Silyl hydrolysis

Human urine D, G, equol, ODMA Acidification, extraction with C18 SPE, anion exchangers (DEAE and QAE), enzymatic hydrolysis, silylation BP-1 (deuterated isoflavones) He GC/MS/EI 2... 

Scheme 11 summarizes the reactions of bis(diisopropylamino)lithiocyclopropenylium perchlorate with a variety of electrophiles. These include acid hydrolysis, silylation, oxidative coupling with iodine to the symmetrical tetraisopropylamino triafulvalene dica-tion, reaction leading to C—C bond formation, with electrophilic allenes to give a zwitterionic dihydrotriafulvenes, with disubstituted cyclopropenylium perchlorate, and... 

High-molecular-weight esters, such as wax esters, steryl esters, triterpenoid esters and triacylglycerols, are often hydrolysed, after which the liberated moieties are GC analysed however, this procedure provides only limited compositional information. The very convenient one-pot small-scale hydrolysis-silylation procedure, applicable to ester-emulsifiers, oils, fats, wax esters and other hydrolysable lipids, has been proposed by the lUPAC (Briischweiler and Hautfeune, 1990). The procedure involves the saponification of esters (ca. 10 mg) in 0.5 N ethanolic KOH solution (0.25 mL) at 80 °C for 3 h, evaporation to dryness in a stream of nitrogen and then silylation of the hydrolysis products. This enables the components of very small samples to be determined (< 0.1 mg). This procedure was used for the hydrolysis of wax esters and triterpenoid esters in potato and eggplant cuticular waxes (Szafranek Synak, 2006 Halinski et al., 2009). A solution of 1-2% (v/v) concentrated sulphuric acid in methanol can be easily used for the transesterification of acyl lipids and the esterification of free fatty acids (Christie, 1994). More procedures for ester hydrolysis and transesterification and for fatty acid esterification are described in detail by Christie (1994). 

The oxidation of higher alkenes in organic solvents proceeds under almost neutral conditions, and hence many functional groups such as ester or lac-tone[26,56-59], sulfonate[60], aldehyde[61-63], acetal[60], MOM ether[64], car-bobenzoxy[65], /-allylic alcohol[66], bromide[67,68], tertiary amine[69], and phenylselenide[70] can be tolerated. Partial hydrolysis of THP ether[71] and silyl ethers under certain conditions was reported. Alcohols are oxidized with Pd(II)[72-74] but the oxidation is slower than the oxidation of terminal alkenes and gives no problem when alcohols are used as solvents[75,76]. 

These hindered silyl ethers are generally more stable to acid hydrolysis than their trityl ether equivalents and can be removed using... 

A large number of silylating agents exist for the introduction of the trimethylsilyl group onto a variety of alcohols. In general, the sterically least hindered alcohols are the most readily silylated, but these are also the most labile to hydrolysis with either acid or base. Trimethylsilylation is used extensively for derivatization of... 

The DTBS group is probably the most useful of the bifunctional silyl ethers. Di-methylsilyl and diisbpropylsilyl derivatives of diols are very susceptible to hydrolysis even in water and therefore are of limited use. 

AcOH, H2O, 89% yield. ° A factor of 400 in the relative rate of hydrolysis is attributed to a conformational effect where the lone pair on oxygen in the silyl ketals does not oveilap with the incipient cation during hydrolysis. 

Silyl esters are stable to nonaqueous reaction conditions. A trimethylsilyl ester is cleaved by refluxing in alcohol the more substituted and therefore more stable silyl esters are cleaved by mildly acidic or basic hydrolysis. 

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 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. ... 

Benzyloxy-2-fluoro-2-methylpropionaIdehyde was prepared in optically active form from (5)-monoethyl 2-fluoro-2-methylmalonate, which had itself been prepared by enzymatic hydrolysis A number of enol silyl ethers or enolates were added to the aldehyde in processes that occur with fair to good diastereoselectivity [6] (equation 6) (Table 2)... 

Half-lives of Hydrolysis of Primary Silyl Ethers... 

EtMgBr, Et20, 90% yield. Under these conditions silyl migration is not a problem, as it was when the typical hydrolysis conditions were used. ... 

Aryl and alkyl trimethylsilyl ethers can often be cleaved by refluxing in aqueous methanol, an advantage for acid- or base-sensitive substrates. The ethers are stable to Grignard and Wittig reactions and to reduction with lithium aluminum hydride at —15°. Aryl -butyldimethylsilyl ethers and other sterically more demanding silyl ethers require acid- or fluoride ion-catalyzed hydrolysis for removal. Increased steric bulk also improves their stability to a much harsher set of conditions. An excellent review of the selective deprotection of alkyl silyl ethers and aryl silyl ethers has been published. ... 

Table 1 gives the relative half-life to acid or base hydrolysis of a number of silylated p-cresols. " ... 

In this series of amides, hydrolysis or aminolysis of a simple ester, cleavage of a silyl groups a cis/trans isomerization, or reduction of a quinone to a hydro-quinone exposes an alcohol that then induces deprotection by intramolecular addition to the amide carbonyl. 

Variations and Improvements on Alkylations of Chiral OxazoUnes Metalated chiral oxazolines can be trapped with a variety of different electrophiles including alkyl halides, aldehydes,and epoxides to afford useful products. For example, treatment of oxazoline 20 with -BuLi followed by addition of ethylene oxide and chlorotrimethylsilane yields silyl ether 21. A second metalation/alkylation followed by acidic hydrolysis provides chiral lactone 22 in 54% yield and 86% ee. A similar... 

The Peterson olefination is a quite modern method in organic synthesis its mechanism is still not completely understood. " The a-silyl organometallic reagent 2 reacts with the carbonyl substrate 1 by formation of a carbon-carbon single bond to give the diastereomeric alkoxides 4a and 4b upon hydrolysis the latter are converted into /3-hydroxysilanes 5a and 5b ... 

This is followed by hydrolysi.s of the ester moieties with potassium carbonate and reesterification of the carboxy moiety with diazomethane to produce intermediate 65. The solitary free alcoholic hydroxyl at C-9 is oxidized with Collins reagent and the silyl ether groups are removed with acetic acid to give enprostil (63) [15]. 

Merck s thienamycin synthesis commences with mono (V-silylation of dibenzyl aspartate (13, Scheme 2), the bis(benzyl) ester of aspartic acid (12). Thus, treatment of a cooled (0°C) solution of 13 in ether with trimethylsilyl chloride and triethylamine, followed by filtration to remove the triethylamine hydrochloride by-product, provides 11. When 11 is exposed to the action of one equivalent of tm-butylmagnesium chloride, the active hydrogen attached to nitrogen is removed, and the resultant anion spontaneously condenses with the electrophilic ester carbonyl four atoms away. After hydrolysis of the reaction mixture with 2 n HC1 saturated with ammonium chloride, enantiomerically pure azetidinone ester 10 is formed in 65-70% yield from 13. Although it is conceivable that... 

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