Stereoselective total synthesis of simplactone A

The efficient and simple stereoselective approach toward the total synthesis of simplactone A is described. The key features of this synthetic strategy include stereoselective C-ethylation, selective triol protection, and Wittig olefination for the formation of the six-membered ring.

Figure optionsDownload as PowerPoint slide

Dimethyl (2R,3S)-2-ethyl-3-hydroxybutanedioateC6H10O5[α]D20=+9.3 (c 1.1, CHCl3)Source of chirality: (S)-malic acidAbsolute configuration: (2R,3S)

(2S,3S)-3-Ethylbutane-1,2,4-triolC6H14O3[α]D25=+19.5 (c 1.1, CHCl3)Source of chirality: (S)-malic acidAbsolute configuration: (2S,3S)

[(2S,4S,5S)-5-Ethyl-2-(4-methoxyphenyl)-1,3-dioxan-4-yl]methanolC14H20O4[α]D25=+31.5 (c 1.1, CHCl3)Source of chirality: (S)-malic acidAbsolute configuration: (4S,5S)

(2S,4R,5S)-5-Ethyl-2-(4-methoxyphenyl)-4-vinyl-1,3-dioxaneC15H20O3[α]D25=+15.5 (c 1.1, CHCl3)Source of chirality: (S)-malic acidAbsolute configuration: (4R,5S)

2-[(2S,4R,5S)-5-Ethyl-2-(4-methoxyphenyl)-1,3-dioxan-4-yl]-1-ethanolC15H22O4[α]D25=+81.5 (c 1.1, CHCl3)Source of chirality: (S)-malic acidAbsolute configuration: (4R,5S)

2-[(2S,4R,5S)-5-Ethyl-2-(4-methoxyphenyl)-1,3-dioxan-4-yl]acetic acidC15H20O5[α]D25=+55.5 (c 1.1, CHCl3)Source of chirality: (S)-malic acidAbsolute configuration: (4R,5S)

Methyl 2-[(2S,4R,5S)-5-ethyl-2-(4-methoxyphenyl)-1,3-dioxan-4-yl]acetateC16H22O5[α]D25=+82.0 (c 1.1, CHCl3)Source of chirality: (S)-malic acidAbsolute configuration: (4R,5S)

(4R,5S)-5-Ethyl-4-hydroxytetrahydro-2H-2-pyranoneC7H12O3[α]D22=+22.9 (c 1.1, CHCl3)Source of chirality: (S)-malic acidAbsolute configuration: (4R,5S)