Studies directed toward the first total synthesis of acremodiol and acremonol

Studies directed toward the synthesis of acremodiol and acremonol resulted in the synthesis of two macrodiolides 1, 1a, and 2 besides 3. The attempted synthesis of 1 and 2 confirmed that the absolute stereochemistry defined in the earlier report is incorrect. Compound 1 was synthesized by RCM-mediated macrocyclization. Attempted synthesis of 2 failed to give good yields in the cyclization, and 1a and 2 were synthesized by the Yamaguchi macrolactonization method.

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tert-Butyl 4,5-dihydroxy-(E,4R,5R)-2-hexenoateC10H18O4[α]D = +10.5 (c 0.92, CHCl3)Source of chirality: asymmetric dihydroxylationAbsolute configuration: (4R,5R)

4-[3-(4-methoxybenzyloxy)-(3R)-4-pentenyl]-2,2-dimethyl-(4S)-1,3-dioxolaneC18H26O4[α]D = +33.0 (c 0.50, CHCl3)Source of chirality: d-mannitol & Jacobsen kinetic resolutionAbsolute configuration: (4S,3R)

5-(4-Methoxybenzyloxy)-(2S,5R)-6-heptene-1,2-diolC15H22O4[α]D = +41.3 (c 0.49, CHCl3)Source of chirality: d-mannitol & Jacobsen kinetic resolutionAbsolute configuration: (2S,5R)

1-[1-[3-Hydroxy-4-(4-methylphenylsulfonyloxy)-(3S)-butyl]-(1R)-2-propenyloxymethyl]-4-methoxybenzeneC22H28O6S[α]D = +39.7 (c 0.79, CHCl3)Source of chirality: d-mannitol & Jacobsen kinetic resolutionAbsolute configuration: (1R,3S)

(1R,2R)-1,2-Bis((R)-2,2-dimethyl-1,3-dioxolan-4-yl)ethane-1,2-diyl dibenzoateC26H30O8[α]D = −112.7 (c 3.37, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (1R,2R,1′R,1″R)

(4S,5R)-4-((R)-2,2-Dimethyl-1,3-dioxolan-4-yl)-2-(4-methoxyphenyl)-1,3-dioxan-5-olC16H22O6[α]D = +16.6 (c 0.54, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (4S,5R,4′R)

(2R,3S)-3-((R)-2,2-Dimethyl-1,3-dioxolan-4-yl)-3-(4-methoxy-benzyloxy)-propane-1,2-diolC16H24O6[α]D = +55.4 (c 0.11, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (2′R,3′S,4R)

(2R,3S,4R)-3-(4-Methoxybenzyloxy)pentane-1,2,4-triolC13H20O5[α]D = +8.7 (c 0.57, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (2R,3S,4R)

(4R,5R,E)-Ethyl 5-hydroxy-4-(4-methoxybenzyloxy)hex-2-enoateC16H22O5[α]D = −197.5 (c 1.2, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (4R,5R)

(4R,5R,E)-Ethyl 5-(tert-butyldimethylsilyloxy)-4-(4-methoxybenzyloxy)hex-2-enoateC22H36O5Si[α]D = −6.8 (c 0.91, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (4R,5R)

(R)-tert-Butyl(hex-5-en-2-yloxy)dimethylsilaneC14H28O3Si[α]D = −57.4 (c 0.76, CHCl3)Source of chirality: Jacobsen kinetic resolutionAbsolute configuration: (5R)

tert-Butyl 5-(tert-butyl dimethylsilyloxy)-4-hydroxy-(E,4R,5R)-2-hexenoateC16H32O4Si[α]D = −5.7 (c 0.69, CHCl3)Source of chirality: asymmetric dihydroxylationAbsolute configuration: (4R,5R)

(R,E)-Ethyl 6-(tert-butyldimethylsilyloxy)hept-2-enoateC14H28O3Si[α]D = −21.5 (c 1.6, CHCl3)Source of chirality: Jacobsen kinetic resolutionAbsolute configuration: (6R)

