Diastereo-controlled Diels–Alder cycloadditions of erythrose benzylidene-acetal 1,3-butadienes by 4-substituted-1,2,4-triazoline-3,5-dione: Evidence for the stereoelectronic effects on the dienes

Erythrose benzylidene-acetal 1,3-butadienes are studied as partners in Diels–Alder cycloadditions. A high diastereofacial improvement is found in cases where both the alcohol function is protected and a π–π interaction between the diene and dienophile is possible. Several competing factors have been studied independently in order to explain its influence on the selectivity of the cycloadditions.

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(S)-5-((2′R,4′S,5′R)-5-Hydroxy-2-phenyl-1,3-dioxan-4-yl)-2-phenyl-5,8-dihydro-1H-[1,2,4]triazolo[1,2-a]pyridazine-1,3(2H)-dioneC22H21N3O5[α]D20=-327.5 (c 1.60 g/100 mL, CHCl3)Source: d-glucose; asymmetric synthesisAbsolute configurations: 5S,2′R,4′S,5′R

(S)-5-((2′R,4′S,5′R)-5-Methoxy-2-phenyl-1,3-dioxan-4-yl)-2-phenyl-5,8-dihydro-1H-[1,2,4]triazolo[1,2-a]pyridazine-1,3(2H)-dioneC23H23N3O5[α]D20=-301.2 (c 2.25 g/100 mL, CHCl3)Source: d-glucose; asymmetric synthesisAbsolute configurations: 5S,2′R,4′S,5′R

(R)-5-((2′R,4′S,5′R)-5-Hydroxy-2-phenyl-1,3-dioxan-4-yl)-2-phenyl-5,8-dihydro-1H-[1,2,4]triazolo[1,2-a]pyridazine-1,3(2H)-dioneC22H21N3O5[α]D20=+129.4 (c 1.80 g/100 mL, CH3Cl)Source: d-glucose; asymmetric synthesisAbsolute configurations: 5R,2′R,4′S,5′R

(5S,8S)-Ethyl 8-((2′R,4′S,5′R)-5-hydroxy-2-phenyl-1,3-dioxan-4-yl)-1,3-dioxo-2-phenyl-2,3,5,8-tetrahydro-1H-[1,2,4]triazolo[1,2-a]pyridazine-5-carboxylateC25H25N3O7[α]D20=+0.8 (c 1.50 g/100 mL, CHCl3)Source: d-glucose; asymmetric synthesisAbsolute configurations: 5S,8S,2′R,4′S,5′R

(5R,8R)-Ethyl 8-((2R,4S,5R)-5-hydroxy-2-phenyl-1,3-dioxan-4-yl)-1,3-dioxo-2-phenyl-2,3,5,8-tetrahydro-1H-[1,2,4]triazolo[1,2-a]pyridazine-5-carboxylateC25H25N3O7[α]D20=-18.9 (c 1.10 g/100 mL, CHCl3)Source: d-glucose; asymmetric synthesisAbsolute configurations: 5R,8R,2′R,4′S,5′R

(5S)-7-(t-Butyldimethylsilyloxy)-5-((2′R,4′S,5′R)-5-(t-butyldimethylsilyloxy)-2-phenyl-1,3-dioxan-4-yl)-2-phenyl-5,8-dihydro-1H-pyrazolo[1,2-a]pyridazine-1,3(2H)-dioneC34H49N3O6Si2[α]D20=-139.0 (c 2.65 g/100 mL, CHCl3)Source: d-glucose; asymmetric synthesisAbsolute configurations: 5S,2′R,4′S,5′R

(S)-5-((2′R,4′S,5′R)-5-Hydroxy-2-methyl-1,3-dioxan-4-yl)-2-phenyl-5,8-dihydro-1H-[1,2,4]triazolo[1,2-a]pyridazine-1,3(2H)-dioneC17H19N3O5[α]D20=-198.1 (c 0.50 g/100 mL, CHCl3)Source: d-glucose; asymmetric synthesisAbsolute configuration: 5S,2′R,4′S,5′R

(S)-5-((2′R,4′S,5′R)-5-Hydroxy-2-methyl-1,3-dioxan-4-yl)-2-phenyl-5,8-dihydro-1H-[1,2,4]triazolo[1,2-a]pyridazine-1,3(2H)-dioneC18H21N3O5[α]D20=-276.7 (c 1.25 g/100 mL, CHCl3)Source: d-glucose; asymmetric synthesisAbsolute configuration: 5S,2′R,4′S,5′R