Ethers, triethylsilyl alcohol protection

Another common method for alcohol protection is reaction with RjSiCl to give a silyl ether. Reaction conditions usually involve RjSiCl, with 4-dimethylaminopyridine (DMAP) as the base. Both the ease of preparation of the silyl ether and the stability of the protected species depend on the nature of the R groups. Trimethylsilyl ethers (ROTMS) are very labile and readily removed with water and dilute acid. The triethylsilyl group (ROTES) is a little more robust but may be removed with fluoride ion (the use of fluoride to cleave silyl groups reflects the strength of the Si-F bond). r-BuMejSiCl (TBDMSCl) reacts selectively with... 

In the second step, the resulting alcohol is protected as triethylsilyl ether (TES). 

The epoxide 4.2.1.2 proved resistant to nucleophilic attack, but the diol 4.2.1.1 could be converted into a number of new analogs. These included simple analogs such as various C-6 acyl derivatives 4.2.1.4 (167) but also various derivatives produced by deoxygenation at C-7. Thus diol 4.2.1.1 could be protected as its 2 -(triethylsilyl)ether, converted to its cyclic 6,7-a-thiocarbonate, and deoxygenated to the 7-deoxyanalog 4.2.I.5. Analog 4.2.1.5 can be oxidized to the ketone 4.2.1.6, which can then be reduced to the /5-alcohol 4.2.1.7 (176). Both compounds 4.2.1.5 and 4.2.1.7 were as active as taxol in a tubulin-assembly assay, but were 4 and 10 times less potent than taxol in a cytotoxicity assay with the HCT-116 human colon tumor cell line (176). 

The remainder of the right-hand fragment was prepared (Scheme 5) in accord with our efforts in the theopederin D synthesis. Keto-aldehyde 21, available through the condensation of the enamine of isobutyraldehyde with acetyl chloride, was subjected to a Krische allylation to provide secondary alcohol 22 in 93% ee. Protection as a triethylsilyl ether and exposure to TMSOTf yielded enolsilane 23. The enolsilane was selected as the nucleo-phile for the fragment-coupling aldol reaction based on Evans studies on the influence of various substituents on complex aldol reactions. While the silyloxy group in aldehyde 20 was expected to direct nucleophiles toward the undesired face of the aldehyde, consistent with the extended Felkin model,the methyl group adjacent to the aldehyde was expected to direct the nucleophile to the desired face of the aldehyde, in accord with the... 

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