R-Butyl isobutyrate

Few ester enolate crystal structures have been described. The lack of structural information is no doubt due to the fact that the ester enolates undergo a-elimination reactions at or below room temperature. A good discussion of the temperatures at which lithium ester enolates undergo this elimination is presented in the same paper with the crystal structures of the lithium enolates derived from r-butyl propionate (163), r-butyl isobutyrate (164) and methyl 3,3-dimethylbutanoate (165). It is significant Aat two of the lithium ester enolates derived from (163) and (165) are both obtained with alkene geometry such that the alkyl group is trans to the enolate oxygen. It is also noteworthy that the two TMEDA-solvated enolates from (163) and (164) are dimeric, while the THF-solvated enolate from (165) exists as a tetramer. 

The reagent is prepared from r-butyl isobutyrate and lithium diisopropylamide in hexane at -78°. 

Isobutyl nitrite Butyl alcohol scc-Butyl alcohol t r -Butyl alcohol Ethyl ether Isobutyl alcohol Ethyl sulfide Pyridine Isovaleraldehyde 3-Methyl 2-butanone Isobutyl formate Isopropyl acetate Methyl isobutyrate Isoamyl nitrite tert-Amyl alcohol Isoamyl alcohol... 

Although LHMDS was also used with methyl isobutyrate, better yields were obtained for the same reaction with r-butyl propionate and NaHMDS at room temperature. The a-arylation with t-butyl propionate and LHMDS proceeds only at a higher temperature (80 °C). It was shown later that LiNCy2 could also be very effective for this reaction. More sensitive substrates, such as a-imino esters, required the use of milder base as decomposition was observed with LHMDS. Finally, a-arylation of nitrile derivatives was also reported using LHMDS (eq 24). ... 

In a useful extension of the procedure, f-butyl bromoacetate 310 was used as the substrate and yielded fi-configured a-bromo-P-hydroxy esters 311 in excellent diastereoselectivity and high enantiomeric excess. The adduct to isobutyric aldehyde (311, R = CHMe2) served as an intermediate for obtaining the diastere-omeric (25,35)- and (2R,35)-3-hydroxyisoleucine by replacement of the bromine substituent against the amino group under net retention and inversion, respectively (Scheme 4.69) [152]. 

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