Alkylation of ester enolate

Table 7. Formation of Six-Membered Rings by Intramolecular Alkylation of Ester Enolates...

G. Frater, Alkylation of Ester Enolates , in Stereoselective Synthesis (Houben-Weyl) 4th ed. 1996, (G. Helmchen, R. W. Hoffmann, J. Mulzer, E. Schaumann, Eds.), 1996, Vol. E21 (Workbench Edition), 2, 723-790, Georg Thieme Verlag, Stuttgart. 

The alkylation of enolates constitutes a very powerful method for the formation of C-C bonds. Several methods have been developed in order to control the stereoselectivity of this process. First applications of carbohydrate auxiliaries in stereoselective alkylations of ester enolates were described by Heathcock et al. [152] in 1981. 

When competing Claisen condensation of the ester is a problem, the use of the sterically hindered t-butyl esters is recommended. Unlike with ketone enolates, the 0-alkylation of ester enolates generally is not a problem. Consequently, HMPA may be added to ester enolate alkylations to improve yields. Many S 2 reactions proceed more readily in HMPA than in THF, DME, or DMSO. A solvent for replacing the carcinogenic HMPA in a variety of alkylation reactions is l,3-dimethyl-3,4,5,6-tetrahy-dro-2(lH)pyrimidinone (A,A -dimethylpropyleneurea, DMPU), which also has a strong dipole to facilitate metal counterion coordination. ... 

The formation and further transformation of esters belongs to the fundamentals of organic chemistry. Moreover, some esters have enormous importance for example triglycerides (1), in the form of fats and oils, are produced in million ton quantities for a number of applications. Other esters, e.g. (2) and (3), are olifactory components waxes, e.g. (4), are used commercially to protect metallic surfaces against corrosion. Aspartame (5) is an important artificial sweetener, and pyrethrin (6) is the prototype of the pyre-throids, an unusually potent class of insecticides. Apart from these more applied considerations, esters are important synthetic intermediates in a number of multistep sequences. Striking examples are chain elongations via Homer alkenation or a-alkylations of ester enolates, in particular the ones stereocon-trolled by chiral auxiliaries. ... 

The results of alkylations of ester enolates such as (126) with P-methyl and P-CH20R substituents (which have similar steric requirements) provide additional evidence that alkylation occurs anti to the more strongly electron-releasing P-substituent (Scheme 59). Presumably in (126) a lone pair of electrons on oxygen facilitates electron release by the P-carbon-7-carbon bond. 1110, an alkylation transition state such as (127) may obtain in such cases. Alkylations of dilithium dianions of 3-benzoylaminobutanoic acid esters have also been shown to give mainly the anti 2,3-disubstituted dia-stereomers. ... 

Helmchen and co-workers achieved good asymmetric induction in the alkylation of ester enolates using the camphor based sulfonamide auxiliary in acetate 439.Alkylation of the enolate derived from 439 with iodotetradecane proceeded primarily from the less hindered face (away from the sulfonamide group, to give a 98 2 mixture of 440 and 441. The diastereomer ratio was 98 2 favoring 440 and the yield of 74%. 

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