trimethylsilyl)silyl) ethers 2b–11b of a number of primary and secondary alcohols 2a–11a were prepared in yields ranging from 70–97%. The resulting silyl ethers were stable to aqueous bases, Grignard reagents and Wittig reagents as would be expected for bulky alkoxysilanes. They were also stable to selected fluoride salts including CsF. The sisyl ethers could be cleaved using photolysis at 254 nm in under 30 minutes to give the starting alcohols in yields ranging from 62–95%. The photolytic behaviour of sisyl ethers was examined in more detail using 2,3-dimethyl-1,3-butadiene as a silylene trap. The regiochemistry of the oligosilane fragmentation to silylenes was shown to be dependent upon the alkoxy group. The hydrolytic stability of three sisyl ethers was compared with the analogous t-butyldimethylsilyl ethers. The relative stability of the two silyl groups can be altered by choice of solvent: in acetic acid/water the ease of hydrolysis followed the order ROSi(SiMe3)3 > ROSiMe2t-Bu; the inverse order was observed in CDCl3 using p-TsOH·H2O. Pseudo-first-order rate constants for the acidic hydrolysis of primary, benzylic, and secondary sisyl ethers in AcOH/THF/H2O were determined to be 3.74 × 10−2 s−1, 1.94 × 10−2 s−1, and 1.3- × 10−2 s−1, respectively. The analogous rate constants for the TBS ethers were determined to be 6.04 × 10−3 s−1, 3.53 × 10−3 s−1, and 3.49 × 10−3 s−1, respectively.