Supporting Information. Copyright Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, 2008

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1 Supporting Information Copyright Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, 2008

2 Supporting Information General: 1 H NMR and 13 C spectra were recorded on a Varian rcury 600 or a Bruker RX 500 spectrometer. NMR spectra were calibrated to the solvent signal of CCl 3 (7.26 ppm and ppm). The following abbreviations were used to explain multiplicities: s = singlet, d = doublet, t = triplet, q = quartet, quint = quintet, sext = sextet, sept = septet, m = multiplet, br = broad. GC-MS(EI) were measured on a Hewlett-Packard 6890 Series gas chromatograph connected to a Hewlett-Packard 5973 series mass spectrometer; column: H&W 19091σ-102 HP-5MS capillary: 25.0 m 201 μm 0.33 μm nominal. LC-MS was performed on a 1100 series from Hewlett-Packard connected to a Finnigan LCQ ESI-Spectrometer; column: VP 50 / 10 Nucleosil C18PPN-column (Macherey-Nagel); gradient: 90 / 10 (v / v) H 2 / acetonitrile (0.1% formic acid) to 10 / 90 (v / v) in 30 min, flow 1.00 ml / min. Preparative HPLC was conducted by using a Agilent 1100 Series; column: VP 125 / 21 NUCLEUR C18 Gravity, 5 μ (Macherey-Nagel); gradient: 60 / 40 (v / v) H 2 / acetonitrile (no acid!) to 100% acetonitrile in 29 min, flow 10 ml / min. High resolution mass spectra (HR-MS) were measured on a finnigan MAT 8200 spectrometer. IR spectra were measured on a Bruker Vector 22 spectrometer with a diffuse reflectance head A527 from Spectra Tech. UV spectra were measured on a Perkin Elmer Cary 50 spectrometer. HPLC was measured on Hewlett-Packard 1100 HPLC. The optical rotation was determined with Perkin Elmer Polarimeter 241. Chiral GC was measured on a Agilent Technologies 6890N; column: Lipodex-E (25 m, mm); 85 C isotherm. TLC was performed on rck silica gel 60F254 aluminium sheets using UV as a visualizing agent and a 0.5% aqueous potassium permanganate solution or an ethanolic solution of phosphomolybdic acid and heat as developing agents. For flash chromatography silica gel (40-60 µm) from rck was used. Wang resin (1.1 mmol g 1, 1% VB, mesh) was purchased from Novabiochem. All reactions were performed under an argon atmosphere with freshly distilled and dried solvents. All solvents were distilled using standard procedures. Unless otherwise noted, reagents were obtained from Aldrich, Acros, Fluka, Lancaster and Strem and used without further purification. S1

3 (S)-1-(Benzyloxy)-pent-4-en-2-ol (15b): (S)-2-((Benzyloxy)methyl)oxirane [1] (41b) (3.00 g, 18.3 mmol, 1.00 eq) was dissolved in 30 ml dry THF and the solution was cooled to -40 C. Copper(I) iodide (174 mg, 0.91 mmol, 0.05 eq) was added and the suspension was stirred for 15 min. A 1 M solution of vinylmagnesium bromide (23.8 ml, 23.8 mmol, 1.30 eq) was added over a period of 20 min at 40 C. After further 20 min the reaction was quenched with saturated, aqueous ammonium chloride solution (30 ml). The biphasic mixture was separated, the aqueous layer was extracted with diethylether (3 100 ml), the combined organic layers were washed with brine (100 ml), dried (MgS 4 ) and concentrated. The residue was purified by column chromatography (cyclohexane / EtAc = 6 / 1) to give 3.15 g (R)-1- (benzyloxy)pent-4-en-2-ol (15b) (16.4 mmol, 90%) as colorless liquid. R f = 0.21 (cyclohexane / EtAc = 6 / 1); purity 98%; [ α ] 20 = 2.8 (c = 2.36, CHCl 3 ) (lit. [2] : 2.8 ); ee 98% (determined via NMR analysis of the corresponding Mosher ester [3] ); 1 H-NMR (500.1 MHz, CCl 3 ): δ (ppm) = (m, 5H, 5 C ar H), 5.81 (ddt, 3 J = 17.2 Hz, 3 J = 10.1 Hz, 3 J = 7.1 Hz, 1H, CH=CH 2 ), (m, 2H, CH=CH 2 ), 4.54 (s, 2H, PhCH 2 ), 3.86 (ddd, 3 J = 13.8 Hz, 3 J = 6.4 Hz, 3 J = 3.5 Hz, 1H, CHH), 3.50 (dd, 2 J = 9.5 Hz, 3 J = 3.5 Hz, 1H, CH 2 Bn), 3.36 (dd, 2 J = 9.5 Hz, 3 J = 7.3 Hz, 1H, CH 2 Bn), 2.39 (br, 1H, H), (m, 2H, CH 2 CH=CH 2 ); 13 C-NMR (125.8 MHz, CCl 3 ): δ (ppm) = (s, C ar ), (d, CH=CH 2 ), (d, C ar ), (d, C ar ), (d, C ar ), (t, CH=CH 2 ), 74.0 (t, PhCH 2 ), 73.5 (t, CH 2 Bn), 69.8 (d, CHH), 38.0 (t, CH 2 CH=CH 2 ); GC-MS(EI): t R = 5.17 min; m / z (rel. Int. [%]): 192 (2), 174 (5), 151 (6), 121 (6), 107 (18), 101 (1), 91 (100), 77 (9), 65 (24). The (R)-enantiomer 15a was obtained starting from (R)-2-((benzyloxy)methyl)oxirane (41a). [ α ] 20 = 2.5 (c = 2.85, CHCl 3 ). (R,E)-1-Phenylhept-5-en-3-ol (16a) [4a] : A solution of crotylmagnesium chloride in THF (0.8 M, 45.8 ml, 36.6 mmol, 1.27 eq), which had been prepared freshly from distilled crotylchloride and magnesium, was added dropwise to an ice-cold solution of 4.46 g L-( )- menthone (28.9 mmol, 1.00 eq), that had been prepared freshly by PCC oxidation of L-( )- menthol, in 40 ml dry THF. After 2 h at 0 C the reaction was quenched with saturated, aqueous ammonium chloride solution (40 ml) and water (40 ml). The biphasic mixture was separated, the aqueous layer was extracted with diethylether (3 50 ml), the combined organic layers were washed with brine (50 ml), dried (MgS 4 ) and concentrated. The residue was purified by column chromatography (cyclohexane / Et 2 = 99 / 1) to give 3.85 g (1R,2S)- S2

4 1-((R)-but-3-en-2-yl)-2-isopropylcyclohexanol (18.3 mmol, 63%) as colorless liquid. R f = 0.10 (cyclohexane / Et 2 = 98 / 2); purity 98%; [ α ] 20 = 26.3 (c = 1.63, CHCl 3 ) (lit. [4b] : 27.4 ); 1 H-NMR (500.1 MHz, CCl 3 ): δ (ppm) = 5.87 (ddd, 3 J = 16.8 Hz, 3 J = 10.5 Hz, 3 J = 8.2 Hz, 1H, CH 2 =CH), (m, 2H, CH 2 =CH), 2.59 (quint, 3 J = 7.5 Hz, 1H, CH 2 =CHCH), 2.08 (sept, 3 J = 6.8 Hz, 1H, CH 2 ), (m, 2H), (m, 2H), 1.43 (br, 1H, H), (m, 2H), (m, 1H), 0.98 (t, 3 J = 12.3 Hz, 1H), 0.96 (d, 3 J = 7.0 Hz, 3H, CH 2 =CHCH), 0.92 (d, 3 J = 3.0 Hz, 3H, CH 2 ), 0.90 (d, 3 J = 3.0 Hz, 3H, CH 2 ), 0.85 (d, 3 J = 6.5 Hz, 3H, CH 2 CHCH 2 ); S3 13 C-NMR (125.8 MHz, CCl 3 ): δ (ppm) = (d, CH=CH 2 ), (t, CH=CH 2 ), 76.3 (s, CH), 46.1 (d, CHCH 2 ), 45.4 (d, CH 2 =CHCH), 41.7 (t, ), 35.4 (t), 27.7 (d, CH 2 CHCH 2 ), 25.1 (d, CH 2 ), 23.5 (q, ), 22.7 (q, ), 20.7 (t), 18.1 (q, ), 14.8 (q, ); GC-MS(EI): t R = 4.87 min; m / z (rel. Int. [%]): 210 (1), 195 (1), 155 (86), 137 (51), 125 (10), 111 (15), 95 (63), 81 (100), 69 (67). The (1S,2R)-1-((S)-but-3-en-2-yl)-2-isopropylcyclohexanol was obtained starting from R-(+)- menthone [ α ] 20 = 26.0 (c = 1.79, CHCl 3 ). Freshly distilled 3-phenylpropanal (33) (3.35 g, 25.0 mmol, 1.00 eq) and 5.78 g (1R,2S)-1- ((R)-but-3-en-2-yl)-2-isopropylcyclohexanol (27.5 mmol, 1.10 eq) were dissolved in 25 ml dry dichloromethane and 476 mg p-toluenesulfonic acid (2.50 mmol, 0.10 eq) was added at room temperature. After 24 h stirring 1.0 g solid sodium bicarbonate was added and stirring was continued for 60 min. The suspension was filtered and concentrated. Purification by column chromatography (cyclohexane / Et 2 = 9 / 1) yielded 4.12 g (R,E)-1-phenylhept-5-en- 3-ol (16a) (21.6 mmol, 87%) as colorless liquid. R f = 0.35 (pentane / Et 2 = 1 / 1); purity 98%; [ α ] 20 = 14.1 (c = 2.09, CHCl 3 ) (lit. [4b] : 15.1 ); ee 98% (determined via NMR analysis of the corresponding Mosher ester); 1 H-NMR (500.1 MHz, CCl 3 ): δ (ppm) = (m, 5H, 5 C ar H), (m, 1H, CH=CH), (m, 1H, CH=CH), (m, 1H, CHH), 2.82 (dt, 2 J = 14.5 Hz, 3 J = 7.2 Hz, 1H, PhCH 2 ), 2.69 (dt, 2 J = 13.8 Hz, 3 J = 8.0 Hz, 1H, PhCH 2 ), (m, 1H, CH 2 CH=CH), 2.11 (dt, 2 J = 14.2 Hz, 3 J = 7.5 Hz, 1H, CH 2 CH=CH), (m, 2H, PhCH 2 CH 2 ), 1.71 (d, 3 J = 6.2 Hz, 3H, ), 1.44 (br, 1H, H); 13 C-NMR (125.8 MHz, CCl 3 ): δ (ppm) = (s, C ar ), (d), (d), (d), (d), (d), 70.2 (d, CHH), 40.8 (t, PhCH 2 CH 2 ), 38.4 (t, CH 2 CH=CH), 32.1 (t, PhCH 2 ), 18.0 (q, ); GC-MS(EI): t R = 5.35 min; m / z (rel. Int. [%]): 172 (2), 134 (68), 117 (24), 105 (17), 91 (100), 78 (18), 65 (26), 55 (17).

