Correlation ester enolates

Similar effects were observed in the structures of the lithium salts of ester enolates [43] studied by Seebach et al. (1985). Here too systematic differences in angles are observed compared with amide and ketone enolates, and there is a correlation between the bond angles and the difference in the two C-O bond lengths at the reaction centre for three compounds [43], consistent with incipient elimination of t-butoxide to give the ketene [44] (Ferretti et al., 1991). 

A further attempt has been made to develop a predictive model for chirality transfer achieved through alkylation reactions of ester enolates which feature chiral auxiliaries. " Hippurate esters (30) derived from (lI , 25 )-trani-2-(p-substituted phenyl)cyclohexanols were found, on reaction with benzyl bromide, to give (31) with predominantly the S configuration at the alkylation centre but with no correlation between the degree of stereoselectivity (20-98%) and the electron density on the aromatic ring. 

Bond Length and Valence Angle Correlations in Ester Enolates... 

The third type of C = CX2 olefin examined from the point of view of structure correlation was the ester enolate. Three crystal structures of lithium ester enolates, obtained in the course of synthetic studies by Seebach et al., provided a total of four fragments depicted in Scheme 6.13 [108]. The variation in the C-O bond lengths and bond angles provides a picture of the incipient stages of elimination of an alkoxy ion (alcoholate OR), yielding a ketene. The C-OR bond length varies between 1.379(3) and 1.412(5) A, and the C = C-0 angle increases from 125.4 to 128.2° (d and / i in Scheme 6.14), i.e. the picture is similar to the enamine one. The other... 

The same stereoselectivity due to a boat-hke transition state has been observed by Lallemand [16] during an approach in the synthesis of antifeedent compound clerodine. Interestingly, a chemical correlation has been done with the products resulting from a Claisen-Ireland rearrangement in the open chain series. Accordingly, the E-ester enolate obtained after deprotonation and silylation of ester 64 [17] afforded, via a chair-like transition state, a compound which was correlated via 63 with the cyclic orthoester product 62 which resulted from a necessarily Z-ketene acetal. Consistently the E-ester enolate gave rise to a diastereomer 65 after the same sequence of reactions (Scheme 6.8). 

A modest direct correlation between the reaction yield and the steric hindrance of the nucleophilic carbon of the starting enolate has been found for conjugate addition of ketone and ester enolates to nitroethene. ... 

The addition of (Z)-3-(alkylamino)-2-butenoic acid esters to nitroalkenes derived from open-chain sugars gave a 50 50 mixture of diastereomeric products 32. The reaction of chiral 2-sub-stituted l-(2-nitroethenyl)pyrrolidines with zinc enolates of 3-substituted tetrahydro-2//-pyran-2-oncs in 1,2-dimethoxyethane at — 78 °C afforded the corresponding 3,3-disubstituted products in 82-96% ee via an addition-elimination process33. The stereochemical course of the reaction was determined by chemical correlation of (S)-( )-3-ethyltetrahydro-3-(2-ni-troethenyl)-2//-pyran-2-one with ( + )-quebrachamine. 

GL 4] [R 5] [P 5] The rate of the fluorination of y0-keto esters is usually correlated with the enol concentration or the rate of enol formation as this species is actually fluorinated [15, 16]. For the fluorination of ethyl 2-chloroacetoacetate in a micro reactor, much higher yields were found as expected from such relationships and as compared with conventional batch processing which has only low conversion. Obviously, the fluorinated metal surface of the micro channel promotes the enol formation. 

In summary, reactions of nitronates with acid anhydrides or acyl chlorides give the O-acylated products, and reactions with acyl imidazoles, phenyl esters, acyl nitriles, and enol-lactones gives the C-acylated products, (see Eq. 5.13).25 The C/O selectivity of nitronate acylation by RCOX is qualitatively correlated with strength (pKJ of the acid HX conjugated to the leaving group X .25... 

Because anti/syn ratios in the product can be correlated to the E(0)/Z(0) ratio of the involved boron enolate mixture,10b initial experiments were aimed at the preparation of highly E(0)-enriched boron enolate. The E(0)/Z(0) ratio increases with the bulk of the alkanethiol moiety, whereas the formation of Z(O) enolates prevails with (S )-aryl thioates. (E/Z = 7 93 for benzenethiol and 5 95 for 2-naphthalene thiol esters). E(O) reagent can be formed almost exclusively by reaction of (5)-3,3-diethyl-3-pentyl propanethioate 64 with the chiral boron triflate. High reactivity toward aldehydes can be retained in spite of the apparent steric demand (Scheme 3-22).43... 

The efficient enantioselective alkylation of the P/y-unsaturated ester 39 was achieved1351 by use of the N-anthracenylmethyl catalyst 12 (R=benzyl, X=Br) together with CsOH-H20 under phase transfer conditions analogous to those in the alkylation of the O Donnell imine 23, as shown in Scheme 13. The enantioselectivity of the alkylation correlates with Hammett o constants, and the N,N-dimethylamino substituents in 39 showed the most effective enantioselectivity. The tight ion pair in which the enolate... 

Although simple alkyl esters (ethyl propionate) fail to enolize with the boryl triflate reagents under normal conditions, the more acidic acyloxyboranes 66 readily form the diboryl enediolates 67 (eq. [52]) (6a,66). Several interesting trends are noted in the data included in Table 23. Since previous studies have demonstrated that enolate geometry strongly correlates with product stereochemistry, enediolate 67 has been employed to directly compare the reactivities... 

The correlation between allylboronic ester stereochemistry and aldehyde diastereoface selection stands in contrast to the behavior of stereochemicaUy defined lithium enolates, which generally exhibit a preference for the Cram mode of addition to chiral aldehydes from either enolate geometry (cf, eqs. [72]-[77]). The stereochemical... 

First, the correlation of ee of the product with the concentration of enol (En) in the original 3-oxocarboxylic ester (MAA) is absent in different solvents the enol content is much different second, it was shown that methyl 2,2-dimethyl-3-oxobutyrate (DMB) (Scheme 5.33.), which cannot form an enol,... 

Also for side chain variations, clear - and in this case quantitative - structure-activity relationships have been established at the target level. In a series of oximino esters of type 4, we obtained a curve (Fig. 13.2.7) in accordance with a bilinear equation [7, 9]. Similar correlations have been deduced for enol ethers, oximino amides, crotonic esters and methoxycarbamates [66]. 

A kinetic study of reactions of 2,3-dichloro-5,6-dicyano-pflra-benzoquinone (140, DDQ) with silyl enol ethers, silyl ketene acetals, allylsilanes, enamino esters and diazomethanes has been carried out in acetonitrile and DCM, allowing correlations with nucleophilicity parameters for the latter species to be examined. These are found to be 2-5 orders of magnitude larger than expected for Single Electron Transfer processes, supporting a polar mechanism for C-C bond formation at C(5). However, rate constants for (9-attack do correlate well with calculated values assuming rate-determining SET. 

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