Ketene 5,5-acetals hydrolysis

The oxidation of the cyclic enol ether 93 in MeOH affords the methyl ester 95 by hydrolysis of the ketene acetal 94 formed initially by regioselective attack of the methoxy group at the anomeric carbon, rather than the a-alkoxy ketone[35]. Similarly, the double bond of the furan part in khellin (96) is converted ino the ester 98 via the ketene acetal 97[l23],... 

Acetylsultam 15 is also used for stereoselective syntheses of a-unsubstituted /1-hydroxy-carboxylic acids. Thus, conversion of 15 into the silyl-A/O-ketene acetal 16 and subsequent titanium(IV) chloride mediated addition to aldehydes lead to the predominant formation of the diastereomers 17. After separation of the minor diastereomer by flash chromatography, alkaline hydrolysis delivers /f-hydroxycarboxylic acids 18, with liberation of the chiral auxiliary reagent 1919. 

However, in subsequent work it was found that carboxylic acid groups readily add to ketene acetals to form carboxyortho ester linkages (24). These are very labile linkages and on hydrolysis regenerate the carboxylic acid group which then exerts its catalytic function. Because carboxylic acids add so readily to ketene acetals, very labile polymers can be prepared by the addition of diacids to diketene acetals. The utilization of such polymers is currently under investigation. 

The trimethylsilyl ester of a-trimethylsilyacetic acid 1613 is converted by LDA and TCS 14 into the C,0,0-tris(trimethylsilyl)ketene acetal 1614 in 91% yield. Reaction of 1614 with benzaldehyde in the presence of ZnBr2 proceeds via 1615 to afford a high yield of trimethylsilyl cinnamate 1616 [18], which gives on work-up free ( )-cinnamic acid in nearly quantitative yield (Scheme 10.7). In contrast, reaction of the lithium salt of 1613 with benzaldehyde then acidic hydrolysis affords a 1 1 mixture of ( )- and (Z)-cinnamic acid in 86% yield [18]. 

The use of oxygen-containing dienophiles such as enol ethers, silyl enol ethers, or ketene acetals has received considerable attention. Yoshikoshi and coworkers have developed the simple addition of silyl enol ethers to nitroalkenes. Many Lewis acids are effective in promoting the reaction, and the products are converted into 1,4-dicarbonyl compounds after hydrolysis of the adducts (see Section 4.1.3 Michael addition).156 The trimethylsilyl enol ether of cyclohexanone reacts with nitrostyrenes in the presence of titanium dichloride diisopropoxide [Ti(Oi-Pr)2Cl2], as shown in Eq. 8.99.157 Endo approach (with respect to the carbocyclic ring) is favored in the presence of Ti(Oi-Pr)2Cl2. Titanium tetrachloride affords the nitronates nonselectively. 

The first synthesis of a cyclopropenone was reported in 1959 by Breslowls who achieved the preparation of diphenyl cyclopropenone (11) by reacting phenyl ketene dimethylacetal with benzal chloride/K-tert.-butoxide. The phenyl chloro carbene primarily generated adds to the electron-rich ketene acetal double bond to form the chlorocyclopropanone ketal 9, which undergoes 0-elimination of HC1 to diphenyl cyclopropenone ketal 10. Final hydrolysis yields 11 as a well-defined compound which is stable up to the melting point (120—121 °C). 

Although there are other unsaturated compounds that will undergo addition-elimination with free radicals, the benzyl ketene acetal XIV appears to be the most active double bond as far as rate of addition is concerned and the most efficient as far as regards to the extent of elimination is concerned. A comparison with the list of chain transfer agents listed in the Polymer Handbook (23) indicated that only the sulfur compounds appear to be more effective than XIV. Hydrolysis of the end-capped oligomer gives a macromer that is terminated with a carboxylic acid group. 

The formation of orthoester may be explained tiy the preferential addition of tlie ketene acetal to the most reactive alcohol function (primary hydroxyl g,roup) giving thc f non - i so 1 a t ed) acyclic orthoester whicti is attacked by the neighbouring OH-4 with subsequent elimination of methanol. The partial hydrolysis of the diacetate is assumed to proceed through protonation of the methoxyl group (7), via the dioxocarbenium ion 8 and the orthoacid 9. collapse of 9 by either [lath b or path a accor-ding to the mechanism generally proposed (see, for instance, ref. 29 and refs. cited therein) affords the compounds 5 or respectively. 

