Elimination keto-ester

The aryl- and heteroarylfluorosilanes 541 can be used for the preparation of the unsymmetrical ketones 542[400], Carbonylation of aryl triflate with the siloxycyclopropane 543 affords the 7-keto ester 545. In this reaction, transme-tallation of the siloxycyclopropane 543 with acylpalladium and ring opening generate Pd homoenolate as an intermediate 544 without undergoing elimination of/3-hydrogen[401],... 

It s reasonable to ask why one would prepare a ketone by way of a keto ester (ethyl acetoacetate, for example) rather than by direct alkylation of the enolate of a ketone. One reason is that the monoalkylation of ketones via their enolates is a difficult reaction to cany out in good yield. (Remember, however, that acylation of ketone enolates as described in Section 21.4 is achieved readily.) A second reason is that the delocalized enolates of (3-keto esters, being far- less basic than ketone enolates, give a higher substitution-elimination ratio when they react with alkyl halides. This can be quite important in those syntheses in which the alkyl halide is expensive or difficult to obtain. 

Another example is the introduction of sulfur functionalities into the keto esters at the a- or a positions, which can be eliminated after the reduction. Methylthiol... 

Unsaturated -Keto Esters, (3-Diketones, and a /3-Keto Sulfoxide Prepared by Selenoxide Elimination... 

The recently reported (757) conversion of 5-pyrazolones directly to a,j8-acetylenic esters by treatment with TTN in methanol appears to be an example of thallation of a heterocyclic enamine the suggested mechanism involves initial electrophilic thallation of the 3-pyrazolin-5-one tautomer of the 5-pyrazolone to give an intermediate organothallium compound which undergoes a subsequent oxidation by a second equivalent of TTN to give a diazacyclopentadienone. Solvolysis by methanol, with concomitant elimination of nitrogen and thallium(I), yields the a,)S-acetylenic ester in excellent (78-95%) yield (Scheme 35). Since 5-pyrazolones may be prepared in quantitative yield by the reaction of /3-keto esters with hydrazine (168), this conversion represents in a formal sense the dehydration of /3-keto esters. In fact, the direct conversion of /3-keto esters to a,jS-acetylenic esters without isolation of the intermediate 5-pyrazolones can be achieved by treatment in methanol solution first with hydrazine and then with TTN. 

Base-promoted fragmentation of products resulting from SRN I reactions between gem-halonitroalkanes and cyclic [1-keto-esters as nucleophiles give rise to di- or trifunctionalized olefins (Eq. 7.141).187 If the product is treated with NaCl in DMSO at 120 °C, the ester and nitro groups are eliminated. 

The trimethylsilyl ethers 212 of four-membered 1-alkenyl-1-cyclobutanols rearrange to the ring-expanded 0-mercuriocyclopentanones 213. These can be converted into the a-methylenecyclopentanones 214 through elimination or further expanded by one-carbon atom into cyclohexanones 215 via the Bu3SnH-mediated free radical chain reactions [116]. A similar radical intermediate is suggested to be involved in the ring expansion of a-bromomethyl-fi-keto esters [117]. (Scheme 84)... 

Reduction of the enolizable keto ester 477 supplied two alcohols, 479 and 480, from both of which the same unsaturated ester 481 could be obtained by easy water elimination. Accordingly, the reduction of 478 yielded alcohols 482, 483, and 484 in addition to 479 and 480 derivable from 477, formed by previous C-18 epimerization of 478. Water elimination of 482 gave 18a-methoxyapoalloyo-himbine (485). By demethylating the three major products 479, 480, and 482, the corresponding C-18-hydroxy derivatives 486, 487, and 488 could be prepared. 

Oxidative radical cyclization of fi-keto esters. Radical cyclizations of unsaturated 0-keto esters initiated by Mn(III) acetate (1) can be terminated by oxidative 0-hydride elimination by Cu(OAc)2 (equation I). This radical reaction can... 

