Silyl esters hydrolysis

The perfection of this strategy makes use of the L-threonine-derived 2S,ZR acid 61 and tert-h xiy iV-(p-methoxybenzyl)glycinate as the active methylene partner [28d]. After condensation to amide 62, base treatment (LHMDS) induced epoxydation (at 0 °C) and then (25 °C) cyclization. This double inversion mechanism produced a single epimer, 63a, which, through acid 63b, was converted to target 11 by silylation, ester hydrolysis, lead tetraacetate and CAN (or peroxydisulfate) oxidation. 

Wang et al employed the propargyUc Ireland-Claisen rearrangement to initiate a cascade reaction that ultimately deUvered a hexacydic adduct (Scheme 149) [144]. The rearrangement was followed by a Schmittel cydization, radical coupling and prototropic rearrangement to afford the hexacydic add after silyl ester 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. 

A solution of LDA (11 mmol) in THF (30 ml) was cooled to -78°C, and HMPA (CAUTION—CANCER SUSPECT AGENT) (3 ml) then added. To this solution was added dropwise 3-acetoxyoct-l-ene (10 mmol), and then TBDMSC1 (11 mmol) in THF (2 ml) over 5 min. The pale yellow solution was stirred at -78°C for an additional 2 min, and the reaction mixture was allowed to warm to 25DC over 30min. It was stirred at this temperature for a further 2 h, and then quenched with water and pentane. The combined pentane extracts were concentrated, the crude oily silyl ester was dissolved in THF (25 ml) and dilute aqueous HC1 (5 ml, 3 m) and the solution was then stirred for 45 min at 25 °C to complete hydrolysis. The mixture was then poured into aqueous sodium hydroxide (30 ml, I m) and... 

Desilylation model studies were carried out on both the silylated monomer and polymer to develop suitable reaction conditions. The desilylation of the TMSEMA was instantaneous as indicated with GC by the increase in the retention time of the monomer. The desilylation the PTMSEMA was equally facile as determined by NMR spectroscopy Figure 1 shows the disappearance of the -Si(CH3)3 resonance at 0.1 ppm and the appearance of the -OH resonance at 3.3 ppm without detectible ester hydrolysis even after four days. 

The deprotection procedure is based on transesterification of benzyl phosphate into the corresponding silyl ester followed by hydrolysis or alcoholysis. 

Anhydride 150 and trimethylsilyl azide in dioxane yielded an acyl azide, which by thermolysis, and Curtius degradation spontaneously furnished the isocyanate 151 (72CB3958 74CB3533). Anhydride 152 was formed by silyl ester cleavage on hydrolysis [73MI2 90JCS(P1)375]. 

The 1,4,5-oxadiazepine 63 was transformed into 65 by a four-step reaction sequence (1) cleavage of both /-butoxycarbonyl (BOC) and the lactone, (2) acylation of the remote amino group with 2-(trimethylsilyl)ethyloxy-carbonyl chloride (TeocCl), (3) protection of the alcohol functionality with a silyl group, and (4) ester hydrolysis (Scheme 10) C1998AGE2995, 2001CEJ41>. 

Na enolate Zn enolate Enol ether chemistry silyl enol ether Ester hydrolysis Free radical... 

The product of a Ireland-Claisen rearrangement is a silyl ester. However, silyl esters generally are so sensitive toward hydrolysis that one usually does not attempt to isolate them. Instead, the silyl esters are hydrolyzed completely during work-up. Thus, Ireland-Claisen rearrangements de facto afford carboxylic acids and, more specifically, they afford y,5-unsaturated carboxylic acids. 

Fig. 17.32. Oxidative cleavage of an asymmetric ketone with complementary regiose-lectivities. Lactone A is obtained by Baeyer-Villiger oxidation of menthone [2-methyl-5-(l- methylethyl)cyclo-hexanone]. Alternatively, one may first convert menthone into the silylenol ether B and cleave its C=C double bond with ozone to obtain a silyl ester containing an a-methoxyhydroperoxide group as a second functional group (which resembles the unstable structural element of the so-called ether peroxides cf. Figure 1.38). The latter is reduced with NaBH4tothe hydroxylated silyl ester C. The hydroxycarboxylic acid is obtained by acid-catalyzed hydrolysis. It cyclizes spontaneously to give lactone D.

