Monosilyl acetals

The aluminoxy acetal intermediates in ester reduction using DIBALH can be trapped with either TMSOTf93 or TMS imidazole94 to give monosilyl acetals (equation 21). 

Silyl enol ethers of cycloalkanones are converted into spiro cydopropylmethanols with CH2l2/ZnEt2 . The reaction of ketene monosilyl acetals with CHBr3/ZnEt2 gives cyclopropanecarboxylic esters (equation 100)". 1-Cyanocyclo pro panecar boxy lie esters... 

Diisobutylaluminum hydride. 13, 115-116 15, 137-138 16, 134-135 17, 123-125 Monosilyl acetals and amines. The DIBALH reduction products of esters can be converted into monosilyl acetals by treatment with TMSOTf-pyridine and those of nitriles into amines by the addition of organolithium reagents. ... 

Alkyl esters can be converted to monosUyl acetals, useful for the synthesis of different homoallylic alcohols or ethers, via reduction and trapping with A-(trimethylsilyl)imidazole (eq 12). Trapping of the reactive aluminum intermediate was less effective with TMS-OTf and ineffective with chlorosilanes. It was also proposed that monosilyl acetals can be a better alternative to the commonly used dialkyl acetals for the protection of carbonyl compounds. 

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. 

Partial desilylation by means of acetic acid gives the corresponding monosilyl products 7 73 and 7 77 and after subsequent intramolecular hydrosilylation 7,7-dimethyl-7-sila-bicyclo[2,2.1]-heptane (174) and 9,9-dimethyl-9-sila-bicyclol4.2.1]-nonane (178), respectively, can be obtained Adamantanone (179) plus system B (using dichlorodimethylsilane instead of 742) gives rise to 2,2-dimethyl-l,3-dioxa-2-sila-4,5-bis(adamanta)dispiro-cyclopentane (750) ° (see also for the alternative compound with two Me2Si moieties. This reaction is affected via UV irradiation). 

The monosilyl alcohol, prepared as described earlier, is mctalatcd with hexane-free butyl-lithium in diethyl ether in the presence of Af,.V,lV,jV -tetramethylethylenediamine. The soluble dianion is then quenched with trimethylchlorosilane to give, on aqueous sulfuric acid hydrolysis, the alcohol as a 95 5 mixture of ZjE geometrical isomers. This is then converted to the acetate according to standard procedures or to the carbonate with methyl chlorocarbonate. 

Theil et al. developed a method for chemoenzymatic synthesis of both enantiomers of cispentacin [89]. frans-2-Hydroxymethylcyclopentanol, obtained by the sodium borohydride reduction of ethyl 2-oxocyclopentanecarboxylate, was monosilylated with tert-butyldimethylsilyl (TBDMS) chloride to afford 55. Lipase PS-catalysed transesterification with vinyl acetate in /erf-butyl methyl ether furnished the ester 56 and the alcohol 57. The deacetylated 58 was obtained by the Mitsunobu reaction with phthalimide, triphenylphosphine and diethyl azodicarboxylate (DEAD) to furnish the cis oriented 59 with inversion of configuration (not retention as mentioned in the original article) (Scheme 9). Desilylation, Jones oxidation and subsequent deprotection with aqueous methylamine gave the ( R,2S) enantiomer 5 [89]. The (15, 2/f) enantiomer was prepared by the same route from the silyl alcohol 57. 

To 4.24 g (25.8 mmol) of monosilylated diyne 30 in 110 mL of dry THF was added dropwise, under a nitrogen atmosphere, 11 mL (28 mmol) of 2.5 M H-butyUithium in hexane at — 78°C. The mixture was stirred for 30 min, then 7.12 g (30.3 mmol) of p-toluenesulfonyl bromide in 30 mL of THF was added over a 10 min period. The solution was stirred for 30 min at — 78 °C and at room temperature for 1 h. Next, 150 mL of water was added. The layers were separated, and the aqueous layer was extracted with 3 x 50 mL of pentane. The combined extracts were washed with 150 mL each of 10% aqueous sulfuric acid, saturated aqueous sodium bicarbonate, and water, dried over magnesium sulfate, and concentrated under reduced pressure. Column chromatography on silica gel with 10 1 hexane/ethyl acetate gave 4.90 g (76%) of bromoalkyne 50 as a colorless liquid that was 90% pure by GC (contaminants were not characterized). It is not advisable to purify the product by distillation due to the possibility of explosive decomposition - CAUTION [44] ... 

The above kinetically controlled regioselectivity is also reflected in the selective monosilylation of butane-1,2,4-triol. In this case, the sole product obtained is 4-r-butyldimethylsiloxy-butane-l,2-diol with 99% yield (eq 28). The authors rationalized that, with the bulky TBDMSCl, the dibutylstannylene acetal rapidly migrates between the 1,2-diol and 1,3-diols and affords the product of kinetic control. This sequence of reactions was also used to selectively block the equatorial alcohol of a cw-diol on the pyranoside ring... 

The formation of stable iV,0-acetal TMS ethers, which are excellent precursors of V-acyliminium ions, is easily achieved by DIBAL reduction of V-acylamides followed by in situ protection with TMSOTf/pyridine (eq 39). 2,6-Lutidine has also been used as base. The DIBAL reduction-TMSOTf/pyridine silylation sequence has also been applied to the formation of monosilyl... 

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