Asymmetric PTC C-alkylation catalyzed by chiral derivatives of tartaric acid and aminophenols.: Synthesis of (R)- and (S)-α-methyl amino acids

A new type of efficient chiral catalyst has been elaborated for asymmetric C-alkylation of CH acids under PTC conditions. Sodium alkoxides formed from chiral derivatives of tartaric acid and aminophenols (TADDOL's 2a-e and NOBLN's 3a-h) can be used as chiral catalysts in the enantioselective alkylation, as exemplified by the reaction of Schiff's bases Pa-e derived from alanine esters and benzaldehydes with active alkyl halides. Acid-catalyzed hydrolysis of the products formed in the reaction afforded (R)-alpha -methylphenylalanine, (R)-alpha -naphthylmethylalanine, and (R)alpha -allylalanine in 61-93% yields and with ee 69-93%. The procedure could be successfully scaled up to 6 g of substrate 1b. When (S,S)-TADDOL or (R)-NOBIN are used, the (S)-amino acids are formed. A mechanism rationalizing the observed features of the reaction has been suggested.