(3R,6R)-6-(tert-Butyldimethylsilyloxy)hept-1-en-3-olC13H28O2Si[α]D = −37.4 (c 0.18, CHCl3)Source of chirality: Jacobsen kinetic resolution & Sharpless epoxidationAbsolute configuration: (3R,6R)

(3S,6R)-(6-(tert-Butyl-dimethyl-silanyloxy)-hept-1-en-3-olC13H28O2Si[α]D = −22.5 (c 0.57, CHCl3)Source of chirality: Jacobsen kinetic resolution & Sharpless epoxidationAbsolute configuration: (3S,6R)

((2R,5R)-5-(Benzyloxy)hept-6-en-2-yloxy)(tert-butyl)dimethylsilaneC20H34O2Si[α]D = −23.6 (c 0.9, CHCl3)Source of chirality: Jacobsen kinetic resolution & Sharpless epoxidationAbsolute configuration: (2R,5R)

((2R,5S)-5-(Benzyloxy)hept-6-en-2-yloxy)(tert-butyl)dimethylsilaneC20H34O2Si[α]D = −69.9 (c 0.57, CHCl3)Source of chirality: Jacobsen kinetic resolution & Sharpless epoxidationAbsolute configuration: (2R,5S)

(4R,7R,E)-2-Tosylethyl 4-(benzyloxy)-7-(tert-butyldimethylsilyloxy)oct-2-enoateC30H44O6SSi[α]D = +22.8 (c 0.43, CHCl3)Source of chirality: Jacobsen kinetic resolution & Sharpless epoxidationAbsolute configuration: (4R,7R)

(4S,7R,E)-2-Tosylethyl 4-(benzyloxy)-7-(tert-butyldimethylsilyloxy)oct-2-enoateC30H44O6SSi[α]D = −61.2 (c 3.5, CHCl3)Source of chirality: Jacobsen kinetic resolution & Sharpless epoxidationAbsolute configuration: (4S,7R)

(4R,5R)-5-(tert-Butyl-dimethyl-silanyloxy)-4-(4-methoxy-benzyloxy)-hexanoic acidC22H38O5Si[α]D = +61.9 (c 1.53, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (4R,5R)

(tert-Butyl-(tert-butyldimethylsilyloxy)-4-(2-methoxyethoxymethoxy)-(E,4R,5R)-2-hexenoateC20H40O6Si[α]D = +5.8 (c 1.39, CHCl3)Source of chirality: asymmetric dihydroxylationAbsolute configuration: (4R,5R)

tert-Butyl 5-(tert-butyldimethylsilyloxy)-4-2-methoxyethoxymethoxy)-(4R,5R)-hexanoateC20H42O6Si[α]D = +21.7 (c 0.45, CHCl3)Source of chirality: asymmetric dihydroxylationAbsolute configuration: (4R,5R)

2,2-Dimethyl-4-[1-(4-methylphenylsulfonyloxy)-3-butenyl]-(4R)-1,3-dioxolaneC16H22O5S[α]D = +12.5 (c 1.5, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (4S,4′R)

4-(3-Butenyl)-2,2-dimethyl-(4S)-1,3-dioxolaneC9H16O2[α]D = +15.9 (c 2.85, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (4S)

4-[2,2-Dimethyl-(4S)-1,3-dioxolan-4-yl]-(2R)-butane-1,2-diolC9H18O4[α]D = +17.4 (c 0.63, CHCl3)Source of chirality: d-mannitol & Jacobsen kinetic resolutionAbsolute configuration: (2R,4′S)

4-2-[2-(4-Methoxyphenyl)-(4R)-1,3-dioxolan-4-yl]ethyl-2,2-dimethyl-(4S)-1,3-dioxolaneC17H24O5[α]D = +1.29 (c 0.31, CHCl3)Source of chirality: d-mannitol & Jacobsen kinetic resolutionAbsolute configuration: (4R,4′R)

4-[2,2-Dimethyl-(4S)-1,3-dioxolan-4-yl]-2-(4-methoxybenzyloxy)-(2R)-butan-1-olC17H26O5[α]D = +42.0 (c 0.50, CHCl3)Source of chirality: d-mannitol & Jacobsen kinetic resolutionAbsolute configuration: (2R,4′S)