Stereoselective syntheses of siphonarienal and siphonarienone

The asymmetric total synthesis of marine polypropionate natural products siphonarienal and siphonarienone has been achieved from a common precursor 3. The key transformations of this synthesis are the diastereoselective oxidative kinetic resolution, Wittig olefination, Grignard reaction, and Evans asymmetric alkylation for the installation of a third stereogenic center of the target molecules from commercially available starting materials.

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(2R,4S)-5-(tert-Butyldiphenylsilyl)oxy)-2,4-dimethylpental-1-olC23H34O2Si[α]D25 = +1.75 (c 0.25, CHCl3)Source of chirality: Oxidative kinetic resolutionAbsolute configuration: (2R,4S)

(4R,6S,E)-Ethyl 7-((tert-butyldiphenylsilyl)oxy)-4,6-dimethylhept-2-enoateC27H38O3Si[α]D25 = +25.5 (c 1.0, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (4R,6S,E)

(4S,6S)-Ethyl 7-((tert-butyldiphenylsilyl)oxy)-4,6-dimethylheptanoateC27H40O3Si[α]D25 = +5.4 (c 1.0, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (4S,6S)

(4S,6S)-7-((tert-Butyldiphenylsilyl)oxy)-4,6-dimethylheptanoic acidC25H36O3Si[α]D25 = +8.0 (c 1.0, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (4S,6S)

(R)-4-Benzyl-3-((4S,6S)-7-((tert-butyldiphenylsilyl)oxy)-4,6-dimethylheptanoyl)oxazolidin-2-oneC35H45NO4Si[α]D25 = +40.0 (c 1.0, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (R) (4S,6S)

(R)-4-Benzyl-3-((2R,4R,6S)-7-((tert-butyldiphenylsilyl)oxy)-2,4,6-trimethyl heptanoyl)oxazolidin-2-oneC34H45NO4Si[α]D25 = +42.8 (c 1.0, CHCl3)Source of chirality: Evans asymmetric alkylationAbsolute configuration: (R) (2R,4R,6S)

(2R,4S,6S)-7-((tert-Butyldiphenylsilyl)oxy)-2,4,6-trimethylheptan-1-olC26H40O2Si[α]D25 = −6.0 (c 1.0, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (2R,4S,6S)

tert-Butyldiphenyl(((2S,4S,6S)-2,4,6-trimethylnonyl)oxy)silaneC28H44OSi[α]D25 = −7.0 (c 1.0, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (2S,4S,6S)

(2S,4S,6S)-2,4,6-Trimethylnonan-1-olC12H26O[α]D25 = −12.0 (c 1.0, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (2S,4S,6S)

(4S,6S,8S,E)-Ethyl 2,4,6,8-trtramethylundec-2-enoateC17H32O2[α]D25 = +18.1 (c 0.9, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (4S,6S,8S,E)

(4S,6S,8S,E)-2,4,6,8-Tetramethyl-2-undecenalC15H18O[α]D25 = +16.1 (c 1.1, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (4S,6S,8S,E)

(6S,8S,10S,E)-4,6,8,10-Tetramethyltridec-4-3-oneC17H32O[α]D25 = +22.4 (c 1.0, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (6S,8S,10S,E)