Electronic supplementary material

Synthesis of the esters 7-methyloctyl 5-methylhexanoate, 7-methyloctyl octanoate, 7-methyloctyl

7-methyloctanoate, and 7-methyloctyl (Z)-4-decenoate:

General procedure: The esters were synthesized using a modified method of that described by

Tolasch et al. (2007). Commercially available chemicals were used without further purification.

5-Methylhexanoic acid, 5-methylhexyl bromide and (Z)-4-decen-1-ol were purchased from Alfa

Aesar. Tetrahydrofuran (THF), dimethyl sulfoxide (DMSO), dichloromethane (CH2Cl2) and

pyridine was dried and/or distilled prior to use. Preparative liquid chromatography was

performed on normal-phase silica gel (Merck 60, 230-400 mesh, 0.040-0.063 mm, 10-50 g/g of

product mixture) employing a gradient technique with an increasing concentration (0-100%) of

distilled diethyl ether in distilled pentane. Thin-layer chromatography (TLC) was performed to

monitor the progress of the reactions on silica gel plates (Merck 60, pre-coated aluminium foil),

using ethyl acetate (40%) in cyclohexane as an eluent, and plates were visualised by means of

ultraviolet irradiation and/or by spraying with vanillin in sulfuric acid and heating at 120°C.

Purity of the product was checked with GC analysis on a Varian 3300 GC instrument (Varian,

Palo Alto, CA, USA) using an EC-1 column (30 m x 0.32 mm ID, 0.25 μm film thickness

(Alltech, Deerfield, IL, USA)). Nitrogen was used as carrier gas. The column temperature was

maintained at 50°C for 5 min and then increased by 10°C/min to 300°C. Mass spectral analyses

were carried out on a Saturn 2000 GC/MS/MS instrument (Varian), coupled to a Varian 3800

GC instrument (Varian), using a CP-Sil 5 CB column (30 m x 0.32 mm ID, 0.25 μm film

thickness (Varian)). Helium was used as carrier gas at a flow rate of 1 ml/min. The same

temperature program was used as above. NMR spectra were recorded on a Bruker Avance 500

(500 MHz 1H, 125.8 MHz 13C) spectrometer (Bruker, Solna, Sweden) using CDCl3 as solvent

and TMS as internal standard.

7-Methyloctan-1-ol

NaH (2.7 g, 111 mmol) was added in portions to a solution of dimethyl malonate (14.7 g, 111

mmol) and THF (250 mL) at 0°C. The mixture was stirred for 10 min before drop-wise adding 5-

methylhexyl bromide (2.92 g, 16.3 mmol) in THF (50 mL). The reaction was set on reflux

overnight, and then quenched with NH4Cl (110 mL) and extracted with EtOAc (3 x 50 mL). The

combined organic layers were dried (MgSO4) and evaporated. Most of the excess of dimethyl

malonate was removed by distillation under reduced pressure, using a vigreux column. The crude

malonic ester was then purified by flash chromatography and checked by NMR. The crude

malonic ester (3.3 g, 14.3 mmol) in DMSO (6 mL) was added to a mixture of NaCl (0.84 g) and

H2O (1.0 mL) in DMSO (12 mL) and refluxed over night. The reaction was quenched with H2O

and extracted with EtOAc (2 x 25 mL). The combined organic layers were dried (MgSO4),

concentrated and after flash chromatography a pale yellow oil (2.0 g, 11.6 mmol) was obtained.

The obtained methyl ester was checked by NMR and used in the next step without further

purification. The product ester (1.7 g, 9.9 mmol) in THF (40 mL) was added drop-wise to a

stirred mixture of THF (40 mL) and LiAlH4 (0.76 g, 9.9 mmol) at 0°C. The reaction was allowed

to reach room temperature overnight. The reaction was quenched with NH4Cl and HCl (2 M) at

0°C and extracted with EtOAc (3 x 50 mL). The combined organic layers were washed with

brine (20 mL), dried (MgSO4) and the solvent evaporated. The pale oil was purified by bulb-to-

bulb distillation (130°C, 2 mbar) to yield the pure (GC) product alcohol (1.29 g, 8.96 mmol) as a

colourless oil in 55% from the bromide. The analytical data were accordingly to those reported in

the literature (Tolasch et al. 2007).

(Z)-4-decenoic acid

(Z)-4-decen-1-ol (3 g, 19.2 mmol) in acetone (160 mL) was stirred on an ice bath and Jones

reagent (28.8 mmol) was added at a temperature below 5°C. After 1 h the reaction was quenched

by adding water (8 mL). The reaction was extracted with Et2O (3 x 50 mL) and the combined

organic layers were washed with a water solution of Na2CO3 (3 x 30 mL), dried (Na2SO4) and the

solvent evaporated. The residue was purified by bulb-to-bulb distillation to yield the product acid

as an almost colourless oil (17 mmol, 89%). The analytical data were accordingly to those

reported in the literature (Tolasch et al. 2007).

7-metyloctanoic acid

The product acid was synthesized as above for (Z)-4-decenoic acid, but starting from 7-

methyloctan-1-ol. The analytical data were accordingly to those reported in the literature

(Tolasch et al. 2007).

7-Methyloctyl (Z)-4-decenoate

(Z)-4-decenoic acid (0.46 g, 2.71 mmol) in SOCl2 (2.2g, 1.4 mL, 18.9 mmol) was refluxed for 1

h. The excess SOCl2 was then removed by distillation and the obtained acid chloride was then

distilled bulb-to-bulb and immediately used in the next step. The acid chloride (0.51 g, 2.71

mmol) in CH2Cl2 (4 mL) was added drop-wise to a stirred solution of 7-methyloctan-1-ol (0.50 g,

2.7 mmol) in CH2Cl2 (4 mL) and pyridine (0.255 g, 3.0 mmol) under argon atmosphere. The

reaction was stirred overnight, during which it becomes slightly cloudy, and was then quenched

with water. The reaction was extracted with Et2O (3 x 20 mL) and the combined organic layers

were dried (MgSO4) and the solvent evaporated. The residue was purified by flash

chromatography to yield the product ester pure (GC) as a colourless oil (2.38 mmol, 88%). The

analytical data were accordingly to those reported in the literature (Tolasch et al. 2007).

7-Methyloctyl octanoate

The product ester was synthesized as above for 7-methyloctyl (Z)-4-decenoate but starting from

7-methyloctan-1-ol and octanoic acid. The analytical data were accordingly to those reported in

the literature (Tolasch et al. 2007).

7-Methyloctyl 7-methyloctanoate

The product ester was synthesized as above for 7-methyloctyl (Z)-4-decenoate, but starting from

7-methyloctan-1-ol and 7-metyloctanoic acid. The analytical data were accordingly to those

reported in the literature (Tolasch et al. 2007).

7-Methyloctyl 5-methylhexanoate

The product ester was synthesized as above for 7-methyloctyl (Z)-4-decenoate, but starting from

7-methyloctan-1-ol and 5-methylhexanoic acid. The analytical data were accordingly to those

reported in the literature (Tolasch et al. 2007).