An efficient aldol-based approach for the synthesis of dihydrokawain-5-ol

An efficient and simple aldol-based convergent approach toward the total synthesis of (+)- and (−)-dihydrokawain-5-ol is described. The key features of this synthetic strategy include Evans’ aldol reaction and an ethyl acetate addition reaction for the formation of the six-membered ring.

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(4S)-4-Benzyl-3-[(2S,3R)-2-(benzyloxy)-3-hydroxy-5-phenylpentanoyl]-1,3-oxazolan-2-oneC28H29NO5[α]D25=+70.5 (c 1.5, CHCl3)Source of chirality: Evans’ asymmetric aldolAbsolute configuration:(2S,3R)

(2S,3R)-2-(Benzyloxy)-3-hydroxy-N-methoxy-N-methyl-5-phenylpentanamideC20H25NO4[α]D25=-13.5 (c 1.1, CHCl3)Source of chirality: Evans’ asymmetric aldolAbsolute configuration:(2S,3R)

(2S,3R)-2-(Benzyloxy)-3-(tert-butyldimethylsilyloxy)-N-methoxy-N-methyl-5-phenylpentanamideC26H39NO4Si[α]D25=-4.4 (c 1.4, CHCl3)Source of chirality: Evans’ asymmetric aldolAbsolute configuration: (2S,3R)

Ethyl(4R,5R)-4-(benzyloxy)-5-[1-(tert-butyl)-1,1-dimethylsilyl]oxy-3-hydroxy-7-phenylheptanoateC28H42O5Si[α]D25=+33.4 (c 1.1, CHCl3)Source of chirality: Evans’ asymmetric aldolAbsolute configuration: (4R,5R)

Ethyl(4S,5R)-4-(benzyloxy)-5-[1-(tert-butyl)-1,1-dimethylsilyl]oxy-3-oxo-7-phenylheptanoateC28H40O5Si[α]D25=+6.8 (c 1.1, CHCl3)Source of chirality: Evans’ asymmetric aldolAbsolute configuration: (4S,5R)

(5S,6R)-5-(Benzyloxy)-4-methoxy-6-phenethyl-5,6-dihydro-2H-2-pyranoneC21H22O4[α]D25=-118.9 (c 1.5, CHCl3)Source of chirality: Evans’ asymmetric aldolAbsolute configuration: (5S,6R)

(5S,6R)-5-Hydroxy-4-methoxy-6-phenethyl-5,6-dihydro-2H-2-pyranoneC14H16O4[α]D25=-63.2 (c 1.1, CHCl3)Source of chirality: Evans’ asymmetric aldolAbsolute configuration: (5S,6R)