Preparation and use of enantioenriched 2-aryl-propylsulfonylbenzene derivatives as valuable building blocks for the enantioselective synthesis of bisabolane sesquiterpenes

We have demonstrated that different enantioenriched 2-arylpropylsufonylbenzene derivatives are very useful building blocks for the synthesis of aromatic bisabolane sesquiterpenes. Their preparation and the exploitation of their chemical reactivity have been comprehensively investigated. Accordingly, the naturally occurring bisabolane sesquiterpenes (−)-curcuphenol, (−)-xanthorrhizol, (+)-glandulone A, (+)-curcudiol, (+)-turmerone and (+)-curcudiol-10-one were synthesized in high enantiomeric purity. It is worth noting that the compounds (+)-curcudiol-10-one and (+)-glandulone A were prepared in enantioenriched form for the first time. Through the proposed synthetic approaches, we were able to confirm both chemical structures and the absolute configurations previously assigned to the two aforementioned sesquiterpenes.

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(R)-2-Methoxy-4-methyl-1-(1-(phenylsulfonyl)propan-2-yl)benzeneC17H20O3See = 95%[α]D20 = +13.8 (c 2, CHCl3)Source of chirality: lipase-mediated resolutionAbsolute configuration: (2R)

(R)-1-Methyl-4-(1-(phenylsulfonyl)propan-2-yl)benzeneC16H18O2See = 96%[α]D20 = +7.8 (c 2.1, CHCl3)Source of chirality: lipase-mediated resolutionAbsolute configuration: (2R)

(S)-2-Methoxy-1-methyl-4-(1-(phenylsulfonyl)propan-2-yl)benzeneC17H20O3See = 95%[α]D20 = −2.1 (c 3.2, CHCl3)Source of chirality: lipase-mediated resolutionAbsolute configuration: (2S)

(R)-1,4-Dimethoxy-2-methyl-5-(1-(phenylsulfonyl)propan-2-yl)benzeneC18H22O4See = 94%[α]D20 = +5.4 (c 2.5, CHCl3)Source of chirality: lipase-mediated resolutionAbsolute configuration: (2R)

(S)-2-Methyl-6-p-tolylhept-2-en-4-oneC15H20Oee = 96%[α]D20 = +71.0 (c 3, hexane)Source of chirality: lipase-mediated resolutionAbsolute configuration: (6S)

(R)-2-Methoxy-4-methyl-1-(6-methylhept-5-en-2-yl)benzeneC16H24Oee = 98%[α]D20 = −7.5 (c 2, CHCl3)Source of chirality: lipase-mediated resolutionAbsolute configuration: (2R)

(R)-5-Methyl-2-(6-methylhept-5-en-2-yl)phenolC15H22Oee = 98%[α]D20 = −23.2 (c 2.9, CHCl3)Source of chirality: lipase-mediated resolutionAbsolute configuration: (2R)

(S)-6-(2-Methoxy-4-methylphenyl)-2-methylheptan-2-olC16H26O2ee = 95%[α]D20 = +7.5 (c 2, CHCl3)Source of chirality: lipase-mediated resolutionAbsolute configuration: (6S)

(S)-2-(6-Hydroxy-6-methylheptan-2-yl)-5-methylphenolC15H24O2ee = 95%[α]D20 = +11.3 (c 2.9, CHCl3)Source of chirality: lipase-mediated resolutionAbsolute configuration: (2S)

(S)-2-Hydroxy-6-(2-hydroxy-4-methylphenyl)-2-methylheptan-3-oneC15H22O3ee = 95%[α]D20 = +19.1 (c 2.2, CHCl3)Source of chirality: lipase-mediated resolutionAbsolute configuration: (6S)

(R)-2-Methoxy-1-methyl-4-(6-methylhept-5-en-2-yl)benzeneC16H24Oee = 95%[α]D20 = −41.9 (c 2.2, CHCl3)Source of chirality: lipase-mediated resolutionAbsolute configuration: (2R)

(R)-2-Methyl-5-(6-methylhept-5-en-2-yl)phenolC15H22Oee = 95%[α]D20 = −41.3 (c 2.5, acetone)Source of chirality: lipase-mediated resolutionAbsolute configuration: (2R)

(S,E)-tert-Butyl(6-(2,5-dimethoxy-4-methylphenyl)-2-methylhept-2-enyloxy)diphenylsilaneC33H44O3Siee = 94%[α]D20 = +16.7 (c 2.2, CHCl3)Source of chirality: lipase-mediated resolutionAbsolute configuration: (6S)

(S,E)-6-(2,5-Dimethoxy-4-methylphenyl)-2-methylhept-2-en-1-olC18H28O4ee = 94%[α]D20 = +31.6 (c 3, CHCl3)Source of chirality: lipase-mediated resolutionAbsolute configuration: (6S)

(S,E)-2-Methyl-6-(4-methyl-3,6-dioxocyclohexa-1,4-dienyl)hept-2-enalC15H18O3ee = 94%[α]D20 = +47.1 (c 3.2, MeOH)Source of chirality: lipase-mediated resolutionAbsolute configuration: (6S)