Enantioselective total synthesis of both the stereoisomers of dihydrokawain-5-ol

The enantioselective synthesis of both the stereoisomers of dihydrokawain-5-ol is described. The key features of the synthetic strategy include (a) Sharpless asymmetric dihydroxylation, (b) Wittig olefination, and (c) formation of β-keto ester to access the highly enantiomerically pure kavalactones.

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5-Phenylpentane-1,2,3-triolC11H16O3[α]D23.5=+20.2 (c 1.8, CHCl3)Source of chirality: Sharpless asymmetric dihydroxylation

(5R,6R)-2-(4-Methoxyphenyl)-4-phenethyl-[1,3]dioxan-5-olC19H22O4[α]D23.5=+75.9 (c 2.0, CHCl3)Source of chirality: Sharpless asymmetric dihydroxylation

(5R,6R)-5-Benzyloxy-2-(4-methoxyphenyl)-6-phenethyl-[1,3]dioxaneC26H28O4[α]D26=+57.75 (c 1.0, CHCl3)Source of chirality: Sharpless asymmetric dihydroxylation

(2R,3R)-2-Benzyloxy-3-(4-methoxybenzyloxy)-5-phenylpentan-1-olC26H30O4[α]D23.5=+25.4 (c 1.0, CHCl3)Source of chirality: Sharpless asymmetric dihydroxylation

(4S,5R)-4-Benzyloxy-(4-methoxybenzyloxy)-3-oxo-7-phenylheptanoicacidethylesterC30H34O6[α]D23.5=-21.0 (c 1.2, CHCl3)Source of chirality: Sharpless asymmetric dihydroxylation

(4S,5R)-4-Benzyloxy-5-hydroxy-3-oxo-7-pheny-heptanoicacidethylesterC22H26O5[α]D23.5=-40.6 (c 1.0, CHCl3)Source of chirality: Sharpless asymmetric dihydroxylation

(5S,6R)-5-Benzyloxy-4-methoxy-6-phenethyl-5,6-dihydro-2H-pyran-2-oneC21H22O4[α]D26=-120.5 (c 4.5, CHCl3)Source of chirality: Sharpless asymmetric dihydroxylation

(5S,6R)-5-Hydroxy-4-methoxy-6-phenethyl-5,6-dihydro-2H-pyran-2-oneC14H16O4[α]D26=-62.5 (c 2.0, CHCl3)Source of chirality: Sharpless asymmetric dihydroxylation

(5R,6S)-5-Hydroxy-4-methoxy-6-phenethyl-5,6-dihydro-2H-pyran-2-oneC14H16O4[α]D23.5=+61.0 (c 2.0, CHCl3)Source of chirality: Sharpless asymmetric dihydroxylation