Enolates chelation effects

Similar chelation effects are present in a-alkoxymethyl derivatives. Magnesium enolates give predominantly the Z-enolate as a result of this chelation. The corresponding trimethylsilyl ketene acetals give E,Z mixtures.248... 

The /3-ketoesters [RC(0 ) CIIC(0)0R] are close analogs which also chelate effectively. A useful general method for synthesis of Co11 compounds of these molecules has been reported, which uses the lithium, caesium, or trimethylsilyl enolate of the /3-ketoester reacting with a Co11 salt in tetrahydrofuran.427... 

The carbocupration of methoxyallene affords a (Z)- or (E)-enol ether depending on the solvent used [52], In THF, the reaction exhibits Z-selectivity because the coordination ability of THF excludes the intramolecular chelation effect of the methoxy group, which may be responsible for the E-selectivity for the reaction in ether (Scheme 10.49). 

In 1978, Larcheveque and coworkers reported modest yields and diastereoselectivities in alkylations of enolates of (-)-ephedrine amides. However, two years later, Evans and Takacs and Sonnet and Heath reported simultaneously that amides derived from (S)-prolinol were much more suitable substrates for such reactions. Deprotonations of these amides with LDA in the THF gave (Z)-enolates (due to allylic strain that would be associated with ( )-enolate formation) and the stereochemical outcome of the alkylation step was rationalized by assuming that the reagent approached preferentially from the less-hindered Jt-face of a chelated species such as (133 Scheme 62). When the hydroxy group of the starting prolinol amide was protected by conversion into various ether derivatives, alkylations of the corresponding lithium enolates were re-face selective. Apparently, in these cases steric factors rather than chelation effects controlled the stereoselectivity of the alkylation. It is of interest to note that enolates such as (133) are attached primarily from the 5/-face by terminal epoxides. ... 

More recently Katsuki and coworkers have reported that (Z)-enolates of a-alkyl and a-heterosub-stituted amides such as (134), derived from pyrrolidine derivatives having a C2 axis of symmetry, undergo very diastereoselective alkylations with secondary alkyl and other alkylating agents in good to excellent chemical yields (Scheme 62) As with prolinol ether amide enolates, it appears that the direction of approach of the alkylating agent to the enolate (134) is controlled mainly by steric factors within the chiral auxiliary, i.e. chelation effects seem to be of little importance. 

Excellent, high diastereoselective control can be achieved with organotin derivatives using potassium hexamethyldisilazanide for deprotonation. As a consequence of the defined enolate geometry by chelation effects, the (/T)-cstcr gives syn-23 as the main product (syn/anti ratio 39 1), whereas the (Z)-esler leads to anti-23 (antijsyn ratio > 40 1)50°. 

These and other related enolate ratios are interpreted in terms of a tight, reactantlike TS with Li chelation in THE and a looser TS in the presence of HMPA. The chelated TS favors the E-enolate, whereas the open TS favors the Z-enolate. The effect of the HMPA is to solvate the Li+ ion, reducing the importance of Li+ coordination with the carbonyl oxygen. ... 

The coupling of 96 with 77 was followed by the epoxidation to give 98. Aldol reaction of lithium enolate of ethyl acetate was conducted by the remote chelation effect with the C7-oxygen atom as well as by a steric bulkiness of the Cg-methyl group at the transition state. As a result of this unexpected bonus, the product 99 was stereochemically pure at the C3 position. The operation to... 

Chelation effects in general override the usual preferences in the formation of lithium ester enolates, and the (Z)-configured enolates are obtained nearly exclusively. Therefore the stereochemical outcome of the rearrangement should only be controlled by the olefin geometry in the allyl moiety and by the transition state (chair vs. boat). If substituted allyUc esters of glycolic add or related a-hydroxy-acids are subjected to rearrangement, synthetically valuable unsaturated a-hydroxyadds are obtained, albeit the yield and stereoselectivity strongly depends on the substrate and the reaction conditions used. 

The relative and absolute configuration of the products was determined by X-ray crystallography. The stereochemical outcome of the rearrangement was in accordance with previous results and presumed to be due to the Li-chelation effect seen in intermediate 114, which results in a sterically biased attack on the less hindered J c-face of the enolate double bond and a chair-like transition state during the Car-roll rearrangement (Scheme 8.39). 

