Asymmetric oxidation of enol phosphates to α-hydroxy ketones using Sharpless reagents and a fructose derived dioxirane

The asymmetric oxidation of a variety of differently substituted, acyclic and cyclic enol phosphates using the Sharpless AD-reagents AD-mix-α and AD-mix-β, and a fructose derived chiral ketone as a catalyst, afforded the corresponding α-hydroxy ketones in high enantioselectivity and good yield. The influence of steric and electronic factors of the substrates on the facial stereoselectivity in the reported oxidations was studied.

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(2S)-2-Hydroxy-1-phenyl-1-propan-1-oneC9H10O2ee = 98.6% (HPLC)[α]D20=-96.4 (c 0.7, CHCl3)Source of chirality: asymmetric synthesis by AD-mix-αAbsolute configuration (S)

(2S)-2-Hydroxy-1-(4-methoxy-phenyl)-1-propan-1-oneC10H12O3ee = 100% (HPLC)[α]D20=-79 (c 0.7, CHCl3)Source of chirality: asymmetric synthesis by AD-mix-αAbsolute configuration (S)

(2S)-2-Hydroxy-1-phenyl-1-butan-1-oneC10H12O2ee = 92% (HPLC)[α]D20=-34.4 (c 0.7, CHCl3)Source of chirality: asymmetric synthesis by AD-mix-αAbsolute configuration (S)

(2R)-2-Hydroxy-1,2-diphenyl-ethanoneC14H12O2ee = 100% (HPLC)[α]D20=-142 (c 0.7, CHCl3)Source of chirality: asymmetric synthesis by AD-mix-βAbsolute configuration (R)

(2R)-2-Hydroxy-3,4-dihydro-2H-naphthalen-1-oneC10H10O2ee = 88% (HPLC)[α]D20=+14.7 (c 0.6, CHCl3)Source of chirality: asymmetric synthesis with a chiral dioxiraneAbsolute configuration (R)

(2R)-3-Hydroxy-2,3-dihydro-4H-chromen-4-oneC9H8O3ee = 92% (HPLC)[α]D20=+82.7 (c 0.85, CHCl3)Source of chirality: asymmetric synthesis with a chiral dioxiraneAbsolute configuration (R)

(3S)-3-Hydroxy-2,3-dihydro-1H-phenanthren-4-oneC14H12O2ee = 84% (HPLC)[α]D20=-20.7 (c 0.8, CHCl3)Source of chirality: asymmetric synthesis with a chiral dioxiraneAbsolute configuration (S)

(2S)-2-Hydroxy-2-methyl-1-indanoneC10H10O2ee = 12% (HPLC)[α]D20=-3.7 (c 0.4, CHCl3)Source of chirality: asymmetric synthesis with a chiral dioxiraneAbsolute configuration (S)

(2S)-2-Hydroxy-1-phenyl-1-pentan-1-oneC11H14O2Ee = 76% (HPLC)[α]D20=-10.2 (c 0.14, CHCl3)Source of chirality: asymmetric synthesis with a chiral dioxiraneAbsolute configuration (S)