Enantioselective synthesis of α-benzyloxy-ω-alkenals: application to the synthesis of (+)-exo-brevicomin, (+)-iso-exo-brevicomin, and (−)-isolaurepan

The enantioselective synthesis of α-benzyloxy aldehydes containing a terminal alkene was carried out from chiral pool l-(+)-tartaric acid by employing the stereoselective reduction of a 1,4-diketone as the key step. The synthetic utility of these aldehydes was demonstrated in the synthesis of pine beetle pheromones (+)-exo-brevicomin, (+)-iso-exo-brevicomin and a formal synthesis of 2,7-cis-disubstituted oxepane (−)-isolaurepan.

Figure optionsDownload as PowerPoint slide

(4R,5R)-4,5-Bis(pent-4-enoyl)-2,2-dimethyl-1,3-dioxolaneC15H22O4[α]D = +10.5 (c 1.8, CHCl3)Source of chirality: l-(+)-tartaric acidAbsolute configuration: (4R,5R)

(4R,5R)-4,5-Bis(hex-5-enoyl)-2,2-dimethyl-1,3-dioxolaneC17H26O4[α]D = +11.6 (c 1.2, CHCl3)Source of chirality: l-(+)-tartaric acidAbsolute configuration: (4R,5R)

(4R,5R)-4,5-Bis(hept-6-enoyl)-2,2-dimethyl-1,3-dioxolaneC19H30O4[α]D = +10.0 (c 1.0, CHCl3)Source of chirality: l-(+)-tartaric acidAbsolute configuration: (4R,5R)

(4S,5S)-4,5-Bis((R)-1-hydroxypent-4-enyl)-2,2-dimethyl-1,3-dioxolaneC15H26O4[α]D = −7.8 (c 2.8, CHCl3)Source of chirality: l-(+)-tartaric acidAbsolute configuration: (4S,5S)

(4S,5S)-4,5-Bis((R)-1-hydroxyhex-5-enyl)-2,2-dimethyl-1,3-dioxolaneC17H30O4[α]D = −7.5 (c 1.1, CHCl3)Source of chirality: l-(+)-tartaric acidAbsolute configuration: (4S,5S)

(4S,5S)-4,5-Bis((R)-1-hydroxyhept-6-enyl)-2,2-dimethyl-1,3-dioxolaneC19H34O4[α]D = −8.6 (c 3.0, CHCl3)Source of chirality: l-(+)-tartaric acidAbsolute configuration: (4S,5S)

(5R,6R,7R,8R)-5,8-Bis(benzyloxy)dodeca-1,11-diene-6,7-diolC26H34O4[α]D = −24.4 (c 1.8, CHCl3)Source of chirality: l-(+)-tartaric acidAbsolute configuration: (5R,6R,7R,8R)

(6R,7R,8R,9R)-6,9-Bis(benzyloxy)tetradeca-1,13-diene-7,8-diolC28H38O4[α]D = −25.8 (c 2.1, CHCl3)Source of chirality: l-(+)-tartaric acidAbsolute configuration: (6R,7R,8R,9R)

(7R,8R,9R,10R)-7,10-Bis(benzyloxy)hexadeca-1,15-diene-8,9-diolC30H42O4[α]D = −27.7 (c 2.7, CHCl3)Source of chirality: l-(+)-tartaric acidAbsolute configuration: (7R,8R,9R,10R)

(R)-2-(Benzyloxy)hex-5-en-1-olC13H18O2[α]D = −10.8 (c 3.5, CHCl3)Source of chirality: l-(+)-tartaric acidAbsolute configuration: (2R)

(R)-2-(Benzyloxy)hept-6-en-1-olC14H20O2[α]D = −12.2 (c 1.8, CHCl3)Source of chirality: l-(+)-tartaric acidAbsolute configuration: (2R)

(R)-2-(Benzyloxy)oct-7-en-1-olC15H22O2[α]D = −14.7 (c 1.9, CHCl3)Source of chirality: l-(+)-tartaric acidAbsolute configuration: (2R)

(+)-exo-Brevicomin: (1R,5S,7R)-7-ethyl-5-methyl-6,8-dioxabicyclo[3.2.1]octaneC9H16O2[α]D = +66.6 (c 0.3, Et2O)Source of chirality: l-(+)-tartaric acidAbsolute configuration: (1R,5S,7R)

(2R,3R)-3-(Benzyloxy)oct-7-en-2-olC15H22O2[α]D = −24.3 (c 1.1, CHCl3)Source of chirality: l-(+)-tartaric acidAbsolute configuration: (2R,3R)

(7R,8R)-7,8-Bis(benzyloxy)nonan-3-oneC22H30O3[α]D = +9.1 (c 3.2, CHCl3)Source of chirality: l-(+)-tartaric acidAbsolute configuration: (7R,8R)

iso-exo-Brevicomin: (1R,5S,7R)-5-ethyl-7-methyl-6,8-dioxabicyclo[3.2.1]octaneC9H16O2[α]D = +54.0 (c 0.5, CHCl3)Source of chirality: l-(+)-tartaric acidAbsolute configuration: (1R,5S,7R)

(R)-2-(Benzyloxy)-1-(methoxymethoxy)tridecan-7-oneC22H36O4[α]D = +13.7 (c 1.6, CHCl3)Source of chirality: l-(+)-tartaric acidAbsolute configuration: (2R)

(R)-2-(Hydroxy)-1-(methoxymethoxy)tridecan-7-oneC15H30O4[α]D = +15.0 (c 1.4, CHCl3)Source of chirality: l-(+)-tartaric acidAbsolute configuration: (2R)

(2R,7R)-7-Hexyl-2-(hydroxymethyl)oxepaneC13H26O5[α]D = +6.6 (c 1.8, MeOH)Source of chirality: l-(+)-tartaric acidAbsolute configuration: (2R,7R)