A molecule of CO may also be eliminated from malonates, [132] P-keto esters, [133] phenoxyacetates, [134] and many other compounds containing similar structural features. 

Treatment of the /3-keto ester 220 with sodium ethoxide at elevated temperature triggered off an epoxide ring opening by / -elimination that was followed by the desired Knoevenagel condensation to afford the tricyclic product 206 (Scheme 34). The enone moiety in the intermediate 221 did not show a propensity for deprotonation and, therefore, the ketone carbonyl function of the enone moiety was available for a Knoevenagel condensation. The reduction of the p-keto ester (206) to the corresponding diol was the next objective. Treatment of the TES-protected -keto ester (TES-206) with DIBAH afforded the diastereomeric diols 222 and 223 in a moderate diastereoselec-tivity in favour of the undesired diastereomer 222. The diastereomers were separated and the undesired diastereomer 222 was epimerized to 223 by a sequence that consists of Mitsunobu inversion and benzoate ester reduction [98, 99]. 

Dihydroxy esters of the type 5a can easily be lactonized with concomitant elimination of water to give the corresponding a, 3-unsaturated lactones. Therefore, hydroxy keto ester (R)-2c, obtained by recLBADH-catalyzed reduction of Ic, was reduced with NaBH4 prior to acid-catalyzed lactonization for the synthesis of labdanum fragrance compound (R)-16 (Scheme 2.2.7.8) [12]. 

The decarboxylation of ally / -keto carboxylates generates 7r-allylpalladium enolates. Aldol condensation and Michael addition are typical reactions for metal enolates. Actually Pd enolates undergo intramolecular aldol condensation and Michael addition. When an aldehyde group is present in the allyl ji-keto ester 738, intramolecular aldol condensation takes place yielding the cyclic aldol 739 as a main product[463]. At the same time, the diketone 740 is formed as a minor product by /3-elimination. This is Pd-catalyzed aldol condensation under neutral conditions. The reaction proceeds even in the presence of water, showing that the Pd enolate is not decomposed with water. The spiro-aldol 742 is obtained from 741. Allyl acetates with other EWGs such as allyl malonate, cyanoacetate 743, and sulfonylacetate undergo similar aldol-type cycliza-tions[464]. 

The thermal ring opening of the pyrazoline (351) occurs with elimination of nitrogen and the formation of a keto ester. The latter cyclizes with loss of ethanol to the pyran-2-one (352 Scheme 110) (02CB782). Since pyrazolines may be obtained from a 1,3-dipolar cycloaddition of diazoacetic ester and an unsaturated ketone, this route is in effect a further example of a type (i) synthesis (Scheme 85). 

Bicyclic keto esters can easily be prepared by a process called a,a -annulation.29 Thus, treatment of the enamine of cyclopentanone (64) with ethyl a-(bromomethyl)acrylate (98) affords, after work-up, the bicyclic keto ester (99) in 80% yield (equation IS).2911 The mechanism probably involves an initial Michael addition and elimination (or a simple Sn2 or Sn2 alkylation) followed by an intramolecular Michael addition of the less-substituted enamine on the acrylate unit. The use of the enamine of 4,4-bis(ethoxycarbonyl)cyclohexanone (100 equation 26) with (98) gives a 45% yield of the adaman-tanedione diester (101) (yield based on 100 70% when based on 98) via a,a -annulation followed by Dieckmann condensation.29 Enamines of heterocyclic ketones can also serve as the initial nucleophiles, e.g. (102) and (103) give (105) via (104), formed in situ, in 70% yield (Scheme 11 ).29>... 

In a like manner, vinyl sulfoxides and sulfones can serve as the equivalents of vinyl and alkenyl cations via a process involving a Michael addition followed by an elimination.43 For example, addition of the enolate of the P-keto ester (168 Scheme 24) to phenyl vinyl sulfoxide (169) furnished, in 50% yield. 

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