Asymmetric PTC C-Alkylation Catalyzed by Chiral Derivatives of Tartaric Acid and Aminophenols. Synthesis of (R)- and (S)-α-Methyl Amino Acids

• Published in: Journal of organic chemistry 2000-10, Vol.65 (21), p.7041-7048
• Main Authors: Belokon, Yuri N, Kochetkov, Konstantin A, Churkina, Tatiana D, Ikonnikov, Nikolai S, Chesnokov, Alexey A, Larionov, Oleg V, Singh, Ishwar, Parmar, Virinder S, Vyskočil, Šťepán, Kagan, Henri B
• Format: Article
• Language: English
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo000719p

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 NOBIN's 3a−h) can be used as chiral catalysts in the enantioselective alkylation, as exemplified by the reaction of Schiff's bases 1a−e derived from alanine esters and benzaldehydes with active alkyl halides. Acid-catalyzed hydrolysis of the products formed in the reaction afforded (R)-α-methylphenylalanine, (R)-α-naphthylmethylalanine, and (R)-α-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.