Synthesis of enantiomerically pure hydroxylated pyrroline N-oxides from d-ribose

A convenient way to obtain enantiomerically pure hydroxylated pyrroline N-oxides is reported. The key step is the formation of ω-oxo enoates from d-ribose and a subsequent 1,3-azaprotio cyclotransfer reaction of the resulting oximino alkenoate derivatives. The stereochemistry of the nitrones obtained is discussed in relation to that of the starting compounds.

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Methyl (Z)-3-[(4R,5S)-5-(hydroxymethyl)-2,2-dimethyl-1,3-dioxolan-4-yl]-2-propenoateC10H16O5Ee = 100%[α]D25=-140 (c 1.2, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (4R,5S)

Methyl (Z)-3-[(4R,5R)-5-formyl-2,2-dimethyl-1,3-dioxolan-4-yl]-2-propenoateC10H14O5Ee = 100%[α]D25=+16.3 (c 0.65, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (4R,5R)

(3aR,4R,6aS)-4-(2-Methoxy-2-oxoethyl)-2,2-dimethyl-l-4,6a-dihydro-3aH-[1,3]dioxolo[4,5-c]pyrrol-5-ium-5-olateC10H15NO5Ee = 100%[α]D25=+11.0 (c 0.96, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (3aR,4R,6aS)

(Z)-tert-Butyl-3-{(4S,5R)-5-[(1R)-1,2-dihydroxyethyl]-2,2-dimethyl-1,3-dioxolan-4-yl}-2-propenoatesC14H24O6Ee = 100%[α]D25=+92.3 (c 1.24, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (3aR,5R,5(1R))

(Z)-tert-Butyl-3-[(4S,5S)-5-formyl-2,2-dimethyl-1,3-dioxolan-4-yl]-2-propenoateC10H16O5Ee = 100%[α]D25=+92.3 (c 1.24, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (4S,5S)

(3aS,4S,6aR)-4-[2-(tert-Butoxy)-2-oxoethyl]-2,2-dimethyl-4,6a-dihydro-3aH-[1,3]dioxolo[4,5-c]pyrrol-5-ium-5-olateC13H21NO5Ee = 100%[α]D25=-3.1 (c 3.4, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (3aS,4S,6aR)

(3aS,4R,6aR)-4-[2-(tert-butoxy)-2-oxoethyl]-2,2-dimethyl-4,6a-dihydro-3aH-[1,3]dioxolo[4,5-c]pyrrol-5-ium-5-olateC13H21NO5Ee = 100%[α]D25=-62.1 (c 1.76, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (3aS,4R,6aR)

(3aS,4S,6aR)-4-(2-Methoxy-2-oxoethyl)-2,2-dimethyl-6-[(trityloxy)methyl]-4,6a-dihydro-3aH-[1,3]dioxolo[4,5-c]pyrrol-5-ium-5-olateC30H31NO6Ee = 100%[α]D25=+5 (c 0.38, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (3aS,4R,6aR)