Protection triisopropylsilyl chloride

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. 

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. 

During a monumental synthesis of Strychnine, the Overman group encountered difficulties with the simple selective protection of the primary alcohol function in diol 87,1 as its TIPS ether [Scheme 4.89].143 The best method involved treatment of diol 87.1 with 2 equivalents of triisopropylsilyl chloride and 2.2 equivalents of 1,1,3,3-tetramethylguanidine at 0 °C in N-methylpyrrolidinone until the diol could no longer be detected by thin layer chromatography. This treatment... 

Triisopropylsilyl chloride (TIPS-Cl) is an excellent reagent for the selective protection of a primary OH in the presence of a secondary OH group. ° A simple and efficient method for silylation of alcohols and phenols is using TIPS-Cl and imidazole under microwave irradiation. The TIPS group is stable under a wide range of reaction conditions, such as acid and basic hydrolysis, and toward powerful nucleophiles. 

Protection of the 3 - and 5 -Hydroxy Functions. The reagent design was based upon the fact that triisopropylsilyl chloride reacts 1000 times faster with primary alcohols than secondary alcohols. Thus in the case of 3, 5 -dihydroxy nucleosides the reagent initially silylates at the 5 -position. This is then followed by intramolecular reaction with the secondary alcohol at the 3 -position to give the doubly protected derivative (eq 1). ... 

Protection of Hydroxyl Groups. Triisopropylsilyl chloride (TIPSCl) continues to be widely used as the means of introducing the TIPS protecting groups onto alcohols. The steric bulk of the three isopropyl groups on the silicon atom provides considerable stability under acidic and basic conditions and allows selective removal of smaller, more labile silyl groups in the presence of TIPS ethers.i2.i3... 

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. 

C2 silylation as a protecting group strategy for oxazoles has historically been difficult due to the preferential oxophilicity of standard silyl chlorides protection of the ring opened oxygen atom typically predominates rather than protection of the C2 carbon atom. Miller has shown that treatment of imsubstituted oxazole with -BuLi followed by triisopropylsilyl triflate yields C2-silylated oxazole in near quantitative yield. Furthermore, this protected oxazole is stable to nonacidic aqueous workup and... 

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