Enantioselective synthesis of the essential oil and pheromonal component ar-himachalene by a chiral pool and chirality induction approach

The enantioselective synthesis of both isomers of ar-himachalene has been achieved starting from enantiomerically pure citronellal and p-methyl α-methyl styrene as an application of a chiral pool and chirality induction approach, respectively. The key reactions involved in the synthesis include the Sharpless asymmetric dihydroxylation for the induction of chirality at benzylic carbon bearing the methyl group and the use of a hypervalent iodine reagent or trimethylsilyldiazomethane (TMSCHN2) for the six to seven membered ring expansion.

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(R)-2-(p-Tolyl)propane-1,2-diolC10H14O2ee = 99%[α]D25=-10.7 (c 1, CHCl3)Source of chirality: Sharpless asymmetric dihydroxylationAbsolute configuration: (R)

(R)-2-(4-Methylphenyl)propanolC10H13Oee = 97.5%[α]D25=+17.4 (c 1, CHCl3)Source of chirality: Sharpless asymmetric dihydroxylationAbsolute configuration: (R)

(S)-4-(p-Tolyl)pentanoic acidC12H16O2ee = 92%[α]D25=+14.2 (c 1, CHCl3)Source of chirality: Sharpless asymmetric dihydroxylationAbsolute configuration: (S)

(S)-4,7-Dimethyl-3,4-dihydronaphthalen-1(2H)-oneC12H14Oee = 96%[α]D20=-10.0 (c 1, CHCl3)Source of chirality: Sharpless asymmetric dihydroxylationAbsolute configuration: (S)

(S)-1,6-Dimethyl-4-methylene-1,2,3,4-tetrahydronaphthaleneC13H16ee = 92.5%[α]D25=+3.2 (c 1, CHCl3)Source of chirality: Sharpless asymmetric dihydroxylationAbsolute configuration: (S)

(S)-3,9-Dimethyl-8,9-dihydro-5H-benzo[7]annulen-6(7H)-oneC13H16Oee = 93%[α]D25=+69.2 (c 1, CHCl3)Source of chirality: Sharpless asymmetric dihydroxylationAbsolute configuration: (S)

(S)-3,5,5,9-Tetramethyl-8,9-dihydro-5H-benzo[7]annulen-6(7H)-oneC15H20Oee = 93%[α]D25=+32.1 (c 1, CHCl3)Source of chirality: Sharpless asymmetric dihydroxylationAbsolute configuration: (S)

(S)-2,5,9,9-Tetramethyl-6,7,8,9-tetrahydro-5H-benzo[7]annuleneC15H22ee = 94%[α]D20=+2.9 (c 1, CHCl3)Source of chirality: Sharpless asymmetric dihydroxylationAbsolute configuration: (S)