Diastereoselective alkylation of chiral 2-imidazolidinone glycolates: asymmetric synthesis of α-hydroxy carboxylic acids

Sodium enolates of chiral 2-imidazolidinone glycolates reacted with alkyl halides to produce α-alkylated products with high diastereoselectivities, which were readily removed by simple alkaline hydrolysis and were converted to the protected α-hydroxy carboxylic acids. The new stereogenic center was assigned the (R)-configuration by comparison with known compounds.

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(+)-(4S)-4-(1-Methylethyl)-1-phenyl-3-[(phenylmethoxy)acetyl]-2-imidazolidinoneC21H24N2O3[α]D20=+17.0 (c 4.16, CHCl3)Absolute configuration: S

(+)-(4S)-1-Phenyl-3-[(phenylmethoxy)acetyl]-4-(phenylmethyl)-2-imidazolidinoneC32H30N2O3[α]D20=+39.0 (c 4.45, CHCl3)Absolute configuration: S

(+)-4(S)-4-(1-Methylethyl)-3-[(2S)-1-oxo-3-phenyl-2-(phenylmethoxy)propyl]-1-phenyl-2-imidazolidinoneC28H30N2O3Ee = 96[α]D20=+35.1 (c 1.49, CHCl3)Absolute configuration: (2R,4S)

(+)-(4S)-4-(1-Methylethyl)-3-[(2R)-1-oxo-2-(phenylmethoxy)-4-pentenyl]-1-phenyl-2-imidazolidinoneC24H28N2O3Ee = 96[α]D20=+47.0 (c 5.57, CHCl3)Absolute configuration: (2R,4S)

(+)-4(S)-4-(1-Methylethyl)-3-[(2S)-1-oxo-2-(phenylmethoxy)propyl]-1-phenyl-2-imidazolidinoneC22H26N2O3Ee = 74[α]D20=+39.0 (c 0.73, CHCl3)Absolute configuration: (2R,4S)

(+)-4(S)-3-[(2S)-1-Oxo-3-phenyl-2-(phenylmethoxy)propyl]-1-phenyl-4-(1-phenylmethyl)-2-imidazolidinoneC32H30N2O3Ee = 96[α]D20=+32.0 (c 2.80, CHCl3)Absolute configuration: (2R,4S)

(+)-3-[(2R)-1-Oxo-2-(phenylmethoxy)-4- pentenyl]-1-phenyl-(4S)-4-(1-phenylmethyl)-2-imidazolidinoneC28H28N2O3Ee = 96[α]D20=+28.6 (c 0.71, CHCl3)Absolute configuration: (2R,4S)

(+)-3-[(2S)-1-Oxo-2-(phenylmethoxy)propyl]-1-phenyl-4(S)-4-(1-phenylmethyl)-2-imidazolidinoneC26H26N2O3Ee = 64[α]D20=+48.2 (c 0.50, CHCl3)Absolute configuration: (2R,4S)