5 The (S)-enantiomer 16b was obtained starting from (1S,2R)-1-((S)-but-3-en-2-yl)-2- isopropylcyclohexanol. [ α ] 20 = 16.3 (c = 2.08, CHCl 3 ); ee 98% (determined via NMR analysis of the corresponding Mosher ester). (S,E)-1-(Benzyloxy)hept-5-en-3-ol (17a): In a similar manner 3.03 g (S,E)-1- (benzyloxy)hept-5-en-3-ol (17a) (13.7 mmol, 75%) was prepared from 2.99 g freshly prepared 3-(benzyloxy)propanal [5] (34) (18.2 mmol). R f = 0.38 (pentane / Et 2 = 1 / 1); purity 98%;[ α ] 20 = 38.0 (c = 2.12, CHCl 3 ); ee 98% (determined via NMR analysis of the corresponding Mosher ester); 1 H-NMR (500.1 MHz, CCl 3 ): δ (ppm) = (m, 5H, 5 C ar H), (m, 2H, CH=CH), 4.50 (s, 2H, PhCH 2 ), (m, 1H, CHH), 3.69 (dt, 2 J = 9.3 Hz, 3 J = 5.5 Hz, 1H, CH 2 Bn), 3.62 (ddd, 2 J = 9.2 Hz, 3 J = 7.3 Hz, 3 J = 5.2 Hz, 1H, CH 2 Bn), 2.79 (br, 1H, H), 2.15 (t, 3 J = 6.7 Hz, 2H, CH 2 CH=CH), (m, 2H, CH 2 CH 2 Bn), 1.66 (dd, 3 J = 6.0 Hz, 4 J = 1.3 Hz, 3H, ); 13 C-NMR (125.8 MHz, CCl 3 ): δ (ppm) = (s, C ar ), (d), (d), (d), (d), (d), 73.2 (t, PhCH 2 ), 70.5 (d, CHH), 68.9 (t, BnCH 2 ), 40.7 (t, CH 2 CH 2 Bn), 35.8 (t, CH 2 CH=CH), 18.0 (q, ); GC-MS(EI): t R = 5.93 min; m / z (rel. Int. [%]): 165 (7), 147 (2), 119 (1), 107 (13), 91 (100), 79 (5), 65 (7), 55 (7). The (R)-enantiomer 17b was obtained starting from (1S,2R)-1-((S)-but-3-en-2-yl)-2- isopropylcyclohexanol. [ α ] 20 analysis of the corresponding Mosher ester). = 4.1 (c = 2.12, CHCl 3 ); ee 98% (determined via NMR (R,E)-Non-2-en-5-ol (18a): In a similar manner 1.85 g (R,E)-non-2-en-5-ol (18a) (13.0 mmol, 65%) was prepared from 2.35 ml distilled valeraldehyde (35) (22.0 mmol). R f = 0.16 (cyclohexane / Et 2 = 9 / 1); purity 98%; [ α ] 20 = 0.8 (c = 1.10, CHCl 3 ); ee 98% (determined via NMR analysis of the corresponding Mosher ester); 1 H-NMR (500.1 MHz, CCl 3 ): δ (ppm) = (m, 1H, CH=CH), (m, 1H, CH=CH), (m, 1H, CHH), (m, 1H, CH 2 CH=CH), 2.04 (dt, 2 J = 14.2 Hz, 3 J = 7.7 Hz, 1H, CH 2 CH=CH), 1.69 (dd, 3 J = 6.4 Hz, 4 J = 0.9 Hz, 3H, CH=CH), 1.63 (br, 1H, H), (m, 6H), 0.90 (t, 3 J = 7.1 Hz, 3H, CH 2 ); 13 C-NMR (125.8 MHz, CCl 3 ): δ (ppm) = (d, CH=CH), (d, CH=CH), 70.9 (d, CHH), 40.7 (t, CH 2 CH=CH), 36.4 (t), 27.9 (t), 22.7 (t), 18.0 (q, CH=CH), 14.0 (q, CH 2 ); GC-MS(EI): t R = 3.59 min; m / z (rel. Int. [%]): 142 (8), 124 (1), 114 (3), 100 (4), 87 (37), 83 (3), 69 (100), 57 (39), 56 (91). S4

6 The (S)-enantiomer 18b was obtained starting from (1S,2R)-1-((S)-but-3-en-2-yl)-2- isopropylcyclohexanol. [ α ] 20 analysis of the corresponding Mosher ester). = 1.3 (c = 1.92, CHCl 3 ); ee 98% (determined via NMR (S,E)-2-thylhept-5-en-3-ol (19a): In a similar manner 1.48 g (S,E)-2-methylhept-5-en-3- ol (19a) (11.6 mmol, 58%) was prepared from 4.72 ml distilled isobutyraldehyde (36) (22.0 mmol). R f = 0.16 (cyclohexane / Et 2 = 9 / 1); purity 98%; [ α ] 20 = 2.3 (c = 0.31, CHCl 3 ); ee 98% (determined via NMR analysis of the corresponding Mosher ester); 1 H-NMR (500.1 MHz, CCl 3 ): δ (ppm) = (m, 1H, CH=CH), (m, 1H, CH=CH), 3.32 (ddd, 3 J = 8.9 Hz, 3 J = 5.5 Hz, 3 J = 3.5 Hz, 1H, CHH), (m, 1H, CH 2 CH=CH), 2.03 (dt, 2 J = 14.0 Hz, 3 J = 8.4 Hz, 1H, CH 2 CH=CH), 1.69 (d, 3 J = 6.2 Hz, 3H, CH=CH), 1.66 (qint, 3 J = 6.2 Hz, 1H, CH 2 ), 1.59 (br, 1H, H), 0.93 (d, 3 J = 7.0 Hz, 3H, CH 2 ), 0.91 (d, 3 J = 7.2 Hz, 3H, CH 2 ); 13 C-NMR (125.8 MHz, CCl 3 ): δ (ppm) = (d, CH=CH), (d, CH=CH), 75.6 (d, CHH), 37.5 (t, CH 2 CH=CH), 33.0 (d, CH), 18.7 (q, ), 18.0 (q, ), 17.6 (q, ); GC-MS(EI): t R = 3.00 min; m / z (rel. Int. [%]): 128 (3), 100 (3), 95 (2), 85 (29), 73 (100), 67 (16), 57 (30), 55 (92). The (R)-enantiomer 19b was obtained starting from (1S,2R)-1-((S)-but-3-en-2-yl)-2- isopropylcyclohexanol. [ α ] 20 analysis of the corresponding Mosher ester). = 2.9 (c = 0.83, CHCl 3 ); ee 98% (determined via NMR (S,E)-1-Cyclohexylpent-3-en-1-ol (20a): In a similar manner 1.74 g (S,E)-1-cyclohexylpent- 3-en-1-ol (20a) (10.3 mmol, 57%) was prepared from 2.43 ml freshly distilled cyclohexylcarbaldehyde (37) (18.2 mmol). R f = 0.16 (cyclohexane / Et 2 = 9 / 1); purity 98%; [ α ] 20 = 7.6 (c = 1.25, CHCl 3 ); ee 98% (determined via NMR analysis of the corresponding Mosher ester); 1 H-NMR (500.1 MHz, CCl 3 ): δ (ppm) = (m, 1H, CH=CH), (m, 1H, CH=CH), 3.32 (ddd, 3 J = 8.9 Hz, 3 J = 5.7 Hz, 3 J = 3.4 Hz, 1H CHH), (m, 1H, CH 2 CH=CH), 2.01 (dt, 2 J = 14.2 Hz, 3 J = 8.2 Hz, 1H, CH 2 CH=CH), (m, 1H), (m, 5H), 1.66 (dd, 3 J = 6.3 Hz, 4 J = 1.0 Hz, 3H, ), (m, 6H); 13 C-NMR (125.8 MHz, CCl 3 ): δ (ppm) = (d, CH=CH), (d, CH=CH), 75.0 (d, CHH), 43.0 (d, CHCHH)), 37.5 (t), 29.0 (t), 28.2 (t), 26.5 (t), 26.3 (t), 26.1 (t), 18.1 (q, ); GC-MS(EI): t R = 4.62 min; m / z (rel. Int. [%]): 168 (2), 113 (23), 111 (11), 95 (100), 83 (11), 67 (14), 57 (5), 55 (19). S5

