Asymmetric synthesis of α-methyl-α-amino acids via diastereoselective alkylation of (1S)-(+)-3-carene derived tricyclic iminolactone.

Ta-Jung Lu, Cheng-Kun Lin

Index: J. Org. Chem. 76(6) , 1621-33, (2011)

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Abstract

A novel carene-based alanine-equivalent tricyclic iminolactone 16 has been synthesized via stereoselective dihydroxylation of the double bond, IBX oxidation of the secondary alcohol, esterification of the tertiary alcohol, deprotection of the resulting ester, and subsequent cyclization from commercially available (1S)-(+)-3-carene in 79% overall yield. The iminolactone 16 demonstrated high reactivity toward alkylation with a wide range of electrophiles at room temperature under phase-transfer catalysis conditions. The alkylated products were produced with excellent diastereoselectivities (>98% de) in good isolated yields (86-94%). High yields (83-91%) of optically pure (S)-α-methyl-α-substituted-α-amino acids were obtained by basic hydrolysis of the dialkylated iminolactones with the recovery of the chiral auxiliary 15 (78-87%).