Formal synthesis of herbarumin III

An enantioselective synthesis of herbarumin III is described employing Jacobsen’s hydrolytic kinetic resolution and Sharpless asymmetric dihydroxylation as the key steps.

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(S)-2-(Chloromethyl)oxiraneC3H5ClOEe >99%[α]D25=+30.6 (c 1.2, MeOH)Source of chirality: Jacobsen’s hydrolytic kinetic resolutionAbsolute configuration: (S)

(S)-2-AllyloxiraneC5H8O[α]D25=-16.2 (neat)Source of chirality: Jacobsen’s hydrolytic kinetic resolutionAbsolute configuration: (S)

(R)-Hept-1-en-4-olC7H14O[α]D25=-17.4 (c 1.1, CHCl3)Source of chirality: Jacobsen’s hydrolytic kinetic resolutionAbsolute configuration: (R)

(R)-tert-Butyl(hept-1-en-4-yloxy)dimethylsilaneC12H15N3O[α]D25=-21.2 (c 1.0, CHCl3)Source of chirality: Jacobsen’s hydrolytic kinetic resolutionAbsolute configuration: (R)

(R,E)-Ethyl 5-(tert-butyldimethylsilyloxy)oct-2-enoateC16H32O3Si[α]D25=-23.1 (c 1.1, CHCl3)Source of chirality: Jacobsen’s hydrolytic kinetic resolutionAbsolute configuration: (R)

(2S,3R,5R)-Ethyl 5-(tert-butyldimethylsilyloxy)-2,3-dihydroxyoctanoateC16H34O5Si[α]D25=-11.2 (c 1.0, CHCl3)Source of chirality: Jacobsen’s hydrolytic kinetic resolution, Sharpless asymmetric dihydroxylationAbsolute configuration: (2S,3R,5R)

(4S,5R)-Ethyl 5-((R)-2′-(tert-butyldimethylsilyloxy)pentyl)-2,2-dimethyl-1,3-dioxolane-4- carboxylateC19H38O5Si[α]D25=-24.1 (c 0.8, CHCl3)Source of chirality: Jacobsen’s hydrolytic kinetic resolution, Sharpless asymmetric dihydroxylationAbsolute configuration: (2′R,4S,5R)

((4R,5R)-5-((R)-2′-(tert-Butyldimethylsilyloxy)pentyl)-2,2-dimethyl-1,3-dioxolan-4-yl)methanolC17H36O4Si[α]D25=-16.2 (c 1.1, CHCl3)Source of chirality: Jacobsen’s hydrolytic kinetic resolution, Sharpless asymmetric dihydroxylationAbsolute configuration: (2′R,4R,5R)

tert-Butyl((R)-1-((4R,5S)-5-(iodomethyl)-2,2-dimethyl-1,3-dioxolan-4-yl)pentan-2-yloxy)dimethylsilaneC17H35IO3Si[α]D25=-64.7 (c 1.0, CHCl3)Source of chirality: Jacobsen’s hydrolytic kinetic resolution, Sharpless asymmetric dihydroxylationAbsolute configuration: (4R,5S)

(3R,5R)-5-(tert-Butyldimethylsilyloxy)oct-1-en-3-olC14H30O2Si[α]D25=-32.1 (c 1.0, CHCl3)Source of chirality: Jacobsen’s hydrolytic kinetic resolution, Sharpless asymmetric dihydroxylationAbsolute configuration: (3R,5R)

tert-Butyl((4R,6R)-6-(4-methoxybenzyloxy)oct-7-en-4-yloxy)dimethylsilaneC22H38O3Si[α]D25=-38.3 (c 1.1, CHCl3)Source of chirality: Jacobsen’s hydrolytic kinetic resolution, Sharpless asymmetric dihydroxylationAbsolute configuration: (4R,6R)

(4R,6R)-6-(4-Methoxybenzyloxy)oct-7-en-4-olC16H24O3[α]D25=-9.6 (c 0.80, CHCl3)Source of chirality: Jacobsen’s hydrolytic kinetic resolution, Sharpless asymmetric dihydroxylationAbsolute configuration: (4R,6R)