7 The (R)-enantiomer 20b was obtained starting from (1S,2R)-1-((S)-but-3-en-2-yl)-2- isopropylcyclohexanol. [ α ] 20 analysis of the corresponding Mosher ester). = 7.3 (c = 1.56, CHCl 3 ); ee 98% (determined via NMR (S,E)-1-(Benzyloxy)oct-6-en-4-ol (21): In a similar manner 3.57 g (S,E)-1-(benzyloxy)oct-6- en-4-ol (21) (15.2 mmol, 73%) was prepared from 3.71 g freshly prepared 3- (benzyloxy)butanal [5] (38) (20.8 mmol). R f = 0.38 (pentane / Et 2 = 1 / 1); purity 98%;[ α ] 20 = 5.6 (c = 1.43, CHCl 3 ); ee 98% (determined via NMR analysis of the corresponding Mosher ester); 1 H-NMR (500.1 MHz, CCl 3 ): δ (ppm) = (m, 5H, 5 C ar H), (m, 2H, CH=CH), 4.51 (s, 2H, PhCH 2 ), (m, 1H, CHH, 1H), 3.51 (t, 3 J = 6.2 Hz, 2H), 2.34 (brs, 1H), (m, 1H), (m, 1H), (m, 2H), 1.69 (m, dd, 3 J = 6.0 Hz, 4 J = 1.3 Hz, 3H, CH 3 ), (m, 1H), (m, 1H); 13 C-NMR (125.8 MHz, CCl 3 ): δ (ppm) = 138.2, 128.2, 127.5, 127.4, 127.2, 72.8, 70.7, 70.3, 40.6, 33.6, 26.0, 17.9; GC-MS(EI): t R = 7.47 min; m / z (rel. Int. [%]): 173 (13), 161 (6), 107 (20), 91 (100), 71 (100), 65 (28), 55 (24). (S,E)-Hept-5-en-3-ol (22): In a similar manner 2.23 g (S,E)-Hept-2-en-5-ol (22) (19.5 mmol, 53%) was prepared from 2.14 g freshly distilled propionaldehyde (39) (36.8 mmol). R f = 0.29 (cyclohexane / Et 2 = 9 / 1); purity 98%; [ α ] 20 = 3.5 (c = 0.54, CHCl 3 ); ee 98% (determined via NMR analysis of the corresponding Mosher ester); 1 H-NMR (500.1 MHz, CCl 3 ): δ (ppm) = (m, 1H, CH=CH), (m, 1H, CH=CH), (m, 1H, CHH), (m, 1H, CH 2 CH=CH), (m, 1H, CH 2 CH=CH), 1.69 (dd, 3 J = 6.3 Hz, 4 J = 0.9 Hz, 3H, CH=CH), 1.69 (br, 1H, H), (m, 2H), 0.90 (t, 3 J = 7.1 Hz, 3H,); 13 C-NMR (125.8 MHz, CCl 3 ): δ (ppm) = (CH=CH), (CH=CH), 72.2 (CHH), 40.0 (t, CH 2 CH=CH), 29.2, 17.8, 9.7. (R,E)-1-Phenyl-pent-3-en-1-ol (23): In a similar manner 2.45 g (R,E)-1-Phenyl-pent-3-en-1- ol (23) (15.1 mmol, 65%) was prepared from 2.47 g distilled benzaldehyd (40) (23.2 mmol). R f = 0.21 (cyclohexane / Et 2 = 9 / 1); purity 95%; [ α ] 20 = 55.9 (c = 2.58, CHCl 3 ); ee 98% (determined via NMR analysis of the corresponding Mosher ester); 1 H-NMR (500.1 MHz, CCl 3 ): δ (ppm) = (m, 5H, 5 C ar H), (m, 1H, CH=CH, 1H), (m, 1H, CH=CH), 4.67 (dd, 3 J = 7.9 Hz, 3 J = 5.0 Hz, 1H), (m, 2H), 2.21 (brs, 1H, H), 1.70 (ddd, 3 J = 6.4 Hz, 3 J = 2.5 Hz, 3 J = 1.3 Hz, 3H). S6

8 tert-butyl(hex-5-ynyloxy)dimethylsilane (27) [6, 7] : THF (42) (8.2 ml, 100 mmol, 2.50 eq), 12.0 g sodium iodide (80.0 mmol, 2.00 eq) and 6.03 g tert-butylchlorodimethylsilane (40.0 mmol, 1.00 eq) were dissolved in 80 ml dry acetonitrile and the solution was heated under an argon atmosphere for 16 h at 55 C to yield a yellow suspension. After addition of 150 ml water the biphasic mixture was separated and the aqueous phase was extracted with pentane / Et 2 = 9 / 1 (3 100 ml). The combined organic layers were rinsed with aqueous sodium hydrogensulfite solution (100 ml) and brine (100 ml), dried (Na 2 S 4 ) and concentrated to give 12.6 g (4-iodobutoxy)(tert-butyl)dimethylsilane (39.9 mmol, 100%) as pure, colorless liquid. It was used without further purification in the next step. R f = 0.58 (cyclohexane / Et 2 = 9 / 1); purity = 95%; 1 H-NMR (500.1 MHz, CCl 3 ): δ (ppm) = 3.58 (t, 3 J = 6.2 Hz, 2H, CH 2 TBS), 3.16 (t, 3 J = 7.0 Hz, 2H, CH 2 I), 1.85 (quint, 3 J = 7.1 Hz, 2H, CH 2 CH 2 I), 1.61 (tt, 3 J = 7.3 Hz, 3 J = 6.4 Hz, 2H, CH 2 CH 2 TBS), 0.83 (s, 9H, C 3 ), 0.01 (s, 6H Si 2 ); 13 C-NMR (125.8 MHz, CCl 3 ): δ (ppm) = 61.9 (t, CH 2 TBS), 33.5 (t, CH 2 CH 2 TBS), 30.2 (t, CH 2 CH 2 I), 25.9 (q, C 3 ), 18.3 (s, C 3 ), 7.0 (t, CH 2 I), -5.4 (q, Si 2 ); GC-MS(EI): t R = 2.66 min; m / z (rel. Int. [%]): 299 (1), 257 (85), 215 (100), 185 (76), 129 (22), 115 (9), 101 (16), 75 (31), 55 (30). (4-Iodobutoxy)(tert-butyl)dimethylsilane (5.00 g, 15.9 mmol, 1.00 eq) was dissolved in 45 ml dry pentane and mixed with 30 ml dry MS. At room temperature 2.44 g lithium acetylide ETA complex (purity: 90%, 23.9 mmol, 1.50 eq) was added portionwise. Vigorous stirring was continued for 4 h until no starting material could be detected any more via GC-MS. The reaction mixture was carefully quenched at 0 C with saturated, aqueous ammonium chloride solution and water (150 ml). After separation of the biphasic mixture the aqueous phase was extracted with pentane (3 100 ml), the combined organic layers were washed with brine (100 ml), dried (MgS 4 ) and concentrated to give a bright yellow liquid. The crude product was filtered through a plug of silica (cyclohexane / Et 2 = 98 / 2) to yield 2.96 g tert- Butyl(hex-5-ynyloxy)dimethylsilane (27) (13.9 mmol, 88%) as colorless liquid. R f = 0.50 (cyclohexane / Et 2 = 98 / 2); purity 98%; 1 H-NMR (500.1 MHz, CCl 3 ): δ (ppm) = 3.57 (t, 3 J = 6.1 Hz, 2H, CH 2 TBS), 2.15 (td, 3 J = 6.9 Hz, 3 J = 2.7 Hz, 2H, CH 2 C CH), 1.87 (t, 4 J = 2.7 Hz, 1H, C CH), (m, 4H, CH 2 CH 2 CH 2 TBS), 0.83 (s, 9H, C 3 ), 0.01 (s, 6H, Si 2 ); 13 C-NMR (125.8 MHz, CCl 3 ): δ (ppm) = 84.5 (s, C CH), 68.2 (d, C CH), 62.5 (t, CH 2 TBS), 31.8 (t, CH 2 CH 2 TBS), 25.9 (q, C 3 ), 24.9 (t, CH 2 CH 2 C CH)), 22.4 (s, C 3 ), 18.2 (t, CH 2 C CH), 5.4 (q, Si 2 ). S7