The structure of the a-methylenecyclopropanone ketal 185 is reminiscent of the addition mode of the corresponding TMM to C=0 [196]. The ester 186 is probably the product of silica-gel-catalyzed hydrolysis of the ketene acetal 187 (Figure 4.8), which is the expected product in the reaction ofTMM with electron-deficient olefins [197]. At higher temperatures 185 isomerizes into 187 [195], NMR spectroscopic investigations of these adducts reveal that the cycloadditions occur at the [6,6] double bonds. Analogous products to 185-187 have been observed for the reaction of the... 

N-Acylation of 2-methyl-5,6-dihydro-4/f-l,3-thiazine with cinnamoyl chloride in the presence of triethylamine furnishes ( )-l-(2-methylenetetrahydro-l,3-thiazin-3-yl)-3-arylprop-2-en-l-ones 122. These products undergo hydrolysis readily due to the j jA -ketene acetal-type bonds present in the molecules and are therefore not stable. Thus ( )-3-(3-(4-methoxyphenyl)acrylamido)propyl ethanethioate 123 is isolated in 92% yield from the corresponding thiazine after column chromatography on Si02 or AI2O3 <2001S135>. 

Cumulenes such as butatrienes and hexapentaenes can undergo cycloaddition at several possible double-bond sites. The electrophilic l,l-diphenyl-4,4-bis(trifluoromethy )butatriene (34), however, reacts with ketene acetals and geminal enediamines at the central double bond exclusively.25 In the case of the ketene acetal cycloadduct 35 (R1 = H R2 = R3 = OMe). acid-catalyzed hydrolysis gives the cyclobutanone. 

In contrast to titanium(IV) tetrachloride, which causes polymerization of a,3-unsaturated esters, aluminum triflate88 or aluminum-impregnated montmorillonite87b are excellent promoters of silyl ketene acetal additions to a,(3-unsaturated esters (Scheme 35). Similarly, the addition of silyl ketene acetals and enol silyl ethers to nitroalkenes, followed by Nef-type work-up, affords y-keto esters (216) and y-di-ketones (218), respectively (Scheme 35).89a>89b Mechanistically, the y-diketones (218) arise from Nef-type hydrolysis of an initial nitronate ester (217).89e 89d Mukaiyama reports that SbCls-Sn(OTf)2 catalyzes diastereoselective anti additions of silyl ketene acetals, silyl thioketene acetals and enol silyl ethers to a,(3-unsaturated thioesters (219).90... 

Mukaiyama-Michael addition of a chiral ketene acetal to nonprochiral vinyl ketones gives products of 72-75% ee.145 A chirally modified glycine derivative (Schiff-base) adds to vinylic phosphorus compounds to yield, after hydrolysis, products with 54-85% ee.146 Another chiral glycine equivalent was used for the preparation of homochiral proline derivatives via diastereoselective addition to a,3-unsatu-rated aldehydes and ketones.147-148... 

Asymmetric 1,3-dipolar cycloaddition of nitrones to ketene acetals is effectively catalyzed by chiral oxazaborolidines derived from N-tosyl-L-a-amino acids to afford 5,5-dialkoxyisoxa-zolidines with high regio- and stereoselectivity [70] (Eq. 8A.46). Hydrolysis of the N-O bond of the resulting chiral adducts under mild conditions yields the corresponding [1-amino esters quantitatively. 

In a maimer exactly analogous to the a-hydroxylation of ketone silyl enol ethers (Sections 2.3.2.1.3.i and 2.3.2.2.3.i) the corresponding ester silyl ketene acetals may be epoxidized by poacid and subsequently cleaved with fluoride to reveal the a-hydroxy ester.Yiel are good if hexanes are employed as solvent, while competing hydrolysis hampers the process in other media. The equivalent lactone hydroxylations are, however, not possible since hydrolysis is the dominant process even in hexane. This solvent limitation may prove restrictive to the widespread use of this technique. 

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. 

Thietanone 1,1-dioxide ketals and 3-aminothiete 1,1-dioxides are readily available by cycloaddition of sulfenes to ketene acetals and enamines, respectively (Section V.3.B.). Hydrolysis of these ketals " and the aminothiete sulfones (which are enamines) " " gives 3-thietanone 1,1-dioxides in fair to good yields, as exemplified by the hydrolysis of 133 and 402. Aqueous mineral acids or acidic ion-exchange resins catalyze the reaction. Cis-2-chloro-2,4,4-trimethyl-3-morpholinothietane 1,1-dioxide reacts with N sodium hydroxide to give 38% 2,2,4-trimethyl-3-thietanone 1,1-dioxide, but the trans isomer is recovered unchanged. 3-Methoxy- and 3-ethoxythiete 1,1-dioxide (enol ethers) are also hydrolyzed to 3-thietanone 1,1-dioxide. In several cases, the hydrolysis products are written as enols of the 3-thietanone sulfone. ... 

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