New synthetic reactions of enolates of [alpha]-amino acid derivatives

Abstract

Hydroxyalkylation and acylation reactions of lithium enolates of amino acid derivatives 11-13 were investigated. Extensive rearrangement of 11 occurred under the reaction conditions. The lithium enolate of 12 exhibited little or no reaction with benzaldehyde or propionyl chloride and 12 failed to survive the vigorous acidic conditions required to remove the nitrogen protecting group. The dilithium dianion of 13 smoothly underwent hydroxyalkylation with aliphatic, α,β-unsaturated, and aromatic aldehydes at -78°C to give two diastereomers in approximately equal amounts. The dilithium dianion of 13 did not add to cyclohexanone at -78 °C but did react at -25 °C. The hydroxyalkylation reaction was insensitive to the amide base used to generate the dilithium dianion of 13. The acylation reaction of the dilithium dianion of 13 occurred in moderate to good yield at -78 °C. The amide base employed had a significant effect on the success of the reaction. The acylation reaction appeared to be general for aliphatic acid chlorides. Aryl acid chlorides exhibited a dependency on the concentration of the dilithium dianion of 13.