9 2-((R)-2-thoxyhex-5-ynyloxy)-tetrahydro-2H-pyran (44a): (S)-Glycidol (10.0 ml, 151 mmol, 1.00 eq) and 18.4 ml dihydropydran (203 mmol, 1.35 eq) were dissolved in 150 ml dry dichloromethane. At 0 C 860 mg p-toluenesulfonic acid (4.52 mmol, 0.03 eq) was added. The reaction mixture was stirred for 30 min at room temperature before it was quenched with 914 mg triethylamine (9.04 mmol, 0.06 eq). Without work up the mixture was concentrated and purified by filtration through a silica plug (cyclohexane / EtAc = 4 / 1 + 1% NEt 3 ) to yield 23.7 g 2-(((R)-oxiran-2-yl)methoxy)-tetrahydro-2H-pyran (43a) (150 mmol, 99%) as colorless liquid. R f = 0.19 (cyclohexane / Et 2 = 9 / 1); purity 98%; [ α ] 20 = 4.4 (c = 2.99, CHCl 3 ); 1 H-NMR (500.1 MHz, CCl 3 ): δ (ppm) = 4.62 (t, 3 J = 3.6 Hz, 0.5H, CH), 4.60 (t, 3 J = 3.5 Hz, 0.5H, CH), 3.90 (dd, 2 J = 11.8 Hz, 3 J = 3.0 Hz, 0.5H), 3.84 (dd, 2 J = 7.7 Hz, 3 J = 3.9 Hz, 0.5H), 3.80 (dd, 2 J = 7.9 Hz, 3 J = 4.1 Hz, 0.5H), 3.68 (dd, 2 J = 11.8 Hz, 3 J = 5.0 Hz, 0.5H), 3.64 (dd, 2 J = 11.7 Hz, 3 J = 3.4 Hz, 0.5H), (m, 1H), 3.35 (dd, 2 J = 11.7 Hz, 3 J = 6.4 Hz, 0.5H), (m, 1H), 3.77 (dd, 3 J = 5.0 Hz, 3 J = 2.3 Hz, 0.5H), 3.76 (dd, 3 J = 5.1 Hz, 3 J = 2.1 Hz, 0.5H), 2.64 (dd, 3 J = 5.0 Hz, 3 J = 2.8 Hz, 0.5H), 2.55 (dd, 3 J = 4.9 Hz, 3 J = 2.6 Hz, 0.5H), (m, 6H); 13 C-NMR (125.8 MHz, CCl 3 ): δ (ppm) = 98.8 (d, CH), 98.7 (d, CH), 68.4 (t, CH 2 THP), 67.2 (t, CH 2 THP), 62.1 (t), 62.0 (t), 50.9 (d, CH), 50.5 (d, CH), 44.5 (t, CH 2 CH), 44.4 (t, CH 2 CH), 30.4 (t), 30.3 (t), 25.3 (t), 25.3 (t), 19.2 (t), 19.1 (t); GC-MS(EI): t R = 4.15 min; m / z (rel. Int. [%]): 157 (2), 140 (1), 129 (3), 101 (35), 85 (100), 72 (6), 67 (19), 57 (59), 55 (27). Allenylmagnesium bromide freshly (!) prepared from 5.60 ml distilled propargylbromide (80% in toluene, 50.0 mmol, 2.00 eq), 1.34 magnesium (55.0 mmol, 2.20 eq) and 68 mg mercury(ii) chloride (0.25 mmol, 0.01 eq) in 50 ml dry diethylether was stirred at 10 C. [8] Via a dropping funnel 3.96 g 2-(((R)-oxiran-2-yl)methoxy)-tetrahydro-2H-pyran (43a) (25.0 mmol, 1.00 eq) dissolved in 25 ml dry diethylether was added over a time period of 30 min. After 5 min the reaction was monitored by GC-MS and quenched at 10 C with saturated, aqueous ammonium chloride solution and water (100 ml). After separation of the biphasic mixture the aqueous phase was extracted with diethylether (3 100 ml), the combined organic layers were washed with brine (100 ml), dried (MgS 4 ) and concentrated. The crude product was purified by column chromatography (cyclohexane / EtAc = 4 / 1). (R)-1-(Tetrahydro-2H-pyran-2-yloxy)hex-5-yn-2-ol (4.56 g, 23.0 mmol, 92%) was obtained as yellow oil. R f = 0.22 (cyclohexane / EtAc = 4 / 1); purity = 97%; [ α ] 20 = 7.7 (c = 1.95, CHCl 3 ); ee 98% (determined via NMR analysis of the corresponding Mosher ester); S8

10 1 H-NMR (500.1 MHz, CCl 3 ): δ (ppm) = (m, 1H, CHH), (m, 5H), 3.19 (br, 0.5H, H), 2.82 (br, 0.5H, H), 2.33 (t, 3 J = 7.2 Hz, 1H, CH 2 C CH), 2.32 (t, 3 J = 7.2 Hz, 1H, CH 2 C CH), 1.92 (t, 4 J = 2.5 Hz, 1H, C CH), (m, 8H); 13 C-NMR (125.8 MHz, CCl 3 ): δ (ppm) = (d, CH), (d, CH), 84.2 (s, C CH), 84.1 (s, C CH), 73.7 (t, CH 2 THP), 73.0 (t, CH 2 THP), 69.4 (d, CHH), 69.3 (d, CHH), 68.7 (d, C CH), 63.3 (t), 32.1 (t), 31.9 (t), 30.9 (t), 25.3 (t), 20.1 (t), 20.0 (t), 15.0 (t, CH 2 C CH), 14.9 (t, CH 2 C CH); GC-MS(EI): t R = 5.11 min; m / z (rel. Int. [%]): 167 (2), 137 (1), 115 (3), 101 (4), 85 (100), 79 (4), 67 (13), 57 (18), 55 (16). To an ice-cold suspension of 1.51 g sodium hydride (37.8 mmol, 1.50 eq) washed with pentane and 3.14 ml methyl iodide (50.4 mmol, 2.00 eq) in 50 ml dry THF a solution of 5.00 g (R)-1-(tetrahydro-2H-pyran-2-yloxy)hex-5-yn-2-ol in 10 ml dry THF was added dropwise. After stirring for 1 h at room temperature TLC analysis showed complete conversion. The reaction was quenched at 0 C with saturated, aqueous ammonium chloride solution and water (50 ml). After separation of the biphasic mixture the aqueous phase was extracted with diethylether (3 50 ml), the combined organic layers were washed with brine (50 ml), dried (MgS 4 ) and concentrated. The crude product was purified by column chromatography (cyclohexane / EtAc = 9 / 1 + 1% NEt 3 ) to yield 3.82 g 2-((R)-2- methoxyhex-5-ynyloxy)-tetrahydro-2h-pyran (44a) (18.0 mmmol, 71%) as colorless oil. R f = 0.36 (cyclohexane / EtAc = 4 / 1); purity 98%; [ α ] 20 = 27.7 (c = 2.88, CHCl 3 ); 1 H-NMR (500.1 MHz, CCl 3 ): δ (ppm) = 4.60 (t, 3 J = 3.4 Hz, 0.5H, CH), 4.59 (t, 3 J = 3.6 Hz, 0.5H, CH), (m, 2H), 3.75 (t, 3 J = 4.0 Hz, 0.5H), 3.73 (t, 3 J = 3.7 Hz, 0.5H), (m, 3H), 3.43 (s, 1.5H, ), 3.42 (s, 1.5H, ), (m, 2H, CH 2 C CH), 1.93 (t, 4 J = 2.6 Hz, 1H, C CH), (m, 7H); 13 C-NMR (125.8 MHz, CCl 3 ): δ (ppm) = 99.0 (d, CH), 98.7 (d, CH), 84.1 (s, C CH), 78.5 (d, CH), 78.4 (d, CH), 69.1 (d, C CH), 68.4 (t, CH 2 THP), 68.3 (t, CH 2 THP), 62.3 (t), 61.9 (t), 58.0 (q, ), 57.8 (q, ), 30.6 (t), 30.6 (t), 30.5 (t), 30.4 (t), 25.4 (t), 19.3 (t), 19.2 (t), 14.6 (t, CH 2 C CH), 14.5 (t, CH 2 C CH); GC-MS(EI): t R = 5.00 min; m / z (rel. Int. [%]): 150 (2), 124 (4), 115 (4), 97 (22), 85 (100), 79 (12), 67 (21), 57 (16). The (S)-enantiomer 44b was obtained starting from (R)-glycidol. [ α ] 20 = 26.2 (c = 1.52, CHCl 3 ). 2-((R)-2-Benzyloxyhex-5-ynyloxy)-tetrahydro-2H-pyran (45a): To an ice-cold suspension of 4.74 g pentane-washed sodium hydride (119 mmmol, 1.50 eq) and 18.8 ml benzylbromide S9

11 (158 mmol, 2.00 eq) in 100 ml dry THF a solution of 15.7 g (R)-1-(tetrahydro-2H-pyran-2- yloxy)hex-5-yn-2-ol (79.0 mmol, 1.00 eq) in 50 ml dry THF was added dropwise. After 16 h stirring at room temperature TLC analysis showed complete conversion and the reaction was quenched at 0 C with saturated, aqueous ammonium chloride solution and water (50 ml). After separation of the biphasic mixture the aqueous phase was extracted with diethylether (3 50 ml), the combined organic layers were washed with brine (50 ml), dried (MgS 4 ) and concentrated. The crude product was purified by column chromatography (cyclohexane / EtAc = 95 / 5 8 / 2 + 1% NEt 3 ) to yield 11.8 g 2-((R)-2-benzyloxyhex-5- ynyloxy)-tetrahydro-2h-pyran (45a) (40.8 mmmol, 52%) as colorless oil. R f = 0.20 (cyclohexane / Et 2 = 9 / 1); purity 98%; [ α ] 20 = 47.0 (c = 3.33, CHCl 3 ); 1 H-NMR (500.1 MHz, CCl 3 ): δ (ppm) = (m, 5H, 5 C ar H), 4.75 (d, 2 J = 11.5 Hz, 1H, PhCH 2 ), 4.64 (t, 3 J = 3.5 Hz, 1H, CH), 4.60 (dd, 2 J = 11.5 Hz, 3 J = 4.5Hz, 1H, PhCH 2 ), (m, 3H), (m, 2H), 2.34 (t, 3 J = 6.6 Hz, 2H, CH 2 C CH), 1.95 (t, 4 J = 2.6 Hz, 0.5H, C CH), 1.95 (t, 4 J = 2.5 Hz, 0.5H, C CH), (m, 8H); 13 C-NMR (125.8 MHz, CCl 3 ): δ (ppm) = (s, C ar ), (d, C ar ), (d, C ar ), (d, C ar ), 99.0 (d, CH), 98.7 (d, CH), 76.6 (d, CHBn), 76.5 (d, CHBn), 72.5 (t, PhCH 2 ), 72.2 (t, PhCH 2 ), 69.9 (d, C CH), 69.1 (d, C CH), 68.5 (t; CH 2 THP), 62.0 (t), 61.8 (t), 31.0 (t), 30.5 (t), 30.4 (t), 25.4 (t), 19.3 (t), 19.2 (t), 14.7 (t, CH 2 C CH), 14.6 (t, CH 2 C CH); GC- MS(EI): t R = 6.79 min; m / z (rel. Int. [%]): 203 (70), 155 (5), 129 (15), 107 (35), 91 (100), 85 (97), 79 (14), 65 (22), 57 (18). The (S)-enantiomer 45b was obtained starting from (R)-glycidol. [ α ] 20 = 47.2 (c = 2.48, CHCl 3 ). 2-((S)-1-thyloxyhept-6-yn-2-yloxy)-tetrahydro-2H-pyran (49): (4-Bromobut-1- ynyl)trimethylsilane was synthesized in four steps starting from 3-butyn-1-ol in an overall yield of 78%. Purification was achieved by distillation (bp = 35 C, 3.0 mbar, 10 cm Vigreux column). R f = 0.63 (cyclohexane / EtAc = 4 / 1); purity 98%; 1 H-NMR (500.1 MHz, CCl 3 ): δ (ppm) = 3.42 (t, 3 J = 7.5 Hz, 2H, CH 2 Br), 2.76 (t, 3 J = 7.5 Hz, 2H, CH 2 CH 2 Br), 0.15 (s, 9H, Si 3 ); 13 C-NMR (125.8 MHz, CCl 3 ): δ (ppm) = (s, C CSi 3 ), 87.1 (s, C CSi 3 ), 29.3 (t, CH 2 Br), 24.4 (t; CH 2 CH 2 Br), 0.07 (q, Si 3 ); GC-MS(EI): t R = 3.48 min; m / z (rel. Int. [%]): 206 (1), 204 (1), 191 (100), 189 (99), 163 (79), 161 (76), 139 (45), 137 (45), 109 (33). S10

