An efficient synthesis of (+)-epi-cytoxazone via asymmetric organocatalysis

The catalytic enantioselective synthesis of (+)-epi-cytoxazone has been accomplished in four steps from p-methoxybenzaldehyde N-Boc-imine with good diastereo- and enantioselectivity. This approach involves asymmetric Mannich reaction of an aldehyde with N-Boc-imine using the novel 2-pyrrole-derived imidazolidinone as an organocatalyst.

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(2S,5S)-5-Benzyl-3-methyl-2-pyrrole-imidazolidine-4-oneC15H17N3OEe = 100%[α]D25=-145.1 (c 0.7, CHCl3)Source of chirality: (S)-phenylalanine methyl amideAbsolute configuration: (2S,5S)

(1R,2S)-[2-Benzyloxy-3-hydroxy-1-(4-methoxyphenyl)propyl]-carbamic acid tert-butyl esterC22H29NO5Ee = 94%[α]D23=-18.6 (c 0.6, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1R,2S)

(1R,2S)-[2,3-Dihydroxy-1-(4-methoxyphenyl)-propyl]-carbamic acid tert-butyl esterC15H23NO5Ee = 94%[α]D23=-36.1 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (1R,2S)

(4R,5S)-5-(Hydroxymethyl)-4-(4-methoxyphenyl)-oxazolidin-2-oneC11H13NO4Ee = 94%[α]D23=+32.8 (c 0.6, MeOH)Source of chirality: asymmetric synthesisAbsolute configuration: (4R,5S)