Efficient asymmetric hydrogenation of the C–C double bond of 2-methyl- and 2,3-dimethyl-N-phenylalkylmaleimides by Aspergillus fumigatus

Eight N-phenylalkylmaleimides (four 2-methyl-N-phenylalkylmaleimides and four 2,3-dimethyl-N-phenylalkylmaleimides with an alkyl chain (CH2)n (n = 1–4) between the imide N and the benzene ring) were subjected to biotransformation using the fungal strain Aspergillus fumigatus ATCC 26934. All compounds were reduced enantioselectively to their respective succinimides: (R)-2-methyl-N-phenylalkylsuccinimides and (2R,3R)-2,3-dimethyl-N-phenylalkylsuccinimides, with satisfactory conversion rates and high stereoisomeric excesses. NMR analysis using the chiral shift reagent Eu(hfc)3 showed that enantiomeric excesses were >99%.

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(+)-2-Methyl-N-bencylsuccinimideC12H13NO2Ee >99%[α]D27=+19.7±1.2 (c 0.73, CHCl3)Source of chirality: hydrogenation by AspergillusfumigatusAbsolute configuration: (R)

(+)-2-Methyl-N-phenethylsuccinimideC13H15NO2Ee >99%[α]D27=+7.0±1.5 (c 0.73, CHCl3)Source of chirality: hydrogenation by AspergillusfumigatusAbsolute configuration: (R)

(+)-2-Methyl-N-propylphenylsuccinimideC14H17NO2Ee >99%[α]D27=+1.5±0.8 (c 1.50, CHCl3)Source of chirality: hydrogenation by AspergillusfumigatusAbsolute configuration: (R)

(+)-2-Methyl-N-butylphenylsuccinimideC15H19NO2Ee >99%[α]D27=+1.3±0.3 (c 0.45, CHCl3)Source of chirality: hydrogenation by AspergillusfumigatusAbsolute configuration: (R)

(+)-2,3-Dimethyl-N-bencylsuccinimideC13H15NO2Ee >99%[α]D27=+38.0±2.2 (c 0.31, CHCl3)Source of chirality: hydrogenation by AspergillusfumigatusAbsolute configuration: (2R,3R)

(+)-2,3-Dimethyl-N-phenethylsuccinimideC14H17NO2Ee >99%[α]D27=+40.8±0.6 (c 0.36, CHCl3)Source of chirality: hydrogenation by AspergillusfumigatusAbsolute configuration: (2R,3R)

(+)-2,3-Dimethyl-N-propylphenylsuccinimideC15H19NO2Ee >99%[α]D27=+39.4±0.90 (c 0.36, CHCl3)Source of chirality: hydrogenation by AspergillusfumigatusAbsolute configuration: (2R,3R)

(+)-2,3-Dimethyl-N-butylphenylsuccinimideC16H21NO2Ee >99%[α]D27=+38.3±0.6 (c 0.36, CHCl3)Source of chirality: hydrogenation by AspergillusfumigatusAbsolute configuration: (2R,3R)