In total synthesis of the structurally unique natural product calcimycin (15), Grieco and others used Ireland-Claisen rearrangement of the ester 17 to synthesize the key intermediate (18)7 (Scheme 1.3g). Monosilylation of the diol 16 followed by treatment with propionyl chloride in pyridine gave rise to the ester 17 in 90% yield. Treatment of 17 with LDA in THF at —78 C, subsequent addition of ferf-butyldimethylsilyl chloride in HMPA, and brief heating of the resulting silylketene acetal provided the corresponding silyl ester. Subsequent hydrolysis of the silyl ester and esterification with diazomethane gave 18 in 90% yield from 17. 

The carboxyl-based TL 1.43 (101) was easily prepared from hydroxymethyl PS resin and a trisubstituted aromatic compound its SP fimctionahzation on the amide carbonyl or on the chlorine atom is followed by cleavage with TMSl (trimethyl silyl iodide) for 72 h at 75 °C to obtain simultaneously ester hydrolysis and decarboxylation to 2-unsubstituted quinazolines. An expansion to other heterocyclic systems is easily foreseeable. 

Danishefsky and coworkers have demonstrated the conversion of lactones to carbocycles by the 3,3-sigmatropic shift of silylketene acetals. Jq the total synthesis of the Fusarium toxin equisetin, for example, keto lactone (138) was converted to its bissilyl derivative (139) by reaction with 2 equiv. of LDA and an excess of TMS-Cl. In situ thermolysis of ketene acetal (1 ) led to a very smooth transformation into ester (140), which was carried on to equisetin (Scheme 26). This methodology was also applied by Schreiber and Smith in the preparation of the cyclohexyl moiety of the immunosuppressive agent FK-506. Ireland-Claisen rearrangement of silylketene acetal (142), prepared by treatment with TBDMS-OTf and triethylamine at low temperature, provided, after hydrolysis of the silyl ester, the carboxylic acid (143) in 71% overall yield (Scheme 27). The strict translation of configuration via a boatlike transition state is typical for this permutation. 

Silylketene acetal (154) was directly prepared from a-silyl ester (153) in xylene at 230 C to give after acid hydrolysis the desired stereoisomer (155) in 72% overall yield with 6 1 stereoselectivity. Silylketene acetals are also obtained by TMS-Cl accelerated conjugate addition of cuprates. The latter method suffers presently from low diastereoselectivities, though it offers the attractive possibility of one-pot formation of two carbon-carbon bonds and three contiguous chiral centers (equation 15). 

Recently, it has been shown that nucleophilic addition of neat dimethyl trimethylsilyl phosphite to serine-derived P-lactonc at I ()() C for 24 h leads specifically to the carboxylic trimethylsilyl ester by preferential transfer of the trimethylsilyl group. A simple aqueous workup induces hydrolysis of the silyl ester to give the N- and P-protected free carboxylic acid ready for activation and coupling. 

After a-metalation, methoxyallene was alkylated with bromo silyl ether 47 to afford 48. A second metalation at the terminus of the allene was quenched sequentially with carbon dioxide and methyl iodide to give the corresponding allenic ester. Hydrolysis of the enol ether and equilibration gave solely the (E)-y-keto acrylate 49 in 30% overall yield. Ketalization then provided 16, which had previously been converted to pyrenophorin (9). ° ... 

Moreover, it must be noted that silylation has still great synthetic potential because of its easy availability and good yields. Thus, using silyl esters is very advantageous for a peptide synthesis without racemisation. The treatment of Z-amino acids or Z-peptides (as p-nitrophenylesters 492 with N-silylamino acid TMS-esters 493 leads to Z-peptide-TMS-esters 494 and after subsequent hydrolysis to Z-peptides 493 in excellent yields (Scheme 71). 

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