Organo-catalyzed enantioselective synthesis of some β-silyl γ-alkyl γ-butyrolactones as intermediates for natural products

The enantioselective synthesis of some β-silyl γ-alkyl γ-butyrolactones has been achieved by an organo-catalyzed Michael addition of enolizable aldehydes onto a silylmethylene malonate followed by a silicon-facilitated Bayer–Villiger oxidation of the β-silyl aldehyde adducts as the key step. γ-Alkyl γ-butenolides were obtained from the β-silyl γ-alkyl γ-butyrolactones by Fleming–Tamao oxidation of the silyl group to a hydroxy group and subsequent elimination. These butenolides are the advanced intermediates of some natural products such as (+)-γ-caprolactone, (+)-methylenolactocine, and (−)-quercus lactone.

Figure optionsDownload as PowerPoint slide

(4S,5R)-4-Dimethyl(phenyl)silyl-5-ethyl-4,5-dihydrofuran-2(3H)-oneC14H20O2Siee = 98%[α]D25=+31.8 (c 0.66, CHCl3)Source of chirality: asymmetric induction and (S)-diphenylprolinol trimethylsilyl etherAbsolute configuration: (4S,5R)

(4S,5R)-4-Dimethyl(phenyl)silyl-5-butyl-4,5-dihydrofuran-2(3H)-oneC16H24O2Siee = 99%[α]D25=+49.0 (c 1.51, CHCl3)Source of chirality: asymmetric induction and (S)-diphenylprolinol trimethylsilyl etherAbsolute configuration: (4S,5R)

(4S,5R)-4-Dimethyl(phenyl)silyl-5-pentyl-4,5-dihydrofuran-2(3H)-oneC17H26O2Siee = 98%[α]D25=+45.1 (c 0.82, CHCl3)Source of chirality: asymmetric induction and (S)-diphenylprolinol trimethylsilyl etherAbsolute configuration: (4S,5R)

(4S,5R)-5-Ethyl-4-hydroxy-4,5-dihydrofuran-2(3H)-oneC6H10O3ee = 98%[α]D29=+40.0 (c 0.8, CHCl3)Source of chirality: asymmetric induction and (S)-diphenylprolinol trimethylsilyl etherAbsolute configuration: (4S,5R)

(4S,5R)-5-Butyl-4-hydroxy-4,5-dihydrofuran-2(3H)-oneC8H14O3ee = 99%[α]D24=+35.1 (c 0.94, CHCl3)Source of chirality: asymmetric induction and (S)-diphenylprolinol trimethylsilyl etherAbsolute configuration: (4S,5R)

(4S,5R)-5-Pentyl-4-hydroxy-4,5-dihydrofuran-2(3H)-oneC9H16O3ee = 98%[α]D26=+36.0 (c 2.0, CHCl3)Source of chirality: asymmetric induction and (S)-diphenylprolinol trimethylsilyl etherAbsolute configuration: (4S,5R)

(2R,3S)-1,1-Di(ethoxycarbonyl)-2-dimethyl(phenyl)silylpentan-3-yl formateC20H30O6Siee = 98%[α]D25=+12.5 (c 3.7, CHCl3)Source of chirality: asymmetric induction and (S)-diphenylprolinol trimethylsilyl etherAbsolute configuration: (2R,3S)

(2R,3S)-1,1-Di(ethoxycarbonyl)-2-dimethyl(phenyl)silylheptan-3-yl formateC22H34O6Siee = 99%[α]D25=+12.8 (c 1.65, CHCl3)Source of chirality: asymmetric induction and (S)-diphenylprolinol trimethylsilyl etherAbsolute configuration: (2R,3S)

(2R,3S)-1,1-Di(ethoxycarbonyl)-2-dimethyl(phenyl)silyloctan-3-yl formateC23H36O6Siee = 98%[α]D23=+9.7 (c 1.85, CHCl3)Source of chirality: asymmetric induction and (S)-diphenylprolinol trimethylsilyl etherAbsolute configuration: (2R,3S)

(R)-5-Ethyl-2(5H)-furanoneC6H8O2ee = 98%[α]D24=-91.8 (c 1.46, MeOH)Source of chirality: asymmetric induction and (S)-diphenylprolinol trimethylsilyl etherAbsolute configuration: (R)

(R)-5-Butyl-2(5H)-furanoneC8H12O2ee = 99%[α]D24=-101.8 (c 2.16, CHCl3)Source of chirality: asymmetric induction and (S)-diphenylprolinol trimethylsilyl etherAbsolute configuration: (R)

(R)-5-Pentyl-2(5H)-furanoneC9H14O2ee = 98%[α]D24=-93.3 (c 2.53, CHCl3)Source of chirality: asymmetric induction and (S)-diphenylprolinol trimethylsilyl etherAbsolute configuration: (R)