TIPS ether

N HCl, EtOH, 90°, 15 min, 100% yield. HCl in a variety of other concentrations has also been used to cleave the TIPS ether. 

From aTHP ether TBDMSH, CH2CI2, Sn(OTf)2, it, 1 h, 78% yield. TIPS ethers are prepared analogously. ... 

Notes, (a) TIPS ethers are more stable in base than TBDMS ethers. 

According to results published by Fer6zou and coworkers, the iV,iV-diisopropylcarba-moyl group of homoaldol adducts can be directly attacked by slim nucleophiles such as lithium ethynylide or excess methyllithium (equation 98) . The TIPS ether 359 was treated with three equivalents of methyllithium to yield [via the (Z)-enolate 360] the aldehyde 361. Trapping of 360 by TBSCl gives rise to the synthetically valuable (Z)-silyl enol ether 362. 

Silyl ethers that have been used in solid-phase synthesis include TES, TIPS, TBS, and TBDPS ethers. Polystyrene-bound phenols can be converted into TIPS ethers by treatment with TIPS-OTf/imidazole in DMF for 5 min [105], These silyl ethers are stable towards bases and weak acids, but can be selectively removed by treatment with TBAF (Entries 6 and 8, Table 7.8) or pyridinium hydrofluoride (THF, 25 °C, 15 h [24,75,106]). 

However, there is one report of partial hydrolysis of a TIPS ether promoted by the... 

An enone obtained by IBX oxidation suffers an in situ intramolecular Diels-Alder reaction. Dess-Martin periodinane produces partial desilylation of the TIPS ether due to its slightly ... 

The merits of TIPS ether protection have been reviewed66, with emphasis on those reactions where the incremental structural difference between TIPS and other commonly used trialkylsilyl groups leads to results quite different from those obtained with TMS or TBDMS ethers. 

The resulting propargylic alcohol is protected as TIPS ether by a standard procedure using the corresponding silyl chloride and imidazole in DMF. Optionally the more reactive silyl triflate and 2,6-lutidine may be employed in order to shorten the reaction time. Under acidic conditions TIPS and TPS are nearly stable protecting groups. Therefore the TBS ether is selectively cleaved with acetic acid even in presence of the acetal moiety.13 Subsequent reaction with iodine and triphenylphosphine, known as the Appel reaction14, provides the desired iodide 4. 

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. 

TIPS ether) A silyl ether of formula R -O-Sid-Prh commonly used to protect alcohol groups. Formed from an alcohol with TIPSC1 and a tertiary amine. Deprotected using aqueous fluoride salts, (p. 645)... 

Such is the lability of TMS ethers, that they can usually be removed selectively in the presence of other members of the silyi ether family. For example, in Car-reira s synthesis of Zaragozic Acid C,5 a tertiary TMS ether was removed in the presence of a primary fetf-butyldimethylsilyl (TBS) ether with chloroacetic acid in methanol [Scheme 4.2] moreover, tertiary TMS ethers can be removed in the presence of primary triisopropyl (TIPS) ethers using pyridinium /Moluene-sulfonate in methanol [Scheme 4.3).6... 

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. 

During a synthesis of the marine antitumour agent Sarcodictyin A, selective removal of a secondary and a tertiary TES ether in the presence of a primary TIPS ether was effected by treatment with 5 equivalents of triethylamine trihy-drofluoride (Et3N 3HF)26 in THF at room temperature [Scheme 4,21 ].6... 

Acetic acid in aqueous THF removes TBS ethers at room temperature whilst leaving rm-butyldiphenylsilyl [Scheme 4.29]42 and TIPS ethers Scheme 4.30]43 unscathed. A convenient method for removing TBS ethers entails stirring the substrate in methanol with a sulfonic acid resin such as Dowex 50W-X8. The advantage here is that no aqueous workup is required the resin is simply filtered off at the end of the reaction and the product isolated by evaporation of... 

Occasionally stronger acids are used to remove TBS ethers. For example, in a synthesis of os-9,IO-dehydroepothilone Dt White and co-workers54 removed two TBS protecting groups in the last step with 50% trifluoroacetic acid in di-chloromethane at 0 °C [Scheme 4.36]. Scheme 4.37 shows that selective removal of a primary TBS ether in the presence of a tertiary TBS ether as well as a primary and secondary TIPS ethers is feasible using camphorsulfonic acid in a 1 1 mixture of methanol and dichloromethane at 0 DC.5S,S6... 

During a synthesis of Hennoxazole, Wipf and Lim97 found that Lithium hydroxide at 90 3 C offered a convenient method for removing a TBS ether in the presence of a TIPS ether [Scheme 4.59], This is a rare example of the use of basic hydrolysis in selective alkyl silyl ether deprotection. 

TBDPS ether in the presence of a secondary TBS ether and a secondary TIPS ether [Scheme 4.75].131 In the final step of the synthesis, the remaining TBS and TIPS ethers were cleaved with 6% HC1 in THF at room temperature for 72 h. 

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-... 

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... 

Trichloroalane in dichloromethane cleaves isopropyl aryl ethers leaving methyl aryl ethers intact. A variety of functional groups (aryl halides, 1,1-dihaloalkenes, aldehydes and acetates) withstand the reaction conditions but alkynes and TIPS ethers do not survive. Scheme 4 110 illustrates an application of the reaction to a synthesis of the Fagaronine alkaloids,201 TVichloroborane in dichloromethane may also be used for the deprotection of isopropyl ethers.202... 

Aryl triflate 13 is obtained by reaction of silyl ether 12 with CsF, CS2CO3 and Comins reagent at room temperature. Under these reaction conditions the TIPS-ether is cleaved to provide the corresponding phenolate, which undergoes reaction with Comins reagent to give triflate 13 in a one-pot protocol. 

TBS- vs. TIPS- ethers as protecting groups in the anomeric iithiation of giycais... 

TIPS ethers are cleaved under the same conditions as those used for TBS ethers but longer reaction times are frequently necessary consequently TBS ethers can be removed selectively in many cases. 

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