An enantiospecific total synthesis of (−)-patchouli alcohol

An enantiospecific total synthesis of patchouli alcohol, starting from the readily available monoterpene (R)-carvone, has been accomplished. A tandem double Michael reaction–alkylation sequence and single electron mediated 6-endo trig cyclisation reaction have been employed as key steps.

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(1S,2R,4S,8S)-8-Isopropenyl-4,6,6-trimethyl-5-oxobicyclo[2.2.2]octane-2-carboxylic acid methyl esterC16H24O3[α]D23=-96.6 (c 3.0, CHCl3).Source of chirality: (R)-carvoneAbsolute configuration: (1S,2R,4S,8S)

(1S,4R,6S)-6-Isopropenyl-1,3,3-trimethylbicyclo[2.2.2]octan-2-oneC14H22O[α]D24=-51.2 (c 4.8, CHCl3).Source of chirality: (R)-carvoneAbsolute configuration: (1S,4R,6S)

(1S,4R,6R)-6-Acetyl-1,3,3-trimethylbicyclo[2.2.2]octan-2-oneC13H20O2[α]D23=-44.0 (c 5.2, CHCl3).Source of chirality: (R)-carvoneAbsolute configuration: (1S,4R,6R)

(1R,3R,7S,8S)-2,2,6,8-Tetramethyltricyclo[5.3.1.03,8]undec-5-en-3-olC16H27O[α]D24=+42.3 (c 1.7, CHCl3).Source of chirality: (R)-carvoneAbsolute configuration: (1R,3R,7S,8S)

(1R,3R,6S,7S,8S)-2,2,6,8-Tetramethyltricyclo[5.3.1.03,8]undecan-3-olC16H29O[α]D25=-121.3 (c 2.3, CHCl3).Source of chirality: (R)-carvoneAbsolute configuration: (1R,3R,6S,7S,8S)