Alcohols triisopropylsilyl

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 method provides a general route to trialkylsilyl triflates and has the advantage of circumventing use of the expensive silver triflate. Triisopropylsilyl triflate in combination with a base, preferably 2,6-lutidine, is effective for silylation of alcohols. 

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. 

Although, the photolysis requires quite short wavelengths (254 nm), the reaction is clean and high-yielding (up to 84% of liberated alcohol) in acetonitrile (a different and nonproductive reaction occurs in benzene) with a variety of primary, secondary, and allylic alcohols, as well with 3 - and 5 -protected nucleosides. The chemical stability is very high, approaching that of triisopropylsilyl (TIPS) in some cases (R2 = Me). 

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. 

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... 

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). ... 

A fourth type of product, a carbamate RNHCOOR , can be obtained from primary or secondary amines, if these are treated with CO, O2, and an alcohol R OH in the presence of a catalyst. " Primary amines react with dimethyl carbonate in supercritical CO2 (see p. 414) to give a carbamate. " Carbamates can also be obtained from nitroso compounds, by treatment with CO, R OH, Pd(OAc)2, and Cu(OAc)2, " and from nitro compounds. " When allylic amines (R2C=CHRCHRNR 2) are treated with CO and a palladium-phosphine catalyst, the CO inserts to produce the p,y-unsa-turated amides (R2C=CHRCHRCONR 2) in good yields. " Ring-expanded lactams are obtained from cyclic amines via a similar reaction (see also, 16-22). Silyloxy carbamates (RNHC02SiR 3) can be prepared by the reaction of a primary amine with carbon dioxide and triethylamine, followed by reaction with triisopropylsilyl triflate and tetrabutylammonium fluoride. ... 

The TIPS group is usually introduced from triisopropylchlorosilane [336], but protection of hindered alcohols can be very slow in which case triisopropylsilyl triflate in the presence of 2,6-lutidine is used [293]. 

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. 

Cyclopropanation of eA o-A-[(lf ,25,3/ ,4S)-2-hydroxy-1,7,7-trimethylbicyclo[2.2.1]hept-3-yl]-3-phenyl-2-propenamide with the diiodomethane/diethylzinc reagent proceeds with moderate diastereofacial selectivity only. However, the corresponding O-triisopropylsilyl-protected compound reacts with excellent but opposite diastereoselectivity the added diethyl tartrate has no influence on the stereoselectivity but only on the rate of the reaction. Similar effects are observed for the related cWo-derivatives of the amino alcohol auxiliary, which induces the opposite absolute configurations at the cyclopropane ring101. 

Asymmetric synthesis of dihydropyridones. 8-Phcnylmcnthol has been used frequently as a chiral auxiliary, but this derivative (1) is more effective as the chiral auxiliary for cnantioselcctivc reactions of N-acylpyridinium salts with organomctallic reagents. Thus 2, prepared by reaction of 4-methoxy-3-(triisopropylsilyl)pyridine with the chloroformate of 1 reacts with the Grignard reagent 3 to give an adduct that on acidic deprotection provides the dihydropyridone 4 in 94% dc. Conversion of the alcohol to a chloride [P(CftH5)j and NCS] followed by treatment with sodium methoxide in methanol cleaves the chiral auxiliary as the methyl carbonate (94% yield) and at the same time effects cyclization to form the chiral bicyclic dihydropyridone 5 in 84% yield. 

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