Synthesis of enantiopure 4-amino-3-hydroxymethyl-tetrahydroquinolines via an intramolecular nitrone cycloaddition

Enantiopure 4-amino-3-hydroxymethyl-1,2,3,4-tetrahydroquinolines are synthesized by using an intramolecular cycloaddition of chiral nitrones prepared from aldehydes 5 and (R)-α-(hydroxymethyl)benzylhydroxylamine. Reaction times of the nitrone cycloaddition were optimized by activation under MW-assisted conditions. The absolute configuration of the products was determined by X-ray analysis.

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(αR,3aR,9bR)-5-Carbethoxy-1-(1-phenyl-2-hydroxyethyl)-7,8,9-trimethoxy-1,3a,4,9b-tetrahydro-3H-isoxazolo[4,3-c]quinolineC24H30N2O7[α]D23=-19.5 (c 0.7, CHCl3)Source of chirality: (R)-1-phenyl-2-hydroxyethylhydroxylamineAbsolute configuration: (αR,3aR,9bR)

(αR,3aS,9bS)-5-Carbethoxy-1-(1-phenyl-2-hydroxyethyl)-7,8,9-trimethoxy-1,3a,4,9b-tetrahydro-3H-isoxazolo[4,3-c]quinolineC24H30N2O7[α]D23=-63.5 (c 1.0, CHCl3)Source of chirality: (R)-1-phenyl-2-hydroxyethylhydroxylamineAbsolute configuration: (αR,3aS,9bS)

(αR,3aR,9bR)-5-Carbethoxy-1-(1-phenyl-2-hydroxyethyl)-7-methoxy-8-methyl-1,3a,4,9b-tetrahydro-3H-isoxazolo[4,3-c]quinolineC23H28N2O5[α]D23=-11.1 (c 0.9, CHCl3)Source of chirality: (R)-1-phenyl-2-hydroxyethylhydroxylamineAbsolute configuration: (αR,3aR,9bR)

(αR,3aS,9bS)-5-Carbethoxy-1-(1-phenyl-2-hydroxyethyl)-7-methoxy-8-methyl-1,3a,4,9b-tetrahydro-3H-isoxazolo[4,3-c]quinolineC23H28N2O5[α]D23=-9.3 (c 0.8, CHCl3)Source of chirality: (R)-1-phenyl-2-hydroxyethylhydroxylamineAbsolute configuration: (αR,3aS,9bS)

(αR,3aR,9bR)-5-Carbethoxy-1-(1-phenyl-2-hydroxyethyl)-1,3a,4,10b-tetrahydro-3H,8H-[1,3]dioxolo[4,5-g]isoxazolo[4,3-c]quinolineC22H24N2O6[α]D23=-7.9 (c 1.0, CHCl3)Source of chirality: (R)-1-phenyl-2-hydroxyethylhydroxylamineAbsolute configuration: (αR,3aR,10bR)

(αR,3aS,9bS)-5-Carbethoxy-1-(1-phenyl-2-hydroxyethyl)-1,3a,4,10b-tetrahydro-3H,8H-[1,3]dioxolo[4,5-g]isoxazolo[4,3-c]quinolineC22H24N2O6[α]D23=-7.4 (c 1.1, CHCl3)Source of chirality: (R)-1-phenyl-2-hydroxyethylhydroxylamineAbsolute configuration: (αR,3aS,10bS)

(3R,4R)-4-Amino-1-carbethoxy-3-hydroxymethyl-5,6,7-trimethoxy-1,2,3,4-tetrahydroquinolineC16H24N2O6[α]D23=+23.3 (c 1.3, CHCl3)Source of chirality: (R)-1-phenyl-2-hydroxyethylhydroxylamineAbsolute configuration: (3R,4R)

(3S,4S)-4-Amino-1-carbethoxy-3-hydroxymethyl-5,6,7-trimethoxy-1,2,3,4-tetrahydroquinolineC16H24N2O6[α]D23=-22.9 (c 1.1, CHCl3)Source of chirality: (R)-1-phenyl-2-hydroxyethylhydroxylamineAbsolute configuration: (3S,4S)

(3R,4R)-4-Amino-1-carbethoxy-3-hydroxymethyl-7-methoxy-6-methyl-1,2,3,4-tetrahydroquinolineC15H22N2O4[α]D23=+29.3 (c 0.6, CHCl3)Source of chirality: (R)-1-phenyl-2-hydroxyethylhydroxylamineAbsolute configuration: (3R,4R)

(3S,4S)-4-Amino-1-carbethoxy-3-hydroxymethyl-7-methoxy-6-methyl-1,2,3,4-tetrahydroquinolineC15H22N2O4[α]D23=-29.9 (c 0.5, CHCl3)Source of chirality: (R)-1-phenyl-2-hydroxyethylhydroxylamineAbsolute configuration: (3S,4S)

(7R,8R)-8-Amino-5-carbethoxy-7-hydroxymethyl-5,6,7,8-tetrahydro-[1,3]dioxolo[4,3-c]quinolineC14H18N2O5[α]D23=+25.9 (c 0.6, CHCl3)Source of chirality: (R)-1-phenyl-2-hydroxyethylhydroxylamineAbsolute configuration: (7R,8R)

(7S,8S)-8-Amino-5-carbethoxy-7-hydroxymethyl-5,6,7,8-tetrahydro-[1,3]dioxolo[4,3-c]quinolineC14H18N2O5[α]D23=-25.1 (c 0.5, CHCl3)Source of chirality: (R)-1-phenyl-2-hydroxyethylhydroxylamineAbsolute configuration: (7R,8R)