Asymmetric Synthesis of α,α-Disubstituted α-Amino Acids by Diastereoselective Alkylation of Camphor-Based Tricyclic Iminolactone

A novel and convenient route for the preparation of chiral tricyclic iminolactones 9 and 10 from camphorquinone has been developed. Alkylation of iminolactones 9 and 10 provided iminolactones 16 and 17 in high yields which were, in turn, alkylated again to afford the α,α-disubstituted products in good yields (70−90%) and excellent diastereoselectivities (>98%). Hydrolysis of the alkylated iminolactones furnished the desired α,α-disubstituted α-amino acids in good yields and high enantiomeric excesses with good recovery yields of the chiral auxiliary 12 and 13. The extremely high endo-face selectivity for alkylation is discussed using semiempirical (MOPAC 93) calculations.