Boron enolates of a hydantoin chiral auxiliary derived from l-phenylalanine: a versatile tool for asymmetric aldol reactions

The aldol reactions of boron enolates derived from a hydantoin chiral auxiliary derived from l-phenylalanine occur in good yields with high syn diastereoselectivity. Aldol adduct 4a is readily cleaved by hydrolysis to afford (2S,3S)-3-hydroxy-2-methyl-3-phenylpropionic acid 5a in good yield and in almost enantiomerically pure form.

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(S)-5-Benzyl-3-phenylhydantoinC16H14N2O2[α]D25=-159.8 (c 1.05, MeOH)Absolute configuration: (5S)Source of chirality: l-Phenylalanine

(S)-5-Benzyl-3-phenyl-1-propionylhydantoinC19H18N2O3[α]D25=-6.5 (c 1.02, CH2Cl2)Absolute configuration: (5S)Source of chirality: l-Phenylalanine

(2′S,3′S,5S)-5-Benzyl-3-phenyl-1-(3′-hydroxy-2′-methyl-3′-phenyl)propionylhydantoinC26H24N2O4[α]D25=+172.5 (c 1.00, CH2Cl2)Absolute configuration: (2′S,3′S,3S)Source of chirality: asymmetric aldol reaction

(2′S,3′S,5S)-5-Benzyl-3-phenyl-1-(3′-hydroxy-2′-methyl-3′-(2″,3″-dimethoxylphenyl)) propionylhydantoinC28H28N2O6[α]D25=+193.2 (c 1.01, CH2Cl2)Absolute configuration: (2′S,3′S,3S)Source of chirality: asymmetric aldol reaction

(2′S,3′S,5S)-5-Benzyl-3-phenyl-1-(3′-hydroxy-2′-methyl-3′-(4″-bromophenyl)) propionylhydantoinC26H23BrN2O4[α]D25=+222.5 (c 1.05, CH2Cl2)Absolute configuration: (2′S,3′S,3S)Source of chirality: asymmetric aldol reaction

(2′S,3′S,5S)-5-Benzyl-3-phenyl-1-(3′-hydroxy-2′-methyl-3′-(2″,4″-dichlorophenyl))propionylhydantoinC26H22Cl2N2O4[α]D25=+177.3 (c 1.02, CH2Cl2)Absolute configuration: (2′S,3′S,3S)Source of chirality: asymmetric aldol reaction

(2′S,3′S,5S)-5-Benzyl-3-phenyl-1-(3′-hydroxy-2′-methyl-3′-(2″-nitrophenyl))propionylhydantoinC26H23N3O6[α]D25=+185.5 (c 1.00, CH2Cl2)Absolute configuration: (2′S,3′S,3S)Source of chirality: asymmetric aldol reaction

(2′S,3′S,5S)-5-Benzyl-3-phenyl-1-(3′-hydroxy-2′-methyl-3′-(3″-nitrophenyl))propionylhydantoinC26H23N3O6[α]D25=+180.7 (c 1.01, CH2Cl2)Absolute configuration: (2′S,3′S,3S)Source of chirality: asymmetric aldol reaction

(2′S,3′S,5S)-5-Benzyl-3-phenyl-1-(3′-hydroxy-2′-methyl-3′-(4″-cyanophenyl))propionylhydantoinC27H23N3O4[α]D25=+202.2 (c 1.00, CH2Cl2)Absolute configuration: (2′S,3′S,3S)Source of chirality: asymmetric aldol reaction

(2S,3S)-3-hydroxy-2-methyl-3-phenylpropanoic acidC10H12O3[α]D25=-29.8 (c 0.82, CH2Cl2)Absolute configuration: (2S,3S)Source of chirality: asymmetric aldol reaction