12 A three-necked flask equipped with condenser and dropping funnel was charged with 2.69 g magnesium turnings (111 mmol, 1.95 eq) and 15 ml dry THF. After activation of magnesium with iodide a solution of 15.1 g (4-bromobut-1-ynyl)trimethylsilane (73.7 mmol, 1.30 eq) in 85 ml dry THF was added dropwise leading to reflux. After complete addition the suspension was stirred at 60 C for 30 min. The Grignard reagent 48 was allowed to settle, transferred via a cannula to another flask and cooled to -40 C. Copper(I) iodide (540 mg, 2.84 mmol, 0.05 eq) was added and stirring was continued for 15 min. A solution of commercially available 5.00 g (S)-2-(methyloxymethyl)oxirane (46) (56.7 mmol, 1.00 eq) in 50 ml dry THF was added dropwise to the brown suspension at 40 C over a period of 30 min. After further 30 min TLC analysis indicated that no starting material was left and the reaction was quenched at 10 C with saturated, aqueous ammonium chloride solution and water (150 ml). After separation of the biphasic mixture the aqueous phase was extracted with diethylether (3 100 ml), the combined organic layers were washed with brine (100 ml), dried (MgS 4 ) and concentrated. Purification was achieved by column chromatography (cyclohexane / EtAc = 6 / 1) to give 12.0 g (S)-1-methoxy-7-(trimethylsilyl)hept-6-yn-2-ol (56.1 mmol, 99%) as yellow oil. R f = 0.18 (cyclohexane / EtAc = 4 / 1); GC-MS(EI): t R = 4.73 min; m / z (rel. Int. [%]): 199 (1), 169 (10), 153 (13), 141 (2), 129 (42), 109 (14), 101 (14), 89 (31), 73 (100). (S)-1-thoxy-7-(trimethylsilyl)hept-6-yn-2-ol (12.0 g, 56.1 mmol) was dissolved in 200 ml methanol and 4.0 g potassium carbonate were added at room temperature. Stirring was continued for 5 h. The reaction mixture was quenched with saturated, aqueous ammonium chloride solution and water (350 ml) followed by extraction with diethylether (3 200 ml). The combined organic layers were washed with brine (150 ml), dried (MgS 4 ) and concentrated. The crude product was purified by Kugelrohr distillation (70 C, 0.1 mbar) to yield 5.74 g (S)-1-methoxyhept-6-yn-2-ol (40.4 mmol, 71%) as colorless liquid. Purity 98%; ee 98% (determined via NMR analysis of the corresponding Mosher ester); 1 H-NMR (500.1 MHz, CCl 3 ): δ (ppm) = (m, 1H, CHH), (m, 4H,, CH 2 ), 3.23 (t, 3 J = 8.6 Hz, 1H, CH 2 ), 3.23 (br, 1H, H), (m, 2H, CH 2 C CH), (m, 1H, C CH), (m, 4H); 13 C-NMR (125.8 MHz, CCl 3 ): δ (ppm) = 84.3 (s, C CH), 69.9 (d, C CH), 68.8 (d, CH 2 H), 68.7 (t, CH 2 ), 59.1 (q, ), 32.2 (t, CH 2 CH 2 CH 2 C CH), 24.6 (t, CH 2 CH 2 C CH), 18.5 (t, CH 2 C CH); GC-MS(EI): t R = 3.59 min; m / z (rel. Int. [%]): 123 (2), 109 (4), 97 (93), 91 (8), 79 (64), 69 (100), 67 (44), 57 (65), 55 (51). S11

13 (S)-1-thoxyhept-6-yn-2-ol (5.74 g, 40.4 mmol, 1.00 eq) and 4.90 ml 3,4-dihydro-2H-pyran (54.5 mmol, 1.35 eq) were dissolved in 50 ml dry dichloromethane and treated at 0 C with 231 mg p-toluenesulfonic acid (1.21 mmol, 0.03 eq). After 2 h stirring at room temperature the reaction mixture was quenched with 245 mg triethylamine (2.42 mmol, 0.06 eq) and concentrated without aqueous work up. The crude product was filtered through a silica plug (cyclohexane / EtAc = 9 / 1 + 1% NEt 3 ) to give 8.58 g 2-((S)-1-methyloxyhept-6-yn-2- yloxy)-tetrahydro-2h-pyran (49) (37.9 mmol, 94%) as slightly yellow liquid. R f = 0.20 (cyclohexane / Et 2 = 9 / 1); purity 98%; [ α ] 20 = 12.0 (c = 2.39, CHCl 3 ); 1 H-NMR (500.1 MHz, CCl 3 ): δ (ppm) = 4.74 (dd, 3 J = 4.6 Hz, 3 J = 2.9 Hz, 0.5H, CH), 4.60 (dd, 3 J = 4.8 Hz, 3 J = 2.8 Hz, 0.5 Hz, CH), (m, 1.5H), (m, 0.5H), (m, 3H), 3.32 (s, 1.5H, ), 3.29 (s, 1.5H, ), (m, 2H, CH 2 C CH), 1.90 (t, 4 J = 2.6 Hz, 0.5H, C CH), 1.89 (t, 4 J = 2.6 Hz, 0.5H, C CH), (m, 10H); 13 C-NMR (125.8 MHz, CCl 3 ): δ (ppm) = 99.0 (d, CH), 97.8 (d, CH), 84.5 (s, C CH), 84.4 (s, C CH), 76.0 (d), 75.2 (t), 74.1 (d), 68.5 (d, C CH), 68.4 (d, C CH), 62.9 (t), 62.8 (t), 59.3 (q, ), 59.2 (q, ), 31.7 (t), 31.1 (t), 31.0 (t), 30.8 (t), 25.6 (t), 25.5 (t), 24.7 (t), 24.5 (t), 20.0 (t), 19.9 (t), 19.8 (t), 18.7 (t), 18.5 (t); GC-MS(EI): t R = 5.23 min; m / z (rel. Int. [%]): 181 (4), 101 (2), 96 (1), 93 (13), 85 (100), 77 (11), 67 (19), 57 (13), 55 (10). 2-((S)-1-Benzyloxyhept-6-yn-2-yloxy)-tetrahydro-2H-pyran (50): Sodium hydride (3.72 g, 93.0 mmol, 1.30 eq) was washed with pentane and suspended in 70 ml dry MF. After addition of 12.7 ml benzylbromide (107 mmol, 1.50 eq) 5.0 ml (S)-glycidol (71.6 mmol, 1.00 eq) was added dropwise at 0 C. Stirring at room temperature continued for 3 h and the reaction mixture was quenched at 0 C with saturated, aqueous ammonium chloride solution and water (150 ml) followed by extraction with diethylether (3 100 ml). The combined organic layers were washed with brine (100 ml), dried (MgS 4 ) and concentrated. The crude product was purified by column chromatography (cyclohexane / EtAc = 7 / 1 6 / 1) to yield 11.8 g (S)-2-((benzyloxy)methyl)oxirane (47) (71.7 mmol, 100%) as colorless liquid. R f = 0.63 (cyclohexane / EtAc = 6 / 1); purity 98%; [ α ] 20 = 1.6 (c = 2.03, CHCl 3 ) (lit. [9] : 1.65 ); 1 H-NMR (500.1 MHz, CCl 3 ): δ (ppm) = (m, 5H, 5 C ar H), 4.62 (d, 2 J = 11.7 Hz, 1H, PhCH 2 ), 4.57 (d, 2 J = 11.7 Hz, PhCH 2 ), 3.77 (dd, 2 J = 11.5 Hz, 1H, CH 2 Bn), 3.44 (dd, 2 J = 11.5 Hz, 1H, CH 2 Bn), 3.19 (ddt, 3 J = 6.0 Hz, 3 J = 4.0 Hz, 3 J = 3.0 Hz, 1H, CH), 2.80 (dd, 2 J = 5.0 Hz, 3 J = 4.2 Hz, 1H, CH 2 CH), 2.62 (dd, 2 J = 5.2 Hz, 3 J = 2.7 Hz, 1H, CH 2 CH); 13 C-NMR (125.8 MHz, CCl 3 ): δ (ppm) = (s, C ar ), (d, C ar ), (d, C ar ), (d, C ar ), 73.3 (PhCH 2 ), 70.9 (t, BnCH 2 ), 50.9 (d, CH), 44.2 (t, S12

