Triisopropylsilyl protecting groups

Control of the absolute stereochemistry was possible starting from the optically active substrate. Initial attempts by protecting the hydroxy function as a j8-oxo ester were unsuccessful146. However, the use of triisopropylsilyl protective group allowed the diastereoselective preparation of the vinylaziridine which was then converted to 6,7-diepicastanospermine140. 

The synthesis of monodeprotected tetraethynylethenes starts from the unsymmetrically protected dibromomethylene derivatives 26a/b that are prepared as shown in Scheme 13-6 for 23 [40-42]. Table 13-2 shows the reaction conditions for the palladium-catalyzed ethynylation to 27a-d and the subsequent monodeprotection to 28a-d. Remarkable is the high-yielding kinetically controlled removal of a trimethylsilyl in the presence of triethylsilyl and triisopropylsilyl protecting groups in the synthesis of 28 b. 

Pyrroles and indoles can be protected with the r-butyldimethylsilyl group by treatment with TBDMSCl and n-BuLi or NaH. Triisopropylsilyl chloride (NaH, DMF, 0°-rt, 73% yield) has been used to protect the pyrrole nitrogen in order to direct electrophilic attack to the 3-position.It has also been used to protect an indole.This derivative can be prepared from the silyl chloride and The silyl protective group is cleaved with Bu4N F , THF, rt or with CF3COOH. 

Silyl-derived protective groups are also used to mask the thiol function. A complete compilation is not given here, since silyl derivatives are described in the section on alcohol protection. The formation and cleavage of silyl thioethers proceed analogously to those of simple alcohols. The Si-S bond is weaker than the Si-O bond, and therefore, sulfur derivatives are more susceptible to hydrolysis. For the most part, silyl ethers are rarely used to protect the thiol function, because of their instability. Silyl ethers have been used for in situ protection of the-SH group during amide formation. The use of the sterically demanding and thus more stable triisopropylsilyl thioether may prove worthwhile. ... 

This caveat could be circumvented with the use of triisopropylsilyl (TIPS) protecting groups (Scheme 2a,b),12 16 or when 6-deoxy glycals (devoid of the C-6 oxygen substituent) are used as substrates (Scheme 2c,d,e).13,17,18... 

The triisopropylsilyl (TIPS) group is introduced under the same conditions as TBS groups.5 Instead of imidazole DMAP can be used, too. Under these conditions only the primary alcohol functionality is selectively protected as TIPS ether. 

With more bulky, non-coordinating N-protecting groups such as triisopropylsilyl (389), lithiation occurs at C-3.344... 

We can also easily convert hydroxyl groups to silyl ethers. Section 14-10B covered the use of the triisopropylsilyl (TIPS) protecting group for alcohols. Similarly, sugars can be converted to their silyl ethers by treatment with a silyl chloride, such as chlorotrimethylsilane (TMSC1), and a tertiary amine, such as triethylamine. 

The most stable common silyl protecting group (triisopropylsilyl or TIPS) has three branched alkyl substituents to protect the central silicon from attack by nucleophiles which would lead to cleavage. All three hindered silyl groups (TBDMS, TBDPS, and TIPS) have excellent stability but can still be removed with fluoride. 

The TES group is the most labile of the common silyl protecting groups, apart from TMS, and can usually be removed in the presence of TBS, triisopropylsilyl (TIPS) and rerf-butyldiphenylsijyl (TBDPS) groups. Selective deprotection of a TES ether using aqueous trifluoroaoetic acid left two TBS ethers and two TIPS ethers intact in the Merck synthesis of the immunosuppressant FK-506 [Scheme 4.19].22 Weaker acids such as H2O-HOAC-THF (3 5 11) at room temperature,33 HF pyridine24 and pyridinium p-toluenesulfonate [Scheme 4.2Q]23 can accomplish similar transformations. 

First conversion of primary alcohol 3 to the ferf-butyldiphenylsilyl ether 15 occurs. In the field of silyl ethers the TPS group as well as the triisopropylsilyl (TIPS) group are the most stable protecting groups against a large variety of reaction conditions - consequently they are frequently used in organic synthesis (see Chapter 2). ... 

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