Asymmetric enolate Myers’ alkylation

The utility of chiral oxazoline enolates in asymmetric synthesis has elegantly been demonstrated by Myers (106,120). The stereoselective aldol condensations of these enolates have been examined in a hmited number of cases (eq. [107]) (32,121). Assuming that the enolate formed has the geometry indicated in 164 (120b), the diastereoselection observed for both the aldol condensation and the previously reported alkylations favors electrophile attack on the Re face as indicated. In contrast, the unsubstituted enolate 163b exhibits significantly poorer diastereoface selection with a range of aldehydes (eq. [108]) (121). 

In the laboratory of T.F. Jamison, the synthesis of amphidinolide T1 was accomplished utilizing a catalytic and stereoselective macrocyclization as the key step. ° The Myers asymmetric alkylation was chosen to establish the correct stereochemistry at the C2 position. In the procedure, the alkyl halide was used as the limiting reagent and almost two equivalents of the lithium enolate of the A/-propionyl pseudoephedrine chiral auxiliary was used. The alkylated product was purified by column chromatography and then subjected to basic hydrolysis to remove the chiral auxiliary. 

The Myers asymmetric alkylation is a reaction between the enolate of a pseudoephedrine amide and an alkyl iodide in the presence of lithium chloride to give... 

The preparation of the methyl ketone required for the aldol coupling reaction was accomplished by using the asymmetric alkylation of the unsaturated amide 158 according to a protocol developed by Myers [112]. Asymmetric alkylation of 158 with ethyl iodide gave 159 which was reduced to the primary alcohol (LiNH2, BH3) and protected as a PMB ether to produce, after oxidative cleavage of the olefin, the methyl ketone 160 which was converted to the trimethylsilyl enol ether 161 (LiHMDS, TMSC1) (Scheme 31). 

The work of Myers et al. [6] illustrates the synthetic potential of the use of metal salts (instead of HMPA ) in alkylation reactions of enolates, employing easily accessible amide, enolates of the chiral auxiliary pseudoephed-rine. It is not surprising that the mechanism of chiral induction is not yet fully understood further investigations are necessary. Nonetheless, unanswered questions in enolate chemistry remain even for tailor-made, well-established auxiliaries, whose asymmetric induction can be explained convincingly by working models on monomer enolate structures, considering chelation control and steric factors. 

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