14 CH 2 CH); GC-MS(EI): =4.71 min; m / z (rel. Int. [%]): 164 (3), 133 (1), 107 (51), 105 (36), 91 (100), 79 (30), 77 (19), 65 (21), 51 (9). Starting from 14.2 g (S)-2-((benzyloxy)methyl)oxirane (47) (86.2 mmol, 1.00 eq) 26.0 g (S)- 1-benzyloxy-7-(trimethylsilyl)hept-6-yn-2-ol (89.5 mmol, 100%) was obtained in a similar manner as described above. R f = 0.66 (cyclohexane / EtAc = 6 / 1); purity 98%; [ α ] 20 = 8.8 (c = 2.47, CHCl 3 ); ee 98% (determined via NMR analysis of the corresponding Mosher ester); 1 H-NMR (500.1 MHz, CCl 3 ): δ (ppm) = (m, 5H, 5 C ar H), 4.53 (s, 2H, PhCH 2 ), (m, 1H, CHH), 3.49 (dd, 2 J = 9.4 Hz, 3 J = 3.1 Hz, 1H, BnCH 2 ), 3.32 (dd, 2 J = 9.5 Hz, 3 J = 7.8 Hz, 1H, BnCH 2 ), 2.40 (br, 1H, H), 2.23 (t, 3 J = 7.0 Hz, 2H, CH 2 C CH), (m, 4H), 0.12 (s, 9H, Si 3 ); 13 C-NMR (125.8 MHz, CCl 3 ): δ (ppm) = (s, C ar ), (d, C ar ), (d, C ar ), (d, C ar ), (s, C CH), 84.9 (d, C CH), 74.7 (t, PhCH 2 ), 73.5 (t, BnCH 2 ), 70.0 (d, CHH), 32.2 (d), 24.7 (d), 19.9 (d, CH 2 C CH), 0.3 (q, Si 3 ); GC-MS(EI): t R = 7.55 min; m / z (rel. Int. [%]): 206 (8), 205 (4), 155 (1), 141 (4), 97 (5), 91 (66), 85 (100), 73 (16), 57 (9). (S)-1-Benzyloxy-7-(trimethylsilyl)hept-6-yn-2-ol (26.0 g, 89.5 mmol, 1.00 eq) and 11.0 ml 3,4-dihydro-2H-pyran (120 mmol, 1.35 eq) were dissolved in 90 ml dry dichloromethane and treated at 0 C with 509 mg p-toluenesulfonic acid (2.67 mmol, 0.03 eq). After 2 h stirring the reaction mixture was quenched with 1.02 g triethylamine (5.34 mmol, 0.06 eq) and concentrated without aqueous work up. The crude product was filtered through a silica plug (cyclohexane / EtAc = 9 / 1 + 1% NEt 3 ) to give 33.4 g ((S)-7-benzyloxy-6-(tetrahydro-2Hpyran-2-yloxy)hept-1-ynyl)trimethylsilane (89.5 mmol, 100%) as yellow liquid. R f = 0.46 (cyclohexane / Et 2 = 9 / 1); [ α ] 20 = 7.0 (c = 4.47, CHCl 3 ); GC-MS(EI): t R = 7.55 min; m / z (rel. Int. [%]): 289 (1), 206 (11), 141 (5), 109 (4), 97 (6), 91 (71), 85 (100), 73 (19), 57 (10). ((S)-7-Benzyloxy-6-(tetrahydro-2H-pyran-2-yloxy)hept-1-ynyl)trimethylsilane (33.4 g, 89.5 mmol) was dissolved in 400 ml methanol and 8.0 g potassium carbonate was added at room temperature. Stirring was continued for 3 h. The reaction mixture was quenched with saturated, aqueous ammonium chloride solution and water (650 ml) followed by extraction with diethylether (3 300 ml). The combined organic layers were washed with brine (300 ml), dried (MgS 4 ) and concentrated. The crude product was purified by column chromatography (cyclohexane / EtAc = 9 / 1 + 1% NEt 3 ) to yield 25.9 g 2-((S)-1- benzyloxyhept-6-yn-2-yloxy)-tetrahydro-2h-pyran (50) (85.6 mmol, 96%) as yellow liquid. S13

15 R f = 0.19 (cyclohexane / Et 2 = 9 / 1); purity 98%; [ α ] 20 = 11.5 (c = 3.90, CHCl 3 ); 1 H-NMR (500.1 MHz, CCl 3 ): δ (ppm) = (m, 5H, 5 CH ar ), (m, 1H, CH), 4.55 (d, 2 J = 14.7 Hz, 1H, PhCH 2 ), 4.54 (d, 2 J = 14.0 Hz, 1H, PhCH 2 ), (m, 2H), 3.79 (quint, 3 J = 5.5 Hz, 0.5H), 3.63 (dd, 3 J = 9.6 Hz, 3 J = 5.1 Hz, 0.5H), (m, 2H), (m, 2H, CH 2 C CH)), 1.95 (t, 4 J = 2.7 Hz, 0.5H, C CH), 1.94 (t, 4 J = 2.7 Hz, 0.5H, C CH), (m, 10H); 13 C-NMR (125.8 MHz, CCl 3 ): δ (ppm) = (s, C ar ), (s, C ar ), (d, C ar ), (d, C ar ), (d, C ar ), (d, C ar ), (d, C ar ), (d, C ar ), 98.8 (d, CH), 98.0 (d, CH), 84.5 (s, C CH), 84.4 (s, C CH), 76.1 (d,chthp), 74.4 (d, CHTHP), 73.3 (t, PhCH 2 ), 72.7 (t, BnCH 2 ), 68.6 (d, C CH), 68.5 (d, C CH), 62.9 (t), 62.6 (t), 31.7 (t), 31.2 (t), 30.9 (t), 25.6 (t), 25.5 (t), 25.0 (t), 24.4 (t), 20.0 (t), 19.8 (t), 18.7 (t), 18.5 (t); GC-MS(EI): t R = 6.98 min; m / z (rel. Int. [%]): 217 (17), 205 (4), 171 (1), 141 (2), 129 (2), 107 (7), 91 (85), 85 (100), 67 (16). 2-((S)-2,2-imethyl-1,3-dioxolan-4-yl)ethanol (51): (S)-Malic acid (10.0 g, 74.5 mmol, 1.00 eq) was dissolved in 50 ml dry THF at room temperature and cooled to 0 C. To the icecold solution a mixture of 37.0 ml trimethyl borate (330 mmol, 4.43 eq) and 23.0 ml borane dimethylsulfide complex (242 mmol, 3.25 eq) in 100 ml dry THF was added via a dropping funnel over 45 min and stirred for two days at room temperature. The reaction was cooled to 0 C and 60 ml dry methanol was added dropwise to quench the borohydride. The mixture was concentrated to dryness and filtered through a silica plug (CH 2 Cl 2 / H = 9 / 1) to yield 7.77 g (S)-butane-1,2,4-triol (72.2 mmol, 98%) as colorless oil. R f = 0.35 (CH 2 Cl 2 / H = 9 / 1); purity = 95%; [ α ] 20 = 0.7 (c = 1.07, CHCl 3 ); S14 1 H-NMR (500.1 MHz, ): δ (ppm) = 3.75 (ddt, 3 J = 8.7 Hz, 3 J = 6.2 Hz, 3 J = 4.4 Hz, 1H, CHCH 2 ), 3.70 (t, 3 J = 5.9 Hz, 2H, CH 2 H), 3.50 (dd, 2 J = 11.2 Hz, 3 J = 4.7 Hz, 1H, CHCH 2 ), 3.46 ( 2 J = 11.1 Hz, 3 J = 6.4 Hz, 1H, CHCH 2 ), 1.73 (ddt, 2 J = 14.0 Hz, 3 J = 4.0 Hz, 3 J = 7.1 Hz, 1H, CH 2 CH 2 H), 1.60 (ddt, 2 J = 14.2 Hz, 3 J = 8.4 Hz, 3 J = 5.8 Hz, 1H, CH 2 CH 2 H); 13 C-NMR (125.8 MHz, CCl 3 ): δ (ppm) = 70.7 (d, CHH), 67.5 (t, CHCH 2 ), 60.0 (t, CH 2 H), 37.1 (t, CH 2 CH 2 H). (S)-Butane-1,2,4-triol (7.77 g, 72.2 mmol, 1.00 eq) was dissolved in 150 ml dry acetone and 17.3 water-free copper(ii) sulfate (108.3 mmol, 1.50 eq) was added. At room temperature 687 mg p-toluenesulfonic acid (3.61 mmol, 0.05 eq) was added and the mixture was stirred for three days at room temperature. The suspension turned from colorless to blue. An excess of solid sodium bicarbonate was added and the suspension was stirred for 60 min. It was

