Stereoselective synthesis of vicinal aminodiols, diamines and diaminols by the use of enantiopure aldehydes in the three-component aromatic Mannich-type reaction

A short and stereoselective synthesis of vicinal aminodiols, diamines and diaminols obtained in good yields, through a three-component aromatic Mannich-type reaction, is reported. Enantiopure aldehydes containing stereogenic centres and functionalized with variously protected amino and hydroxy groups successfully afforded enantiopure aminoalkylnaphthols. Conformational analysis, compared with 1H NMR data of the products obtained, allows the attribution of the absolute configuration, also confirmed by X-ray analysis.

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1-{(S)-Benzylamino[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl}-2-naphtholC23H25NO3Ee = 98%[α]D20=-26.2 (c 0.38, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S,S)

1-{(R)-Benzylamino[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl}-2-naphtholC23H25NO3Ee = 98%[α]D20=-12.9 (c 0.39, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1R,4S)

1-(S)-(4S)-2,2-Dimethyl-1,3-dioxolan-4-yl(pyrrolidin-1-yl)methyl-2-naphtholC20H25NO3Ee = 98%[α]D20=+0.6 (c 0.49, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S,S)

1-((S)-(4S)-2,2-Dimethyl-1,3-dioxolan-4-yl{[(1R)-1-phenylethyl]amino}methyl)-2-naphtholC24H27NO3Ee = 98%[α]D20=-44.5 (c 0.74, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,4S,1′R)

1-{(S)-(1R)-1-(1-Naphthyl)ethan-1-amine[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl}-2-naphtholC28H29NO3Ee = 98%[α]D20=-111.9 (c 1.15, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,4S,1′R)

Benzyl (2S)-2-[(S)-benzylamino(2-hydroxy-1-naphthyl)methyl]pyrrolidine-1-carboxylateC30H30N2O3Ee = 98%[α]D20=-15.8 (c 3.65, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S,S)

tert-Butyl (4R)-4-[(S)-benzylamino(2-hydroxy-1-naphthyl)methyl]-2,2-dimethyl-1,3-oxazolidine-3-carboxylateC28H34N2O4Ee = 98%[α]D20=+3.5 (c 1.44, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1′S,4R)

tert-Butyl-N-[(S,S)-1-benzyl-2-(benzylamino)-2-(2-hydroxy-1-naphthyl)ethyl]carbamateC31H34N2O3Ee = 98%[α]D20=+3.75 (c 2.21, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S,S)

(2S,3S)-3-(Benzylamino)-3-(2-hydroxy-1-naphthyl)propane-1,2-diolC20H21NO3Ee = 98%[α]D20=-0.9 (c 0.64, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S,S)

(S,S)-3-(2-Hydroxy-1-naphthyl)-3-pyrrolidin-1-ylpropane-1,2-diolC17H21NO3Ee = 98%[α]D20=-0.8 (c 0.91, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S,S)

(S,S)-3-(2-Hydroxy-1-naphthyl)-3-{[(1′R)-1′-phenylethyl]amino}propane-1,2-diolC21H23NO3Ee = 98%[α]D20=-0.8 (c 1.5, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3S,1′R)

1-{(S)-(Benzylamino)[(2S)pyrrolidin-2-yl]methyl}-2-naphtholC22H24N2OEe = 98%[α]D20=+2.7 (c 1.30, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S,S)

1-[(1S,2R)-2-Amino-1-(benzylamino)-3-hydroxypropyl]-2-naphtholC20H22N2O2Ee = 98%[α]D20=+1.1 (c 0.46, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1S,2R)

1-[(S,S)-2-Amino-1-(benzylamino)-3-phenylpropyl]-2-naphtholC26H26N2OEe = 98%[α]D20=+1.9 (c 1.2, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S,S)

1-[(1R,2S)-2-Amino-1-(benzylamino)-3-phenylpropyl]-2-naphtholC26H26N2OEe = 98%[α]D20=-0.5 (c 1.44, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1R,2S)