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

Tseng, C; Terashima, S; Yamada, S

HERO ID

4932987

Reference Type

Journal Article

Year

1977

HERO ID 4932987
In Press No
Year 1977
Title Stereochemical Studies. XLIV. Exploitation of the New Synthetic Scheme for Chiral Additives Usable in Asymmetric Syntheses. Novel Syntheses of optically Active [gamma]-Amino Acids and Pyrrolidines from L-[alpha]-Amino Acids
Authors Tseng, C; Terashima, S; Yamada, S
Journal Chemical and Pharmaceutical Bulletin
Volume 25
Issue 1 (1977)
Page Numbers 29
Abstract   Aiming to prepare optically active pyrrolidines (2) which are usable as chiral additives for asymmetric syntheses via enamines, and whose absolute configurations can correspond to that of D-proline (D-3c), an exploitation of the novel synthetic scheme for 2 from L-α-amino acids (L-3) via optically active γ-amino acids (4) was studied. Reaction of (S) (-)-ditosylate ((S) (-)-10a) easily derivable from L-phenylalanine (L-3a), with diethyl potassiomalonate (3.0 eq.) in tetrahydrofuran, could directly give a mixture of (R)-pyrrolidine-2-one ((R)-12a) and (R) (-)-malonate ((R) (-)-13a) in 70-80% yield. Some mechanistic studies revealed that the malonate reaction proceeded through the regiospecific ring opening of (S) (+)-aziridine ((S) (+)-11a). Acidic hydrolysis of a crude mixture of (R)-12a and (R) (-)-13a afforded (R) (-)-4a without racemization in 49% yield based on (S) (-)-10a. The same synthetic route was applicable to L-valine (L-3b), giving (R) (+)-4b. However, (S)-4c could be obtained from L-proline (L-3c), by the treatment of (S) (-)-iodide ((S) (-)-16c) prepared from (S) (-)-ditosylate ((S) (-)-10c), with malonate anion, followed by acidic hydrolysis. (R) (-)-4a and (R) (+)-4b thus obtained were readily converted into (R) (-)-2a and (R) (+)-2b by dehydration and reduction. When the asymmetric synthesis of 4-methyl-4-phenyl-2-cyclohexenone (18) was examined by using (R) (-)-2a and (R) (+)-2b, (S) (-)-18, being antipodal to that provided by using L-proline-derived pyrrolidines (1) as chiral additives, was successfully obtained.
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