ASYMMETRIC-SYNTHESIS OF ALPHA-AMINO-ACIDS BY COPPER-CATALYZED CONJUGATE ADDITION OF GRIGNARD-REAGENTS TO OPTICALLY-ACTIVE CARBAMATOACRYLATES

Optically active ene carbamates were alpha-lithiated by lithium tetramethylpiperidide in the presence of trialkylstannyl chlorides to produce alpha-stannylated compounds. These underwent facile palladium-catalyzed couplings with acid chlorides to produce alpha-keto ene carbamates in good yield. Treatment of the alpha-stannyl ene carbamates with butyllithium followed by quenching with carbon dioxide and esterification gave optically active carbamatoacrylates. Copper-catalyzed addition of tert-butyl-, 1-naphthyl-, 2-propenyl-, p-methoxyphenyl-, (trimethylsilyl)methyl-, cyclohexyl-, 1-adamantyl-, and isopropyl Grigard reagents followed by quenching at -10 to 25 degrees C and removal of the protecting groups gave the corresponding alpha-amino acids in 70-90% yield and 73-97% ee. Quenching the reaction at low temperature resulted in little if any asymmetric induction.