Lithium enolates of esters

Four different orientations are possible when the enantiofaces of (E)- and (Z)-enolates and an ( )-enone combine via a closed transition state, in which the olefinic moieties of the donor and the acceptor are in a syn arrangement. It should be emphasized that, a further four enan-tiomorphous orientations of A-D are possible leading to the enantiomers 2 and 3. On the basis of extensive studies of Michael additions of the lithium enolates of esters (X = OR) and ketones (X = R) to enones (Y = R) it has been concluded ... 

Closely related to enolate additions to enones is the diastereoselective 1,4-addition of lithium enolates of esters, thioesters and amides to a,/ -unsaturated esters. These reactions provide syn-or ar /-2,3-disubstituted glutarates (pentanedioates). 

Tabic 4. Pentanedioatcs from Addition of the Lithium Enolates of Esters to x./MJnsaturated Esters LiO... 

Various diastereoselective Michael reactions are based on y-bromo-, y-alkyl-, or y-alkoxy-2(5//)-furanones following the trans-face selectivity shown in Section 1.5.2.3.1.2. Thus the lithium enolates of esters such as ethyl propanoate, ethyl a-methoxyacetate and ethyl a-phenylacetate add to methoxy-2(5/f)-furanone with complete face selectivity269-273 (see Section 1.5.2.4.4.2.). 

More traditional carbon nucleophiles can also be used for an alkylative ring-opening strategy, as exemplified by the titanium tetrachloride promoted reaction of trimethylsilyl enol ethers (82) with ethylene oxide, a protocol which provides aldol products (84) in moderate to good yields <00TL763>. While typical lithium enolates of esters and ketones do not react directly with epoxides, aluminum ester enolates (e.g., 86) can be used quite effectively. This methodology is the subject of a recent review <00T1149>. 

Asymmetric hydraxylation of lithium enolates of esters and amides.2 Hydroxylation of typical enolates of esters with ( + )- and (-)-l is effected in 75-90% yield and with 55-85% ee. The reaction with amide enolates with ( + )- and ( — )-l results in the opposite configuration to that obtained with ester enolates and with less enantioselectivity. Steric factors appear to predominate over metal chelation. 

ASYMMETRIC OXIDATION OF LITHIUM ENOLATES OF ESTERS AND AMIDES USING (+)-(2R.8aS)-10-(CAMPHORYLSULFONYL)OXAZIRIDINE... 

Lithium enolates of esters 72 can be made direct from the ester itself with the strong hindered bases LDA or LiHMDS [(Me3Si)2NLi] and react cleanly with even enolisable aldehydes and ketones, e.g. 74, to give aldols 75 in high yield.13... 

Reaction of ester enolates with epoxides.1 Lithium enolates of esters do not open epoxides, but the aluminum enolates do. Li to A1 exchange can be effected with diethylaluminum chloride. The less substituted O-C bond is cleaved and the syn-diastereomer predominates. Reactions of optically active epoxides proceed with high... 

Complete details for synthesis of ( + )- or ( —)-l from (IS)- or (1R)-10-camphor-sulfonic acid in 77% yield are now available. In general, this oxaziridine is less active than other N-sulfonyloxaziridines, but it is the preferred reagent for hydrox-ylation of lithium enolates of esters, amides, and ketones in 30-95% ee.1... 

Zinc enolates, made from the bromoesters, are a good alternative to lithium enolates of esters. The mechanism for zinc enoiate formation should remind you of the formation of a Grignard reagent. 

Nucleophilic dithioacetalisation can be used to introduce acyclic dithioacetals adjacent to carbonyls too. For example the lithium enolate of ester 96.1 was converted to the dithioacetal 96.2 in good yield using methyl methanethiosulfo-nate [Scheme 2.96].191 After elaboration of the chain, the carbonyl group was deprotected by silver(I)-assisted oxidative hydrolysis. 

Oxaziridines. Davis has developed the use of chiral 2-sulfonyloxaziridines derived from camphorsulfonic acid as chiral auxiliaries in the asymmetric oxidation reactions. Although other oxaziridines may be preferable, the camphor-derived oxaziridines can be used for the oxidation of sulfides and disulfides to sulfoxides and thiosulfinates as well as for the epoxidation of alkenes. On the other hand, the camphoryloxaziridines are the preferred reagents for hydroxylation of lithium enolates of esters, amides, and ketones, as utilized in the synthesis of kjellmanianone (eq 17). ... 

Table XX clearly demonstrates that the catalytic function of Al-Mont is far superior to that of homogeneous acid systems. Table XXI shows that a variety of silyl ketene acetals and enoates are applicable to the montmoril-lonite-catalyzed reactions. In particular, successful additions of silyl ketene acetal to ot,p- or, -disubstituted acrylates should be noted because these disubstituted acrylates were reported to be unreactive to lithium enolates of esters (an existent homogeneous method) (79). The Michael addition to enones was also achieved by the use of Al-Mont as shown in Table XXII.

Displacements. Allylic substrates react with lithium enolates of esters, organozincs, and other nucleophiles. The regioselectivities of reactions involving vinyl-... 

Silylation. Lithium enolates of esters and lactones undergo a-silylation with this reagent rather than the more usiial O-silylation encountered with other reagents. Addition of HMPT results in considerable O-silylation. The reagent effects only O-silylation of ketones. 

More impressive and more important is the performance of these lithium enolates in aldol reactions. Ester enolates are awkward things to use in reactions with enolisable aldehydes and ketones because of the very efficient self-condensation of the aldehydes and ketones. The traditional solutions involve such devices as Knoevenagel-style reactions with malonates.11 Lithium enolates of esters, e.g. 76, react cleanly with enolisable aldehydes and ketones to give high yields of aldols,12 e.g. 79 in a single step also involving a six-membered cyclic transition state 77. 

For all their usefulness, enamines have now largely been superseded by silyl enol ethers. These (102-104) can be made directly with Me3SiCl from the lithium enolates of esters or acids or from aldehydes under milder conditions with a tertiary amine. The silicon atom is an excellent electrophile with a strong preference for more electronegative partners and it combines with the oxygen atom of an enolate so rapidly that no self condensation occurs even with aldehydes. 

Lithium enolates of esters are inferior to the zinc enolates with respect to their reactivities towards /3-amino nitroethenes."... 

Conjugate addition. Schlessinger et have reported a general synthesis of 1,4-dicarbonyl compounds based on utilization of (1) as a 2-carbon Michael acceptor. Michael additions were realized with enamines, sodium enolates of /3-dicarbonyl compounds, and lithium enolates of esters. The products can be converted into aldehydes by hydrolysis in aqueous acetonitrile with perchloric acid. 

Lithium enolates of esters containing an a-tertiary carbon atom also undergo this a-hydroxylation reaction. One example of successful oxygenation of an ester with an a-methylene group was reported by Wasserman and Lipshutz. ... 

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