An efficient enzymatic approach to (S)-1-aryl-allylamines

A range of 1-aryl-allylamines were prepared in moderate to excellent enantioselectivity (ee 63.5%→99.9%) using lipase B from a Candida antarctica catalyzed resolution of racemic amines. This is the first time that CaLB has been used for the resolution of 1-aryl-allylamines. Racemic amines were prepared starting from aromatic aldehydes with a [3,3]-sigmatropic rearrangement of the acyclic imidates as the key step followed by trichloroacetamidate hydrolysis. Aldehydes were converted into acrylic esters using Knoevenagel reaction. After reduction, the corresponding alcohols were used for the preparation of trichloroacetimidates, which were then used in an Overman rearrangement.

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(S)-1-(1-Naphthalenyl)-prop-2-en-1-amineC13H13NEe >99.9%[α]D25=-46.0 (c 0.9, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (1S)

(S)-1-(4-Methylphenyl)-prop-2-en-1-amineC10H13NEe 98.9%[α]D25=-9.7 (c 1.1, CH2Cl2)Source of chirality: enzymatic resolutionAbsolute configuration: (1S)

(S)-1-(4-Methylnaphthalen-1-yl)-prop-2-en-1-amineC14H15NEe >99.9%[α]D25=-40.2 (c 3.2, CH2Cl2)Source of chirality: enzymatic resolutionAbsolute configuration: (1S)

(S)-1-Phenyl-prop-2-en-1-amineC9H11NEe >99.9%[α]D25=-10.2 (c 3.3, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: (1S)