Y-ketoesters

The penicillin-N,S-acetal 479 reacts with N,N-bis(trimethylsilyl)formamide 22c and Hg(OAc)2, apparently via the iminium salt 480, to give the penicillin-N,N-acetal 481 in 65% yield [64]. On treatment of racemic y-ketoesters such as 482 with chiral silylated 1,3-mercaptoalcohols such as 483, in the presence of TMSOTf 20, at room temperature a kinetically controlled 2 1 mixture of the 0,S-acetals... 

One-pot syntheses of 1,4-diketones, y-oxoaldehydes, y-ketoesters, and co-oxoalkanoates have been reported by bond cleavage of cyclic a-nitroketones with KOH in methanol and subsequent Nef reaction (Section 6.1) with KMn04 (Eq. 5.16).31... 

The readily available benzotriazolyl derivative of dimethyl sulfide, compound 821, can be alkylated on a-carbon in a stepwise manner to provide (a,a-disubstituted)alkyl thioethers 823 (Scheme 131). Hydrolysis of these thioethers under mild conditions (5% H2S04 at room temperature) furnishes ketones 824 in high yields. The anion derived from mono substituted (benzotriazol-l-yl)methyl thioether 822 adds to butyl acrylate to give intermediate 826 that can be hydrolyzed to y-ketoester 825. In another example of reactivity of a-(benzotriazol-l-yl)alkyl thioethers, treatment of thioether 822 with BunLi followed by phenyl isocyanate converts it into a-ketoanilide 828, via intermediate adduct 827 <1998JOC2110>. 

The value of 2-acyl-1,3-dithiane 1-oxides in stereocontrolled syntheses has been extended to the enantioselective formation of (3-hydroxy-y-ketoesters through ester enolate aldol reactions <00JOC6027>. 

Reaction of 4a with TiCl4 was carried out in the presence of siloxyalkene 3 as nucleophile and the results are summarized in Table III. In the reaction with ketene silyl acetals 3a and 3e at -78 °C, y-ketoesters 15a and 15e were obtained instead of chloride product 8 which is a major product in the absence of 3. Formation of product 15 is likely to result from trapping of alkylideneallyl cation 5 with 3 at the sp2 carbon. In contrast, the reactions with silyl enol ethers 3f and 3g gave no acyclic product 15, but gave cyclopentanone derivatives 16-18. The product distribution depends on the mode of addition of TiCl4 (entries 4-7). 

Y-KETOESTERS from aldehydes via DIETHYL ACYLSUCCINATES 4-OXOHEXANOIC ACID ETHYL ESTER... 

FROM a,a -DIBROMOKETONES AND ENAMINES 2,5-DI-METHYL-3-PHENYL-2-C Y CLOPENTEN-1 -ONE y-KETO-ESTER TO PREPARE CYCLIC DIKETONES 2-METHYL-1,3-CYCLOPENTANEDIONE, with the companion preparation y-KETOESTERS FROM ALDEHYDES VIA DIETHYL ARYLSUCCINATES 4-OXOHEXANOIC ACID ETHYL ESTER, which gives the procedure used to prepare the needed... 

The hydroesterification of dienes gave both the unsaturated monoesters and saturated diesters.524 In some cases, y-ketoesters were obtained and carbonylation of 1,5-cyclooctadiene in absence of alcohol gave a ketone.525 [PdI2(PBu3)2] was used as catalyst. If the catalyst contained a halide anion, butadiene underwent normal hydroesterification. When halide-free catalysts were used, the reaction took a different course. Dimerization of the diene occurred to give the ester of 3,8-nonadienoic acid as the major product (equation 128).526-528... 

Schlessinger has shown that the addition of ester enolates to sulfur stabilized acceptors, e.g. ketene di-thioacetal monoxide (151) and methyl a-(methylthio)acrylate (187), is highly efficient for the synthesis of Y-ketoesters.148 Similarly, Ahlbrecht and Seebach have reported that amide and ester enolate additions to nitrogen stabilized acceptors, e.g. nitroalkenes (40) and 2-(/V-methylanilino)acrylonitrile (59 Scheme 72), are highly efficient.149... 

With R2 = OEt, however, some condensation to the furan derivative 103 cannot be avoided. Homologisation of ethyl benzoylacetate via the silyl compound 100 with diazomethane to the y-ketoester 102 is incomplete, and hydrolyzed starting material is recovered. 

Siloxycyclopropanes are quantitatively converted into )5-acetoxymercuriketones by reaction with mercuric acetate. Successive treatment with PdCl2 or PdCl2 + CO gives a-methyleneketones or y-ketoesters, respectively. The ring cleavage takes place highly selectively at the least substituted cyclopropane carbon atom (equation 60) . 

The formation of 4-hydroxycycloheptanones (in the form of bicyclic lactols) is a two-step process, the second step involving intramolecular reaction of Y-(3-halopropyl)-y-butyrolactones which is photoassisted. An alternative route to the same products is initiated by C-alkylation of the ketyls derived from y-ketoesters. Properly constituted ketonitriles are converted to a-ketols via a C-C bond formation process. 

In the presence of CuCN, these homoenolates react with acid chlorides to make y-ketoesters but their forte is reaction with allylic phosphates. Prenyl diethylphosphate gives 45 in good yield and the more highly substituted product 46 is formed in near quantitative yield. These are impressive results both reagents react through the y-carbon the homoenolate 43 where the Zr is and the allylic phosphate where the phosphate isn t. 

Chiral Ru complexes are successful in reducing even y-ketoesters, producing... 

JR)- and (S)-binaphthols 1.44 [230-235] have sometimes been used as chiral auxiliaries. Examples include reduction of y-ketoester 1.45 [236], nucleophilic substitution of binaphthol ethers (G = binaphthol) 1.46, by organomagnesium reagents, organocuprate additions to binaphthol monodnnamates [237], and alkylations of arylacetic or crotonic esters [238,239]. 

Y-KETOESTERS TO PREPARE CYCLIC DIKETONES 2-METHYL-1,3-CYCLOPENTANEDIONE... 

While only 1.0 equiv. of PMHS is needed to complete the reduction of some ketones e. g. a,a,a-trifluoroacetophenone (Ic) and methyl phenylglyoxylate (Id), excess PMHS is necessary in most cases. As shown in Table 1, inconplete conversions are mostly observed for the reduction of relatively acidic substrates i. e. y ketoesters If and Ig and /0-ketoamides Ih and li (pKa = 10-13). Therefore, a likely hypothesis is that the [Zn-diamine]/PMHS system is active not only for the reductive reaction of the carbonyl function, but also for the oxidative silylation of any enolisable group. Thus, the enol-silyl ether produced would hydrolyze back in methanol to the free enol, accounting for the consumption of extra equiv. of PMHS. Nevertheless, this hypothesis does not accotmt for the reduction of imine 3a, since no inqirovement in the conversion is noted on doubling the amount of PMHS (Scheme 3, Table 1). Other imines e. g. 3b, are readily reducible with the present Zn-diamine-methanol system. 

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