16 filtered, concentrated, dissolved in dichloromethane, concentrated on silica and purified by column chromatography (cyclohexane / EtAc = 2 / 1). 2-((S)-2,2-imethyl-1,3-dioxolan-4- yl)ethanol (51) (10.1 g, 57.8 mmol, 80%) was received as colorless oil. R f = 0.28 (cyclohexane / EtAc = 2 / 1); purity 98%; [ α ] 20 = 2.1 (c = 1.61, CHCl 3 ) (lit. [10] : 1.7 ); 1 H-NMR (500.1 MHz, CCl 3 ): δ (ppm) = 4.23 (quint, 3 J = 4.23 Hz, 1H, CH 2 CH), 4.05 (t, 3 J = 7.0 Hz, 1H, CH 2 H), (m, 2H, CH 2 CH), 3.55 (t, 3 J = 7.9 Hz, 1H, CH 2 H), 2.64 (br, 1H, H), (m, 2H, CH 2 CH 2 H), 1.38 (s, 3H, CH 3 ), 1.32 (s, 3H, CH 3 ); 13 C-NMR (125.8 MHz, CCl 3 ): δ (ppm) = (s, C), 74.9 (d, CH 2 CH), 69.5 (t, CH 2 CH), 60.4 (t, CH 2 H), 35.8 (t, CH 2 CH 2 H), 26.9 (q, ), 25.7 (q, ); GC-MS(EI): t R = 3.45 min; m / z (rel. Int. [%]): 131 (100), 101 (12), 85 (10), 71 (77), 59 (23). (E)-4-((S)-2,2-dimethyl-1,3-dioxolan-4-yl)but-2-en-1-ol (52): 2-((S)-2,2-imethyl-1,3- dioxolan-4-yl)ethanol (51) (18.3 g, 120 mmol, 1.00 eq) and 188 mg TEMP (1.20 mmol, 0.01 eq) was dissolved in 48 ml dichloromethane and cooled to -15 C. [11] A solution of 1.43 g potassium bromide (12.0 mmol, 0.10 eq) and 1.60 g sodium bicarbonate in 96 ml aqueous 1.38 M sodium hypochlorite solution (132 mmol, 1.10 eq) was added dropwise. The temperature did not rise above 0 C. Five minutes after complete addition a saturated solution of sodium thiosulfate (100 ml) was added in excess. The organic phase was separated and the aqueous phase was extracted with dichloromethane (3 50 ml). The combined organic layers were washed with saturated bicarbonate solution (100 ml) and brine (100 ml), dried (MgSe 4 ) and concentrated. The slightly orange oil (13.7 g, 94.8 mmol, 79%) was used without further purification in the next step. R f = 0.20 (cyclohexane / EtAc = 4 / 1); purity 98%; [ α ] 20 = 2.8 (c = 2.14, CHCl 3 ); 1 H-NMR (500.1 MHz, CCl 3 ): δ (ppm) = 9.78 (t, 3 J = 1.63 Hz, 1H, CH()), 4.49 (quint, 3 J = 6.4 Hz, 1H, CH), 4.17 (dd, 2 J = 8.4 Hz, 3 J = 6.2 Hz, 1H, CH 2 CH), 3.57 (dd, 2 J = 8.4 Hz, 3 J = 6.7 Hz, 1H, CH 2 CH), 2.82 (ddd, 2 J = 17.3 Hz, 3 J = 6.6 Hz, 3 J = 1.8 Hz, 1H, CH 2 CH()), 2.63 (ddd, 2 J = 17.3 Hz, 3 J = 6.0 Hz, 3 J = 1.3 Hz, 1H, CH 2 CH()), 1.40 (s, 3H, ), 1.34 (s, 3H, ); 13 C-NMR (125.8 MHz, CCl 3 ): δ (ppm) = (d, CH()), (s, C), 70.6 (d, CH), 69.1 (t, CH 2 ), 47.9 (t, CH 2 CH()), 26.8 (q, ), 25.4 (q, ); GC-MS(EI): t R = 3.17 min; m / z (rel. Int. [%]): 129 (24), 115 (3), 101 (7), 85 (11), 72 (11), 69 (100), 59 (17), 57 (6). 2-((S)-2,2-imethyl-1,3-dioxolan-4-yl)acetaldehyde (12.0 g, 83.2 g, 1.00 eq) was dissolved in 100 ml dry dichloromethane and 27.5 g carbomethoxymethylenetriphenylphospharane (83.2 mmol, 1.00 eq) prepared from carbomethoxymethylene triphenylphosphonium bromide S15

17 was added at room temperature. The solution was stirred for 5 h, concentrated on silica and purified by column chromatography (cyclohexane / EtAc = 6 / 1 + 1% NEt 3 ) to give 13.6 g methyl 4-((S)-2,2-dimethyl-1,3-dioxolan-4-yl)but-2-enoate (67.9 mmol, 83%) as colorless oil in a ratio E / Z = 88 / 12 (determined via GC-MS). R f = 0.44 (E) and 0.51 (Z) (cyclohexane / Et 2 = 1 / 1); purity 98%; [ α ] 20 = 2.1 (c = 1.36, CHCl 3 ); 1 H-NMR (500.1 MHz, CCl 3 ): δ (ppm) = 6.93 (dt, 3 J = 15.6 Hz, 3 J = 7.2 Hz, 1H, CH=CHC 2 ), 5.91 (dt, 3 J = 15.6 Hz, 3 J = 1.5 Hz, 1H, CH=CHC 2 ), 4.21 (quint, 3 J = 6.3 Hz, 1H, CH), 4.05 (dd, 2 J = 8.3 Hz, 3 J = 6.0 Hz, 1H, CH 2 CH), 3.58 (dd, 2 J = 7.9 Hz, 3 J = 6.7 Hz, 1H, CH 2 CH), 3.70 (s, 3H, ), 2.49 (dtd, 2 J = 14.8 Hz, 3 J = 6.8 Hz, 4 J = 1.4 Hz, 1H, CH 2 CH=CH), 2.41 (dtd, 2 J = 13.3 Hz, 3 J = 7.4 Hz, 4 J = 1.5 Hz, 1H, CH 2 CH=CH), 1.41 (s, 3H, ), 1.34 (s, 3H, ); 13 C-NMR (125.8 MHz, CCl 3 ): δ (ppm) = (s, C()), (d, CH=CHC 2 ), (d, CH=CHC 2 ), (s, C), 74.3 (d, CH), 68.9 (t, CH 2 CH), 51.6 (q, ), 36.6 (t, CH 2 CH=CH), 27.0 (q, ), 25.6 (q, ); GC- MS(EI): t R = 4.68 min; m / z (rel. Int. [%]): 185 (100), 169 (6), 143 (5), 125 (9), 111 (32), 101 (93), 93 (33), 83 (23), 59 (26). A solution of 13.0 g 4-((S)-2,2-dimethyl-1,3-dioxolan-4-yl)but-2-enoate (64.9 mmol, 1.00 eq) in 160 ml dry THF was cooled to 78 C. A 1 M solution of IBAH in toluene (163 ml, 163 mmol, 2.50 eq) was added over a period of 1 h. After addition had been completed the reaction mixture was quenched under cooling with a saturated sodium potassium tartrate solution (200 ml) and 1 M aqueous hydrochloric acid (carefully! ph 5). The suspension was stirred over night, the layers were separated, the aqueous phase was extracted with diethylether (3 200 ml), the combined organic layers were washed with brine, dried (MgS 4 ) and concentrated. (E)-4-((S)-2,2-imethyl-1,3-dioxolan-4-yl)but-2-en-1-ol (52) (11.1 g, 64.8 mmol, 100%) was obtained as colorless oil and used without further purification in the next step. R f = 0.25 (cyclohexane / EtAc = 1 / 1); purity = 97%; [ α ] 20 = 7.7 (c = 2.31, CHCl 3 ); 1 H-NMR (500.1 MHz, CCl 3 ): δ (ppm) = (m, 2H, CH=CH), 4.13 (quint, 3 J = 6.4 Hz, 1H, CH), 4.07 (d, 3 J = 5.3 Hz, 2H, CH 2 H), 4.00 (dd, 3 J = 8.0 Hz, 3 J = 6.0 Hz, 1H, CHCH 2 ), 3.55 (dd, 3 J = 8.0 Hz, 3 J = 7.0 Hz, 1H, CHCH 2 ), 2.34 (dt, 2 J = 13.7, 3 J = 7.2 Hz, 1H, CH 2 CH=CH), 2.23 (dt, 2 J = 13.6 Hz, 3 J = 6.5 Hz, 1H, CH 2 CH=CH), 2.10 (br, 1H, H), 1.39 (s, 3H, ), 1.32 (s, 3H, ); 13 C-NMR (125.8 MHz, CCl 3 ): δ (ppm) = (d, CH=CHCH 2 H), (d, CH=CHCH 2 H), (s, C), 75.3 (d, CH), 68.9 (t, CHCH 2 ), 63.3 (t, CH 2 H), 36.6 (t, CH 2 CH=CH), 26.9 (q, ), S16

18 25.6 (q, ); GC-MS(EI): t R = 4.11 min; m / z (rel. Int. [%]): 157 (1), 145 (40), 127 (13), 115 (100), 99 (14), 89 (48), 85 (31), 75 (59), 59 (28). (S)-2,2-imethyl-4-(pent-4-ynyl)-1,3-dioxolane (53): To 10.7 g (E)-4-((S)-2,2-dimethyl-1,3- dioxolan-4-yl)but-2-en-1-ol (52) (62.2 mmol, 1.00 eq) dissolved in 200 ml dichloromethane 119 g manganese(ii) oxide (1.37 mol, 22.0 eq) was added at 0 C. The suspension was stirred for 90 min at room temperature and was filtered throug celite. Concentration of the eluent gave 8.47 g (E)-4-((S)-2,2-dimethyl-1,3-dioxolan-4-yl)but-2-enal (49.7 mmol, 80%) as yellow oil that was used without further purification in the next step. R f = 0.46 (cyclohexane / EtAc = 1 / 1); purity 98%; [ α ] 20 = 18.6 (c = 0.78, CHCl 3 ); 1 H-NMR (500.1 MHz, CCl 3 ): δ (ppm) = 9.51 (d, 3 J = 8.0 Hz, 1H, CH()), 6.84 (dt, 3 J = 15.7 Hz, 3 J = 7.0 Hz, 1H, CH=CHCH()), 6.18 (dd, 3 J = 15.7 Hz, 3 J = 7.7 Hz, 1H, CH=CHCH()), 4.26 (quint, 3 J = 6.2 Hz, 1H, CH), 4.08 (dd, 2 J = 8.2 Hz, 3 J = 6.0 Hz, 1H, CH 2 ), 3.59 (dd, 2 J = 8.2 Hz, 3 J = 6.5 Hz, 1H, CH 2 ), 2.58 (td, 3 J = 6.9 Hz, 4 J = 1.3 Hz, 2H, CH 2 CH=CH), 1.41 (s, 3H, ), 1.34 (s, 3H, ); 13 C-NMR (125.8 MHz, CCl 3 ): δ (ppm) = (d, CH()), (d, CH=CHCH()), (d, CH=CHCH()), (s, C), 73.9 (d, CH), 68.7 (t, CH 2 ), 36.8 (t, CH 2 CH=CH), 26.8 (q, ), 25.4 (q, ); GC-MS(EI): t R = 4.29 min; m / z (rel. Int. [%]): 155 (100), 113 (1), 101 (52), 95 (11), 83 (16), 81 (7), 73 (13), 67 (64), 59 (13). (E)-4-((S)-2,2-imethyl-1,3-dioxolan-4-yl)but-2-enal (8.47 g, 49.7 mmol, 1.00 eq) was dissolved in 100 ml ethyl acetate and 2.65 g palladium hydroxide on carbon (20% Pd on carbon, 4.97 mmol, 0.10 eq) was added. Hydrogen was bubbled through the suspension for 10 min and the mixture was stirred for 3.5 h at room temperature under hydrogen atmosphere. The suspension was filtrated over celite. Concentration of the eluent gave 8.44 g 4-((S)-2,2- dimethyl-1,3-dioxolan-4-yl)butanal (49.0 mmol, 99%) as colorless oil that was used without further purification in the next step. R f = 0.63 (cyclohexane / EtAc = 1 / 1); purity = 95%; [ α ] 20 = 16.1 (c = 0.71, CHCl 3 ) (lit. [12] : 16.0 ); 1 H-NMR (500.1 MHz, CCl 3 ): δ (ppm) = 9.76 (t, 3 J = 1.6 Hz, 1H, CH()), (m, 2H, CH 2 ), 3.51 (t, 3 J = 7.3 Hz, 1H, CH), 2.49 (tt, 3 J = 7.2 Hz, 4 J = 1.2 Hz, 2H, CH 2 CH()), (m, 4H, CH 2 CH 2 CH 2 CH()), 1.39 (s, 3H, ), 1.33 (s, 3H, ); 13 C-NMR (125.8 MHz, CCl 3 ): δ (ppm) = (d, CH()), (s, C), 75.7 (d, CH), 69.4 (t, CH 2 ), 43.7 (t, CH 2 CH()), 33.0 (t, CH 2 CH 2 CH 2 CH()), 27.0 (q, ), 25.8 (q, ), 18.5 (t, S17

