Deprotection of silyl ethers

T. D. Nelson and R. D. Crouch, Selective Deprotection of Silyl Ethers, Synthesis, 1031 (1996). 

The oxidative deprotection of silyl ethers, such as the TBDMS ether, has been reviewed. " ... 

Deprotection of silyl ethers can be accomplished by using a variety of reagents such as TBAF, BF3-OEt2, alkali metal tetrafluoroborate and HF. Here, PPTS is used to distinguish the TBS from the TPS group. Thus, the rearranged 27 cleaves selectively the least bulky silyl group to form mono-protected 8.12... 

In our earlier discussion of the use of fluoride in the deprotection of silyl ethers, the potential for mischief caused by the basicity of various fluoride reagents was noted. However, the basicity of fluoride reagents can be harnessed to good use. A case in point is the easy elimination of 2-tosylethyl esters induced by TBAF in non-aqueous media. The reaction is so fast that /er/-butyldimethylsilyl groups remain intact [Scheme 6.98].2> ... 

Silyl ethers are renowned, and used, for their highly selective deprotection with fluoride sources (Method 14) as mentioned above, but selecting between different silyl ethers under these conditions is not always reliable unless the silyl alkyl substituents are sufficiently different. However, deprotection of silyl ethers of l°-alcohols, in the presence of similarly protected 2°-alcohols, is routinely possible under either acidic or basic conditions [45]. 

Similarly, the sonolysis of carbon tetrachloride in methanol gives hydrogen chloride used for the fast and selective deprotection of silyl ethers (Fig. 18). A vinylic methoxy group is kept intact under these conditions. Conventional methods require more sophisticated reagents to obtain an equivalent selectivity. Work-up is simplified, and a simple evaporation of the solvent provides the desired products sufficiently pure for most further uses. ... 

Deprotection of Silylated Ethers. TBBDS is also an efficient catalyst for the deprotection of alcoholic and phenolic silyl ethers. In the presence of an aprotic solvent such as dichloromethane and some drops of H2O, the alcohols are isolated in good to excellent yields (eq 10). The reaction is highly chemoselective bacause no halogenation of the aromatic ring occurs, and no overoxidation of the newly liberated alcohol to the corresponding aldehyde is observed. For this reaction again, the... 

For the deprotection of silyl ethers, aq H2Sip6 is superior to aq HF. Fluorosilicic acid is a more potent cleaving agent than HF, allowing its use in stoichiometric or even catalytic quantities (eqs 1 and 2). The lower acid concentrations result In milder reaction conditions that are compatible with several acid labile moieties (see below). 

Sensitive Deprotections. Since the previous review, TASF has emerged as a good alternative to TBAF for the mild deprotection of silyl ethers of acid- and/or base-sensitive corr5>ounds. Side reactions, commonly observed during deprotection using TBAF, include complete decomposition (encountered during the synthesis of amphidinolides and aurisides ), acyl migra-... 

The THP rings contained within the bryostatin family of natural products have also succumbed to synthesis by Michael-type cyclization. Yadav et al. reported the tandem desilylation and conjugate addition to give the B ring of bryostatin 1 [27]. TBAF-mediated deprotection of silyl ether 27 resulted in 67 % isolated yield of 2,6-cis THP 28 (Scheme 8, Eq. 1). Thomas and coworkers described a similar approach on a related substrate to that of Yadav et al. (Scheme 8, Eq. 2) [28]. Cleavage of TES and TMS ethers with HF/pyridine resulted in diol 29, and a subsequent cyclization with catalytic base proceeded stereoselectively to 2,6-cis-4-methylene THP 30 (48 % yield over three steps). 

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