Esters, 4-hydroxy dianions

A careful study of the alkylation of several enolates of dialkyl malate esters has been reported.74 These esters form dianions resulting from deprotonation of the hydroxy... 

Taylor, E.C., and Davies, H.M.L., Rhodium(II) acetate-catalyzed reaction of ethyl 2-diazo-3-oxopent-4-enoates. Simple routes to 4-aryl-2-hydroxy-l-naphthoates and P,y-iinsaliiralcd esters. The dianion of ethyl 4-(diethylphosphono)acetoacetate as a propionate homoenolate equivalent, Tetrahedron Lett., 24, 5453. 1983. 

For the mechanistic course of the reaction the diketone 5 is assumed to be an intermediate, since small amounts of 5 can sometimes be isolated as a minor product. It is likely that the sodium initially reacts with the ester 1 to give the radical anion species 3, which can dimerize to the dianion 4. By release of two alkoxides R 0 the diketone 5 is formed. Further reaction with sodium leads to the dianion 6, which yields the a-hydroxy ketone 2 upon aqueous workup ... 

Scheme 65 summarizes Mori s synthesis of 44 [97]. Reduction of keto ester A with baker s yeast gave hydroxy ester B of about 98% ee. Methylation of the dianion derived from B diastereoselectively gave C, which was converted to 44. This process enabled the preparation of about 10 g of (lS,5R)-44. 

Alternatively, the ant1-a-alky1-g-hydroxy ester structure may be obtained by alkylation of the dianion of a 6-hydroxy ester, which occurs with 95%... 

When the lithium dianion was prepared in a completely different manner, viz from an a,j -epoxy ester 8 by treatment of the latter with lithium in liquid ammonia and tetrahydrofuran at - 78 C, alkylation experiments (CH3I, — 40 °C) gave the expected a-alkyl- -hydroxy ester 10, but in a ratio of only 4 1 in favor of the anti-isomer and not in the usual 19 1 ratio15. This result could be interpreted as a direct consequence of the participation of an intermolecularly chelated dianionic enolate such as 7 which gains importance because of the use of ammonia as a cosolvent. 

It can be seen from the table that the diastereoselectivities are in the range of 80-99%. Attack of the electrophile is at the opposite face to the amino group furnishing the a/th-product 3, i.e., the alkylation has the same steric course as has been observed for the dianions of /(-hydroxy esters (see Section 1.1.1.3.2.1.1.1.2.). 

Good yields and high to excellent diastereoselectivities have been realized by the dianion alkylation of cyclic /1-hydroxy esters (see Table 5). Because of the cyclic structures these results correspond to the creation of quaternary carbon centers. 

The most important esters in connection with Li batteries are y-butyrolactone (BL) and methyl formate (MF). Li is apparently stable in both solvents due to passivation. Electrolysis of BL on noble metal electrodes produces a cyclic 0-keto ester anion which is a product of a nucleophilic reaction between a y-butyrolactone anion (produced by deprotonation in position a to the carbonyl) and another y-BL molecule. FTIR spectra measured from Li electrodes stored in y-BL indicate the formation of two major surface species the Li butyrate and the dilithium cyclic P-keto ester dianion. The identification of these products and related experimental work is described in detail in Refs. 150 and 189. Scheme 3 shows the reduction patterns of y-BL on lithium surfaces (also see product distribution in Table 3). In the presence of water, the LiOH formed on the Li surfaces due to H20 reduction attacks the y-BL nucleophilically to form derivatives of y-hydroxy butyrate as the major surface species [18] [e.g., LiO(CH2COOLi)]. We have evidence that y-BL may be nucleophilically attacked by surface Li20, thus forming LiO(CH2)3COOLi, which substitutes for part of the surface Li oxide [18]. MF is reduced on Li surfaces to form Li formate as the major surface species [4], LiOCH3, which is also an expected reduction product of MF on Li, was not detected as a major component in the surface films formed on Li surfaces in MF solutions [4], The reduction paths of MF on Li and their product analysis are presented in Scheme 3 and Table 3. 

The asymmetric hydroxylation of ester enolates with N-sulfonyloxaziridines has been less fully studied. Stereoselectivities are generally modest and less is known about the factors influencing the molecular recognition. For example, (/J)-methyl 2-hydroxy-3-phenylpropionate (10) is prepared in 85.5% ee by oxidizing the lithium enolate of methyl 3-phenylpropionate with (+)-( ) in the presence of HMPA (eq 13). Like esters, the hydroxylation of prochiral amide enolates with N-sulfonyloxaziridines affords the corresponding enantiomerically enriched a-hydroxy amides. Thus treatment of amide (11) with LDA followed by addition of (+)-( ) produces a-hydroxy amide (12) in 60% ee (eq 14). Improved stereoselectivities were achieved using double stereodifferentiation, e.g., the asymmetric oxidation of a chiral enolate. For example, oxidation of the lithium enolate of (13) with (—)-(1) (the matched pair) affords the a-hydroxy amide in 88-91% de (eq 15). (+)-(Camphorsulfonyl)oxaziridine (1) mediated hydroxylation of the enolate dianion of (/J)-(14) at —100 to —78 °C in the presence of 1.6 equiv of LiCl gave an 86 14 mixture of syn/anti-(15) (eq 16). The syn product is an intermediate for the C-13 side chain of taxol. 

P-Hydroxy esters may be alkylated via their dilithium dianions. Deprotonation of the hydroxy group by the base prevents its elimination to form an a,P-unsaturated system. Two recent publications by Prater et alP and by Seebach et al ° provide summaries of the results of the alkylations of nonracemic... 

A water soluble activated ester of methoprene (Figure 5, Structure 16) was also prepared from sodium l-hydroxy-2-nitro-4-benzene sulfonate (16). The amount of compund 16 in crude preparations which contained both compound 16 and the free dianion (Figure 5, Structure 17) was determined by spectrophotometry in aqueous solution. Upon hydrolysis compound 16 yielded the dianion (Structure 17) which absorbed visible light at 406 nm in the presence of nucleophiles (Figure 5). Two absorbance readings were required to determine the amount of compound 16 present in the crude material. 

Alkylation of fahydroxy carboxylic esters (8, 258). Dianions of / -hydroxy carboxylic esters (LDA, —50° to —20°) are alkylated stereoselectively to give mainly f/irao-compounds (equation I). The alkylation of dianions of a-mono-... 

The hydroxy ester (S)-B (92% ee) was converted to iodide (S)-C (4 steps). Inversion of the configuration of (S)-B to (-R)-D was possible by means of Mitsunobu inversion, which was further converted to (R)-C. Accordingly, both the enantiomers of C were prepared from the single enantiomer (S)-B. Alkylation of the dianion of methyl acetoacetate with (S)-C gave E, whose further alkylation with (S)-C afforded F. Successive treatments of F with base followed by acid effected hydrolysis, decarboxylation and acetaliza-tion to give (2S,6R,8S)-88 as a volatile oil. Similarly, (R)-C afforded (2R,6S,8R)-88. Both 88 and 88 were purified by chromatography and distillation, and they showed [a]o23 -51.6 (pentane) and +51.7 (pentane), respectively. 

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