Asymmetric Alkylations of Glycine Derivatives Using Optically Active Formylcamphors

Abstract

3-(Hydroxymethylene)camphor, the enol of 3-formylcamphor, was allowed to react with ethyl glycinate to give aminomethylene compound. The alkylations of the compound with methyl iodide and benzyl chloride in the presence of LDA afforded L-amino acids in low asymmetric yields such as Ala (9.2% e. e.) and Phe (4.3% e. e.), respectively.
On the other hand, D-N-methylalanine (43.3 % e. e.) and D-N-me thylphenylalanine (26.5% e. e.) were obtained by the same alkylations when ethyl N-methylglycinate was used instead of ethyl glycinate. Thus pronounced effect of N-substituent of glycine was observed.
exo-3-Formyl-3-methylcamphor was prepared and allowed to react with ethyl glycinate to give Schiff base. The Schiff base would be expected to activate the methylene group of glycine moiety and to increase the enantioselectivity by 3-methyl group of camphor moiety. The alkylations of the Schiff base with methyl iodide, benzyl chloride and isobutyl iodide gave L-Ala (70.2% e. e.), D-Phe (84.7% e. e.) and L-Leu (71.6% e. e.), respectively. And the alkylations with sec. alkyl halides were also examined.