Benzo[d]imidazole and Aliphatic α-Amino Acid Derived Primary Amines in Asymmetric Aldol Reactions

Abstract

Starting from essential α-amino acids, four new benzo[d]imidazole and alkyl-chain-substituted primary amines were synthesized. The reaction sequence involves activation of the Boc-amino acid carboxylic acid, reaction with o-phenylenediamine, and subsequent cyclization to benzo[d]imidazole. N-Methylation and final Boc group removal afforded four new primary amines. The synthesized amines were preliminarily applied as organocatalysts in an asymmetric version of the aldol reaction between 4-nitrobenzaldehyde and acetone/cyclohexanone, achieving chemical yields of 40–64% and ee and de values up to 65 and 96%, respectively.

Key words

benzo[d]imidazole - primary amine - α-amino acid - asymmetric aldol reaction - organocatalysis

• References and Notes

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For selected recent applications of chiral imidazole derivatives in asymmetric catalysis, see:
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• 11 Aldol Reaction; General Procedure: A solution of catalyst 1–4 (0.09 mmol) in acetone or cyclohexanone (7.5 mL) was treated with TFA (3.5 μL, 0.045 mmol) at 20 °C for 5 min, whereupon 4-nitrobenzaldehyde (151 mg, 1.0 mmol) was added and the reaction was stirred for 24 h. The solvent was evaporated and the residue was purified by column chromatography (SiO₂; EtOAc–hexane, 1:1).
• 12 Enantiomeric excesses were determined by chiral phase HPLC. For 17: Daicel Chiralpak AS-H; n-hexane–i-PrOH, 70:30; flow rate 0.5 mL/min; λ = 254 nm, t _R = 25.32, 33.65 min. For 18: Daicel Chiralpak AD-H; n-hexane–i-PrOH, 80:20; flow rate 0.5 mL/min; λ = 254 nm; t _R = 22.69 (syn), 24.34 (syn), 26.35 (anti), 33.26 (anti) min.