Triisopropylsilyl ether

It was anticipated all along that the vinylsilane residue could serve as a vinyl iodide surrogate. After protection of the C-14 secondary hydroxyl in 180 in the form of a triisopropylsilyl ether, the vinyltrimethylsilyl function can indeed be converted to the requisite vinyl iodide with AModosuccinimide (NIS) (see 180—>181, Scheme 43). Vinyl iodide 181 is produced stereospecifically with retention of the A17,18 double bond geometry. This transformation is stereospecific since the stereochemistry of the starting vinylsilane and the vinyl iodide product bear a definite relationship to each other.67b 75... 

The completion of the synthesis of 1 only requires two deprotection steps. Hydrogenolysis of the four benzyl ethers, followed by cleavage of the triisopropylsilyl ether with hydrofluoric acid in acetonitrile, provides paeoniflorin (1) in an overall yield of 92 %. 

Triisopropylsilyl ethers iPr3Si-OR TIPS-OR - more stabile to hydrolysis than TMS... 

Triisopropylsilyl ethers are generally cleaved under the same conditions as those used for TBS ethers (i.e.T TBAF-THF, HF-acetonitrile, or HF-pyridine-THK see above) but longer reaction times are frequently necessary consequently, TBS ethers can be removed selectively in many cases. Nevertheless, in a synthesis of Mycotrienol, a secondary TIPS ether was cleaved efficiently and rapidly with p-toluenesulfonic acid in methanol without detriment to a nearby second-... 

Triisopropylsilyl ethers are formed under essentially the same conditions as TBS ethers — i.e. primary or unhindered secondary alcohols are treated with triisopropylsilyl chloride (bp 198 °C/98.5 kPa) in dichloromethane or DMF in the presence of imidazole or DMAP [Scheme 4.85J.138 The TIPS group is too bulky to react with a tertiary alcohol and protection of hindered secondary alcohols can be very slow in which case triisopropylsilyl triflate in the presence of 2,6-lutidine is used.100 However, even with the triflate as the silylating reagent, the reaction can be slow as illustrated by the reaction in Scheme 4.86.61 Triisopropylsilyl triflate is commercially available and it can be easily prepared on a large scale from triisopropylsilane and triflic acid in 97% yield. 

Eliel and coworkers [94] have shown that the occurrence of chelation-control provides a corresponding rate increase in the reactions of a-alkoxyketones with Me2Mg (Figure L24). To observe chelation control and the attendant rate enhancement, the solvent should be a poor Lewis base in order not to compete with the ether substituent The ether R" substituent must not be too bulky methyl or benzyl ethers are highly reactive and selective, while trimethylsilyl ethers are less useful. Triisopropylsilyl ethers react non stereoselectively and at the lowest rate (Figure L25). 

This unusual /3-azido functionalization of triisopropylsilyl ethers is a general reaction, although the best conditions show some variation with the structure of the enol silyl ether. 

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