19 CH 2 CH 2 CH()); GC-MS(EI): t R = 4.08 min; m / z (rel. Int. [%]): 157 (100), 129 (1), 115 (1), 97 (29), 83 (5), 79 (44), 72 (46), 67 (21), 59 (18). n-buthyllithium (2.15 M, 26.5 ml, 60.0 mmol, 1.20 eq) was added dropwise at 78 C to a solution of 9.4 ml diisopropylamine (66.5 mmol, 1.40 eq) in 150 ml dry THF, [13] immediately followed by 30.0 ml 1-(trimethylsilyl)diazomethane (60.0 mmol, 1.20 eq) at 78 C. After 30 min stirring at 78 C 8.17 g 4-((S)-2,2-dimethyl-1,3-dioxolan-4-yl)butanal (47.5 mmol, 1.00 eq) in 40 ml dry THF added dropwise to the yellow solution. After further 60 min stirring at 78 C the dark brown reaction mixture was warmed up slowly to room temperature and was refluxed for 60 min. After the solution has cooled to room temperature water was added (200 ml) and the biphasic mixture was separated. The aqueous layer was extracted with diethylether (3 100 ml), the combined organic layers were washed with brine (200 ml), dried (MgS 4 ) and concentrated. The brown oil was purified by column chromatography (cyclohexane / Et 2 = 9 / 1 + 1% NEt 3 ) to yield 6.03 g (S)-2,2-dimethyl-4- (pent-4-ynyl)-1,3-dioxolane (53) (35.9 mmol, 75%) as colorless oil. R f = 0.19 (cyclohexane / Et 2 = 9 / 1); purity 98%; [ α ] 20 = 12.6 (c = 0.78, CHCl 3 ); S18 1 H-NMR (500.1 MHz, CCl 3 ): δ (ppm) = 4.09 (quint, 3 J = 6.2 Hz, 1H, CH), 4.03 (dd, 3 J = 7.7 Hz, 3 J = 6.0, 1H, CH 2 ), 3.51 (t, 3 J = 7.5 Hz, 1H, CH 2 ), (m, 2H, CH 2 C CH), 1.94 (t, 4 J = 2.6 Hz, C CH), (m, 4H, CH 2 CH 2 CH 2 C CH), 1.39 (s, 3H, ), 1.34 (s, 3H, ); 13 C-NMR (125.8 MHz, CCl 3 ): δ (ppm) = (s, C), 83.9 (s, C CH), 75.5 (d, CH), 69.3 (t, CH 2 ), 68.6 (d, C CH), 32.5 (t, CH 2 CH 2 CH 2 C CH), 26.9 (q, ), 25.6 (q, ), 24.7 (t, CH 2 CH 2 C CH), 18.3 (t, CH 2 C CH); GC-MS(EI): t R = 3.74 min; m / z (rel. Int. [%]): 153 (100), 126 (1), 111 (8), 93 (81), 77 (68), 72 (56), 59 (18), 53 (13). 2-((R)-4-thylhex-5-ynyloxy)-tetrahydro-2H-pyran (56): ( )-β-citronellene (54) (50.0 ml, 275 mmol, 1.00 eq) was dissolved in 600 ml dichloromethane and cooled to 78 C. zone was bubbled through the solution and reaction was monitored by TLC. After starting material had disappeared argon was bubbled through the solution, the mixture was brought to room temperature and was concentrated. The residue was dissolved in 300 ml dry methanol and at 0 C 15.6 g sodium borohydride (413 mmol, 1.50 eq) was added portion-wise over a period of 20 min followed by stirring at room temperature for 60 min. Half of the methanol was evaporated and the reaction was quenched with aqueous saturated ammonium chloride solution. The biphasic mixture was separated, the aqueous layer was extracted with diethylether (4 250 ml), the combined organic layers were washed with brine (300 ml), dried (MgS 4 ) and concentrated. Purification was achieved by column chromatography

20 (cyclohexane / EtAc = 6 / 1) to yield 28.6 g (R)-4-methylhex-5-en-1-ol (55) (250 mmol, 91%) as colorless liquid. R f = 0.20 (cyclohexane / EtAc = 6 / 1); purity 98%; [ α ] 20 = 9.9 (c = 1.25, CHCl 3 ) (lit. [14] : 7.9 ); ee 98% (determined via chiral GC); 1 H-NMR (500.1 MHz, CCl 3 ): δ (ppm) = 5.67 (ddd, 3 J = 17.4 Hz, 3 J = 7.5 Hz, 3 J = 10.0 Hz, 1H, CH=CH 2 ), 4.94 (d, 3 J = 17.2 Hz, 1H, CH=CH 2 ), 4.90 (d, 3 J = 10.2 Hz, 1H, CH=CH 2 ),3.60 (t 3 J = 6.7 Hz, 2H, CH 2 H), 2.11 (sept, 3 J = 7.0 Hz, 1H, CH), 1.88 (br, 1H, H), (m, 2H, CH 2 CH 2 H), (m, 2H, CH 2 CH 2 CH 2 H), 0.98 (d, 3 J = 6.7 Hz, 3H, ); 13 C-NMR (125.8 MHz, CCl 3 ): δ (ppm) = (d, CH=CH 2 ), (t, CH=CH 2 ), 63.1 (t, CH 2 H), 37.7 (d, CH), 32.7 (t, CH 2 CH 2 CH 2 H), 30.6 (t, CH 2 CH 2 H), 20.3 (q, ); GC- MS(EI): t R = 2.88 min; m / z (rel. Int. [%]): 96 (6), 95 (5), 81 (100), 79 (21), 70 (58), 68 (62), 57 (25), 55 (96), 53 (30). To a solution of 16.6 g (R)-4-methylhex-5-en-1-ol (55) (145 mmol, 1.00 eq) and 17.8 ml 3,4- dihydro-2h-pyran (196 mmol, 1.35 eq) in 140 ml dry dichloromethane 827 mg p- toluenesulfonic acid (4.35 mmol, 0.03 eq) was added at room temperature and stirring continued for 3 h. Triethylamine (880 mg, 8.70 mmol, 0.06 eq) was added, the solution was concentrated and the residue filtrated over a silica plug (cyclohexane / EtAc = 9 / 1) to give 27.2 g 2-((R)-4-methylhex-5-enyloxy)-tetrahydro-2H-pyran (138 mmol, 95%) as colorless liquid. R f = 0.49 (cyclohexane / Et 2 = 9 / 1); purity = 96%; [ α ] 20 = 4.5 (c = 2.64, CHCl 3 ); 1 H-NMR (500.1 MHz, CCl 3 ): δ (ppm) = 5.67 (ddd, 3 J = 17.3 Hz, 3 J = 10.1 Hz, 3 J = 7.4 Hz, 1H, CH=CH 2 ), (m, 2H, CH=CH 2 ), 4.56 (t, 3 J = 3.5 Hz, 1H, CH), (m, 1H), 3.70 (dt, 3 J = 9.5 Hz, 3 J = 7.0 Hz, 1H), (m, 1H), 3.36 (dt, 3 J = 9.4 Hz, 3 J = 6.8 Hz, 1H), 2.12 (sept, 3 J = 6.9 Hz, 1H, CH), (m, 8H), (m, 2H), 0.98 (d, 3 J = 6.7 Hz, 3H, ); 13 C-NMR (125.8 MHz, CCl 3 ): δ (ppm) = (d, CH=CH 2 ), (t, CH=CH 2 ), 98.9 (d, CH), 67.8 (t, CH 2 THP), 62.4 (t, CH 2 ), 37.8 (d, CH), 33.2 (t), 30.9 (t), 27.6 (t), 25.6 (t), 20.3 (q, ), 19.8 (t); GC-MS(EI): so51141: R f = (cyclohexane / EtAc=); GC-MS(EI): t R = 4.63 min; m / z (rel. Int. [%]): 112 (2), 111 (2), 101 (12), 97 (21), 85 (100), 81 (14), 67 (17), 55 (62). 2-((R)-4-thylhex-5-enyloxy)-tetrahydro-2H-pyran (3.97 g, 20.0 mmol, 1.00) was dissolved in 30 ml dry dichloromethane. A solution of 1.13 ml bromine (22.0 mmol, 1.10 eq) in 10 ml dry dichloromethane was added dropwise at 78 C. After 5 min the reaction was finished and quenched with aqueous saturated sodium thiosulfate solution (20 ml). The biphasic mixture was separated, the aqueous layer was extracted with dichloromethane (3 50 ml), the S19