Stereoselective synthesis of (2S,3S,7S)-3,7-dimethylpentadecan-2-ol and its propionate, the sex pheromones of pine sawflies

The stereoselective synthesis of (2S,3S,7S)-3,7-dimethylpentadecan-2-ol (diprionol) and its propionate, the sex pheromones of pine sawflies (Neodiprion sp. and other), in high enantiomeric purity was achieved from (1R,3S)-2,2-dichloro-3-methylcyclopropanecarboxylic acid. The carbon skeleton of diprionol was formed via copper-catalyzed cross-coupling reactions and diastereoselective methylation of the intermediate chiral α-methylbranched aldehyde with MeTi(Oi-Pr)3 in the presence of [(R,R)-TADDOL]Ti(Oi-Pr)2. The latter transformation leads to a syn-adduct with high stereoselectivity, which depends on the presence and configuration of the α-stereogenic center in the aldehyde. The diastereomeric purity of (2S,3S,7S)-diprionol can be substantially increased via crystallization of its 3,5-dinitrobenzoate.

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(S)-3-Methyl-4,4-dimethoxybutan-1-olC7H16O3[α]D20=-5.6 (c 3.2, Et2O)Source of chirality: (1R,3S)-(+)-2,2-dichloro-3-methylcyclopropanecarboxylic acidAbsolute configuration: (3S)

(S)-4-Bromo-2-methyl-1,1-dimethoxybutaneC7H15BrO2[α]D20=-14.5 (с 5.0, Et2O)Source of chirality: (1R,3S)-(+)-2,2-dichloro-3-methylcyclopropanecarboxylic acidAbsolute configuration: (2S)

(S)-2-Methyl-1,1-dimethoxydecaneC13H28O2[α]D20=-13.5 (с 4.8, hexane)Source of chirality: (1R,3S)-(+)-2,2-dichloro-3-methylcyclopropanecarboxylic acidAbsolute configuration: (2S)

(S)-2-MethyldecanalC11H22Oee >99%[α]D20=+13.5 (с 3.6, Et2O)Source of chirality: (1R,3S)-(+)-2,2-dichloro-3-methylcyclopropanecarboxylic acidAbsolute configuration: (2S)

(S)-2-Methyldecan-1-olC11H24Oee >99%[α]D20=-10.0, (с 1.2, MeOH)Source of chirality: (1R,3S)-(+)-2,2-dichloro-3-methylcyclopropanecarboxylic acidAbsolute configuration: (2S)

(2S,6S)-2,6-Dimethyl-1,1-dimethoxytetradecaneC18H38O2[α]D20=-10.1 (с 1.6, hexane)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,6S)

(2S,3S,7S)-3,7-Dimethylpentadec-2-yl-3,5-dinitrobenzoateC24H38N2O6[α]D20=+19.2 (с 1.2, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3S,7S)

(2S,3S,7S)-3,7-Dimethylpentadecan-2-olC17H36Ode and ee >99%[α]D20=-11.3 (с 3.2, hexane)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3S,7S)

(2S,3S,7S)-3,7-Dimethylpentadec-2-yl propionateC20H40O2[α]D20=-5.6 (с 0.6, hexane)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3S,7S)