One can infer from this mechanism that a chelating effect (fig. 6) governs the key intermediate this is similar to the mechanism later applied to cerium(IIl)-assisted reductions, and is also closely related to the intermediate proposed as part of the first example of a cross-aldol reaction of cerium enolates (section 4.4). 

It is known that silicon with bulky substituents can serve as an efficient stereo-directing functional element. In addition, silicon is a synthetic equivalent for an aUcoxy substituent, which opens a straightforward approach to the stereocontroUed aldol addition of acyclic molecules (Scheme 3.65). The protocol by Fleming ti al. starts with 1,4-addition of a silylcuprate to enoate 325 to give enolate (Z)-326 selectively under kinetic control, probably due to a chelating effect of the metals. On re-protonation and subsequent deprotonation with LDA, the enolate... 

Trimethylsilyloxyfuran 338 has shown promise as a masked butenolide fragment To fuUy exploit these qualities, the threo versus erythro (339 vs 340) diastereoselectivity in aldol-type additions has to be controlled. In fact it has been shown that this is easily achieved by appropriate reaction conditions. Applying Mukaiyama conditions (i.e., using the silyl enol ether as the donor in the presence of a Lewis acid such as TESOTf to generate oxonium species) leads to threo preference for 339, presumably via an open transition state, whereas desilylation with TBAF generates the erythro-diastereomer 340, this time via a closed Diels-Alder (or Zimmerman-Traxler)-like transition state. In both cases, chelating effects can be ruled out... 

Deprotonation of enols of P-diketones, not considered unusual at moderate pH because of their acidity, is faciUtated at lower pH by chelate formation. Chelation can lead to the dissociation of a proton from as weak an acid as an aUphatic amino alcohol in aqueous alkaU. Coordination of the O atom of triethanolamine to Fe(III) is an example of this effect and results in the sequestration of iron in 1 to 18% sodium hydroxide solution (Fig. 7). Even more striking is the loss of a proton from the amino group of a gold chelate of ethylenediamine in aqueous solution (17). 

The effect of chelating polyamines on the rate and yield of benzylation of the lithium enolate of 1-tetralone was compared with HMPA and DMPU. The triamine... 

In the discussion of the stereochemistry of aldol and Mukaiyama reactions, the most important factors in determining the syn or anti diastereoselectivity were identified as the nature of the TS (cyclic, open, or chelated) and the configuration (E or Z) of the enolate. If either the aldehyde or enolate is chiral, an additional factor enters the picture. The aldehyde or enolate then has two nonidentical faces and the stereochemical outcome will depend on facial selectivity. In principle, this applies to any stereocenter in the molecule, but the strongest and most studied effects are those of a- and (3-substituents. If the aldehyde is chiral, particularly when the stereogenic center is adjacent to the carbonyl group, the competition between the two diastereotopic faces of the carbonyl group determines the stereochemical outcome of the reaction. 

An indication of the relative effectiveness of oxygen substituent in promoting chelation of lithium enolates is found in the enolates 3a-d. The order of preference for the chelation-controlled product is CH30CH20 > TMSO > PhCH20 > TBDMSO, with the nonchelation product favored for TBDMSO.107... 

In summary, the same factors that operate in the electrophile, namely steric, chelation, and polar effects, govern facial selectivity for enolates. The choice of the Lewis acid can determine if the enolate reacts via a chelate. The final outcome depends upon the relative importance of these factors within the particular TS. 

Use of the above conditions in conjunction with the enol tosylate 32, provided only low yields of 22, prompting an extensive screening of structurally diverse phosphine ligands/solvents and palladium sources to attempt to define suitable conditions. Quite quickly a number of conditions were found to be effective, with chelating diphosphines being superior to monodentate phosphines (Table 9.7). In... 

Thus, the postulated chelated enolates and their alkylation reaction make the intra-annular chirality transformation possible. This method for enolate formation is the focal point of this chapter, as this is by far the most effective approach to alkylation or other asymmetric synthesis involving carbonyl are compounds. 

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