Stereochemical Studies. XLIV. Exploitation of the New Synthetic Scheme for Chiral Additives Usable in Asymmetric Syntheses. Novel Syntheses of optically Active γ-Amino Acids and Pyrrolidines from L-α-Amino Acids

摘要: Aiming to prepare optically active pyrrolidines (2) which are usable as chiral additives for asymmetric syntheses via enamines, and whose absolute configurations can correspond that of D-proline (D-3c), an exploitation the novel synthetic scheme 2 from L-α-amino acids (L-3) γ-amino (4) was studied. Reaction (S) (-)-ditosylate ((S) (-)-10a) easily derivable L-phenylalanine (L-3a), with diethyl potassiomalonate (3.0 eq.) in tetrahydrofuran, could directly give a mixture (R)-pyrrolidine-2-one ((R)-12a) (R) (-)-malonate ((R) (-)-13a) 70-80% yield. Some mechanistic studies revealed malonate reaction proceeded through regiospecific ring opening (+)-aziridine (+)-11a). Acidic hydrolysis crude (R)-12a (-)-13a afforded (-)-4a without racemization 49% yield based on (-)-10a. The same route applicable L-valine (L-3b), giving (+)-4b. However, (S)-4c be obtained L-proline (L-3c), by treatment (-)-iodide (-)-16c) prepared (-)-10c), anion, followed acidic hydrolysis. (+)-4b thus were readily converted into (-)-2a (+)-2b dehydration reduction. When synthesis 4-methyl-4-phenyl-2-cyclohexenone (18) examined using (+)-2b, (-)-18, being antipodal provided L-proline-derived (1) additives, successfully obtained.