Crystallisation induced asymmetric transformation (CIAT) in the synthesis of furoylalanines and furylcarbinols

A new synthesis of enantiomerically highly enriched N-substituted furoylalanines has been developed. This process involves the combination of crystallisation induced asymmetric transformation (CIAT) and a conjugate addition of N-nucleophiles to furoylacrylic acids. Further transformations to furoylalanines and substituted furylcarbinols are also described.

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(2S,1′S)-4-(Furan-2-yl)-4-oxo-2-[(1′-phenylethyl)amino]-butanoic acidC16H17NO4De 98%[α]D25=+37.2 (c 0.9, MeOH/1 M HCl 3:1)Source of chirality: (S)-phenylethylamine, crystallisation induced asymmetric transformation (CIAT)Absolute configuration: (2S,1′S)

(2S,1′S)-4-(5-Methylfuran-2-yl)-4-oxo-2-[(1′-phenylethyl)amino]-butanoic acidC17H19NO4De 98%[α]D25=+50.3 (c 1.0, MeOH/1 M HCl 3:1)Source of chirality: (S)-phenylethylamine, crystallisation induced asymmetric transformation (CIAT)Absolute configuration: (2S,1′S)

(2S,1′S)-4-(5-Ethylfuran-2-yl)-4-oxo-2-[(1′-phenylethyl)amino]-butanoic acidC18H21NO4De 98%[α]D25=+50.7 (c 0.3, MeOH/1 M HCl 3:1)Source of chirality: (S)-phenylethylamine, crystallisation induced asymmetric transformation (CIAT)Absolute configuration: (2S,1′S)

(2S,1′R)-4-(Furan-2-yl)-2-[(2′-hydroxy-1′-phenylethyl)amino]-4-oxobutanoic acidC16H17NO5De 98%[α]D25=+23.2 (c 0.5, MeOH/1 M HCl 3:1)Source of chirality: (R)-2-amino-2-phenylethanol, crystallisation induced asymmetric transformation (CIAT)Absolute configuration: (2S,1′R)

(2S,1′R)-4-(5-Methylfuran-2-yl)-2-[(2′-hydroxy-1′-phenylethyl)amino]-4-oxobutanoic acidC17H19NO5De 98%[α]D25=+36.7 (c 0.6, MeOH/1 M HCl 3:1)Source of chirality: (R)-2-amino-2-phenylethanol, crystallisation induced asymmetric transformation (CIAT)Absolute configuration: (2S,1′R)

(2S,1′R)-4-(5-Ethylfuran-2-yl)-2-[(2′-hydroxy-1′-phenylethyl)amino]-4-oxobutanoic acidC18H21NO5De 92%[α]D25=+31.3 (c 0.5, MeOH/1 M HCl 3:1)Source of chirality: (R)-2-amino-2-phenylethanol, crystallisation induced asymmetric transformation (CIAT)Absolute configuration: (2S,1′R)

(2S,4R,1′S)-4-(Furan-2-yl)-4-hydroxy-2-[(1′-phenylethyl)amino]-butanoic acidC16H19NO4De 98%[α]D25=-37.2 (c 1.0, 0.1 M NaOH)Source of chirality: (S)-phenylethylamine, crystallisation induced asymmetric transformation (CIAT), stereoselective synthesisAbsolute configuration: (2S,4R,1′S)

(2S,4R,1′S)-4-Hydroxy-4-(5-methylfuran-2-yl)-2-[(1′-phenylethyl)amino]-butanoic acidC17H21NO4De 98%[α]D25=-44.0 (c 0.1, 0.1 M NaOH)Source of chirality: (S)-phenylethylamine, crystallisation induced asymmetric transformation (CIAT), stereoselective synthesisAbsolute configuration: (2S,4R,1′S)

(2S,4R,1′S)-4-(5-Ethylfuran-2-yl)-4-hydroxy-2-[(1′-phenylethyl)amino]-butanoic acidC18H23NO4De 98%[α]D25=-35.1 (c 1.0, 0.1 M NaOH)Source of chirality: (S)-phenylethylamine, crystallisation induced asymmetric transformation (CIAT), stereoselective synthesisAbsolute configuration: (2S,4R,1′S)

(2S,4R,1′R)-4-(Furan-2-yl)-4-hydroxy-2-[(2′-hydroxy-1′-phenylethyl)amino]-butanoic acidC16H19NO5·H2ODe 98%[α]D25=-43.9 (c 1.0, 0.1 M NaOH)Source of chirality: (R)-2-amino-2-phenylethanol, crystallisation induced asymmetric transformation (CIAT), stereoselective synthesisAbsolute configuration: (2S,4R,1′S)

(2S,4R,1′R)-4-Hydroxy-2-[(2′-hydroxy-1′-phenylethyl)amino]-4-(5-methylfuran-2-yl)-butanoic acidC17H21NO5·H2ODe 98%[α]D25=-43.1 (c 1.0, 0.1 M NaOH)Source of chirality: (R)-2-amino-2-phenylethanol, crystallisation induced asymmetric transformation (CIAT), stereoselective synthesisAbsolute configuration: (2S,4R,1′S)

(2S,4R,1′R)-4-(5-Ethylfuran-2-yl)-4-hydroxy-2-[(2′-hydroxy-1′-phenylethyl)amino]-butanoic acidC18H23NO5De 98%[α]D25=-40.5 (c 1.0, 0.1 M NaOH)Source of chirality: (R)-2-amino-2-phenylethanol, crystallisation induced asymmetric transformation (CIAT), stereoselective synthesisAbsolute configuration: (2S,4R,1′S)

(2S)-2-Amino-4-(furan-2-yl)-4-oxobutanoic acid hydrateC8H9NO4·H2OEe >98%[α]D25=+43.2 (c 0.5, 1 M HCl)Source of chirality: (R)-2-amino-2-phenylethanol, crystallisation induced asymmetric transformation (CIAT)Absolute configuration: (2S)

(2S)-2-Amino-4-(5-methylfuran-2-yl)-4-oxo-butanoic acid hydrateC9H11NO4·H2OEe >98%[α]D25=+49.1 (c 1.0, 1 M HCl)Source of chirality: (R)-2-amino-2-phenylethanol, crystallisation induced asymmetric transformation (CIAT)Absolute configuration: (2S)

(2S)-2-Amino-4-(5-ethylfuran-2-yl)-4-oxo-butanoic acid hydrateC10H13NO4·H2OEe 92%[α]D25=+40.4 (c 0.5, 1 M HCl)Source of chirality: (R)-2-amino-2-phenylethanol, crystallisation induced asymmetric transformation (CIAT)Absolute configuration: (2S)

(2R,4S,1″S)-4-[(1″-Phenylethyl)amino]-3,4-dihydro-2,2′-bifuran-5(2H)-oneC16H17NO3De 98%[α]D25=-189.6 (c 0.5, CHCl3)Source of chirality: (S)-phenylethylamine, crystallisation induced asymmetric transformation (CIAT), stereoselective synthesisAbsolute configuration: (2S,4R,1″S)

(2S,4S,1″S)-4-[(1″-Phenylethyl)amino]-3,4-dihydro-2,2′-bifuran-5(2H)-oneC16H17NO3De 99%[α]D25=+50.7 (c 1.0, CHCl3)Source of chirality: (S)-phenylethylamine, crystallisation induced asymmetric transformation (CIAT), stereoselective synthesisAbsolute configuration: (2S,4R,1″S)