Chiral diphenylperhydroindolinol silyl ether catalyzed domino oxa-Michael–aldol condensations for the asymmetric synthesis of benzopyrans

Asymmetric domino oxa-Michael–aldol reactions between trans-cinnamaldehydes and salicylic aldehyde derivatives have been developed. Using (2S,3aS,7aS)-diphenylperhydro indolinol silyl ether 4i as the catalyst, most corresponding chiral benzopyrans can be obtained with excellent chemo- and enantioselectivities.

Figure optionsDownload as PowerPoint slide

(R)-6-Bromo-2-(4-nitrophenyl)-2H-chromene-3-carbaldehydeC16H10BrNO4ee = 83%[α]D20=-41.4 (c 0.4, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2R)

(R)-6-Bromo-2-(2-nitrophenyl)-2H-chromene-3-carbaldehydeC16H10BrNO4ee = 95%[α]D20=+273.0 (c 0.4, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2R)

(R)-2-(4-Fluorophenyl)-2H-chromene-3-carbaldehydeC16H11FO2ee = 93%[α]D20=-42.6 (c 0.2, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2R)

(R)-6-Bromo-2-(4-fluorophenyl)-2H-chromene-3-carbaldehydeC16H10BrFO2ee = 83%[α]D20=+29.4 (c 0.3, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2R)

(R)-6-Chloro-2-(4-fluorophenyl)-2H-chromene-3-carbaldehydeC16H10ClFO2ee = 83%[α]D20=+18.6 (c 0.3, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2R)

(S)-2-(2,4,5-Trifluorophenyl)-2H-chromene-3-carbaldehydeC16H9F3O2ee = 94%[α]D20=+42.0 (c 0.6, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S)

(S)-7-Methoxy-2-(2,4,5-trifluorophenyl)-2H-chromene-3-carbaldehydeC17H11F3O3ee = 71%[α]D20=-30.5 (c 0.3, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S)

(R)-6-Bromo-2-(4-methoxyphenyl)-2H-chromene-3-carbaldehydeC17H13BrO3ee = 94%[α]D20=+36.1 (c 0.6, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2R)