A novel design of roof-shaped anthracene-fused chiral prolines as organocatalysts for asymmetric Mannich reactions

A new class of artificial anthracene-fused chiral proline catalysts has been synthesized from the Diels–Alder adduct of anthracene and maleic anhydride via lithiation/carboxylation of 6 as a key step. Chiral resolution of racemic amino acids was carried out through the formation of diastereomeric esters with (−)-menthol. The absolute configuration of the chiral amino acid was determined by X-ray crystallographic analysis. The utility of the catalyst was confirmed by effecting asymmetric three-component Mannich reactions between aldehyde, ketone, and amine (yield up to 76%, ee up to 90%).

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(1S,3aR,9aS)-4,9[1′,2′]Benzeno-1,3,3a,4,9,9a-hexahydro-1H-benz[f]isoindole-1-carboxylic acid (−)-menthyl esterC29H35NO2[α]D22 = +20.9 (c 1.62, MeOH)Source of chirality: diastereomeric ester resolutionAbsolute configuration: (1S,3aR,9aS)

(1R,3aS,9aR)-4,9[1′,2′]Benzeno-1,3,3a,4,9,9a-hexahydro-1H-benz[f]isoindole-1-carboxylic acid (−)-menthyl esterC29H35NO2[α]D22 = −93.1 (c 1.41, MeOH)Source of chirality: diastereomeric ester resolutionAbsolute configuration: (1R,3aS,9aR)

(1S,3aR,9aS)-4,9[1′,2′]Benzeno-1,3,3a,4,9,9a-hexahydro-1H-benz[f]isoindole-1-carboxylic acidC19H17NO2[α]D22 = +57.6 (c 0.62, MeOH)Source of chirality: diastereomeric ester resolutionAbsolute configuration: (1S,3aR,9aS)