Trimethylsilyl ethyl Esters

Ethyl (Z)-2-bromo-5-(trimethylsilyl)-2-penten-4-ynoate 2-Penten-4-ynoic acid, 2-bromo-5-(trimethylsilyl)-, ethyl ester, (Z)- (12), (124044-21-9)... 

S,3S)-3-(tert-Butoxycarbonylamino)-2-(phenylselenyl)butanoic Add 2-(Trimethylsilyl)ethyl Ester [40, Boc-(2.S,3.S)-p2,-HAla(aSePh)-OTMSEl l22l... 

Trimethylsilyl)ethyl esters, to protect carboxyl groups, 242... 

Trialkylsilyl protection of carboxylic acids and amines is rare owing to hydrolytic lability. Nevertheless, synthetically useful silicon protecting groups have been developed for these functional groups in which the requisite stability is achieved by incorporating the silicon atom into a 2-(trimethylsilyl)ethyl substituent. The principle is illustrated [Scheme 1.9] by the reaction of 2-(trimethylsilyl)ethyl esters with tetrabutylammonium fluoride the pentavalent siliconate intermediate fragments with loss of ethylene and fluorotrimethylsilane14-15 to liberate a carboxylic arid as its tetrabutylammonium salt. 

Protection of phosphates as 2-(trimethylsilyl)ethyl esters was first developed by the Masamune group as part of their efforts to synthesise Calyculin A with its highly hindered phosphate monoester.77 A diallyi phosphate was evaluated in a model compound, but it was rejected because of incomplete deprotection under Pd(0)-catalysis, The corresponding bis-[2-(trimethylsilyl)ethyl] ester 37 1, on the... 

A panoply of protecting groups was enlisted in the synthesis of Damavaricin by Roush and co-workers.242 Here we show 2 steps [Scheme 8.100] towards the end of the synthesis in which a Teoc group and a 2-(trimethylsilyl)ethyl ester were cleaved simultaneously with TAS-F to liberate an amino group and a carboxyl group that served as partners in a macrolactamisation reaction. 

Since its introduction in 1986315, the 2-(trimethylsilyl)ethylsuifonyl group has been widely adopted in alkaloid, carbohydrate and amino acid chemistry, it is every bit as stable as the arylsulfonyl groups discussed above it is impervious to the ravages of trifluoroacetic add, hot 6 M HC1, trifluoroborane etherate, or 40% HF in ethanol. Nevertheless, under very specific non-reductive conditions, it can be cleaved. The link with 2-(trimethylsilyl)ethyl esters, 2-(trimethylsilyl)ethoxycarbon-y t derivatives, and 2-(thmethylsilyl)ethoxymethyl ethers hardly needs comment. 

The efficiency and specificity of the fragmentation of 3-silyl-substituted derivatives have great value in the design of new protecting groups — a subject treated in greater detail in part 3 of this volume. Carboxylic acids, for example, are easily protected as their 2-(trimethylsilyl)ethyl esters, which are about as stable as ethyl esters under most reaction conditions. However, on treatment with TBAF they frag-... 

Trimethylsilyl)ethyl Ester (TMSE) RC02CH2CH2Si(CH3)3 Formation... 

Synthesis of arenastatin A (172), an extremely potent cytotoxic depsipeptide, involves the coupling of p-alanine 2-(trimethylsilyl)ethyl ester (170) and the D,0-methyltyrosine derivative (171) using DEPC.67,68... 

The mildest reagent for cleaving TBS ethers is pyridinium p-toluenesulfonate (PPTS) in a protic solvent — usually methanol. Under these conditions a primary TBS ether can be cleaved in the presence of a 2-(trimethylsilyl)ethoxy-methyl (SEM) ether and 2-(trimethylsilyl)ethyl ester [Scheme 4.26]. Primary TBS ethers cleave at room temperature but secondary TBS ethers may require elevated temperature. In the transformation shown in Scheme 4.27 two TBS ethers were cleaved in the presence of a TIPS ether." rerf-Butyldiphenylsilyl (TBDPS) ethers are impervious to attack under these conditions as evinced by the selective removal of a primary TBS ether in the presence of an equally exposed primary TBDPS ether in a synthesis of NodRm-IV factors, glycolipids produced by symbiotic fungi that elicit formation of nitrogen-fixing root nodules in legumes [Scheme 4.28]. ... 

Acid sensitivity is a feature of 2-(trimethylsilyl)ethyl esters that has not yet been much exploited but a synthesis of Epoxysorbicillinol serves as a harbinger of a new vein in protecting group chemistry. Care must be taken in a synthesis of Epoxysorbicillinol to prevent aromatisation. Wood and co-workers were able to deprotect the 2-(trimethylsilyl)ethyl ester 94.1 [Scheme 6.94] with excess tri-fluoroacetic acid whereupon decarboxylation ensued to give the iketone derivative 94.2 in 81% yield. The conjugated dienone was then installed by a DDQ oxidation of 94.2 to give Epoxysorbicillinol in a modest 30-40% yield. If the ester deprotection-decarboxylation is attempted with the dienone in place, the yield is very poor. With dilute trifluoroacetic acid. yV-Boc groups can be cleaved in the presence of 2-(trimethylsilyl)ethyl esters. 

The 2-(trimethylsilyl)ethoxycarbonyl groups is rapidly growing in popularity as an amino protecting group whose properties and cleavage are reminiscent of those already described for the coeval 2-(trimethylsilyl)ethyl ester group (see section 6.5.2). 

Tmse ester, 2-(trimethylsilyl)ethyl ester, a carboxy protecting group, cleaved by fluoride ions. 

Deprotection. Deprotection of 2-(trimethylsilyl)ethyl esters using sodium hydride in DMF occurred cleanly in the presence of other sUyl ethers (eq 59). The reactive intermediate is presumed to be traces of anhydrous sodium hydroxide generated from adventitious water in the solvent. 

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