Supporting Information

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1 Supporting Information Enantiospecific Synthesis of the Cubitane Skeleton Elisabeth Schöttner, M. Wiechoczek, Peter G. Jones, and Thomas Lindel * TU Braunschweig, Institutes of rganic, Inorganic and Analytical Chemistry, agenring 30, Braunschweig, Germany th.lindel@tu-bs.de Content 1. Eperimental procedures and 13 C NMR spectra NESY correlations of diol 20 35

2 1 1. Eperimental procedures Synthesis of 5: General methods: NMR spectra were taken with a Bruker DRX-400 (400.1 Mz for 1, Mz for 13 C), a Bruker AV III-400 (400.1 Mz für 1, Mz für 13 C) and a Bruker AV II- 600 (600.1 Mz for 1 ; Mz for 13 C), referenced to solvent signal or. All measurements were carried out at 300 K. Mass spectra were obtained with a LTQ rbitrap Velos, a Thermo Finnigan LTQ FT, a Thermo Finnigan MAT95 and a Finnigan MAT 95 XLT spectrometer. IR spectra were recorded with a Bruker Tensor 27 spectrometer. UV/Vis spectra were measured with a Varian Cary 100 Bio UV/Vis-spectrometer. ptical rotations were measured on a Dr. Kernchen Propol Automatic Polarimeter. Melting points were measured with a Büchi 530 melting point apparatus. Chemicals were purchased from commercial suppliers and used without further purification. Silica gel 60 (40-63 µm, Merck) was used for column chromatography. (2S,3R,6S)-2-[(R,E)-1-((tert-Butyldimethylsilyl)oy)-4-hydroy-2-methylbut-2-en- 1-yl]-3-isopropyl-6-methylcycloheanone (5b) (2S,3R,6R)-2-[(R,E)-1-((tert-Butyldimethylsilyl)oy)-4-hydroy-2-methylbut-2-en- 1-yl]-3-isopropyl-6-methylcycloheanone (5c) To a solution of alcohol 5a 1 ( g, 2.73 mmol, equiv) in TF (22 ml) was added at -78 C K-Selectride (1 M in TF, 8.2 ml, 8.2 mmol, 3.00 equiv) and the solution was stirred for 2.5 h at -78 C and then for 20 h at -40 C. Aqueous 2 M Na (32 ml) was carefully added and after warming to 0 C 2 2 (30%, 16 ml) was added slowly. The solution was diluted with PE and stirred for 30 min. The aqueous phase was etracted with PE/EA (1:1) (3), the combined organic layers were dried over MgS 4, filtered and the solvent was evaporated. After column chromatography on silica [PE:EA: (6:1)] 5b (692 mg, 1.88 mmol, 69%) was obtained as colorless oil together with diastereomer 5c (163 mg, 0.44 mmol, 16%) as colorless 1 For synthesis of 5a see: Schöttner, E.; Jones, P. G.; Lindel, T. Synthesis 2009,

3 2 crystals. 2 Diastereomer 5b: TLC [silica, PE/EA: (6:1)]: R f = [ α ] 23 D 20.7 (c 1.51, CCl 3 ). 1 NMR (300 Mz, CDCl 3 ): δ = 0.00 [s, 3, Si(C 3 )], 0.04 [s, 3, Si(C 3 )], 0.83 [d, 3 J = 6.9 z, 3, C(C 3 ) 2 ], 0.85 [d, 3 J = 7.0 z, 3, C(C 3 ) 2 ], 0.90 [s, 9, SiC(C 3 ) 3 ], 1.08 (d, 3 J = 6.8 z, 3, CCC 3 ), (m, 2, CCC 2 C 2, CCC 2 C 2 ), 1.52 [s, 3, C(Si)CC 3 ], (m, 1, CCC 2 C 2 ), (m, 1, CCC 2 C 2 ), (m, 1, CCC 2 C 2 ), [m, 1, C(C 3 ) 2 ], (m, 1, CCC 3 ), (m, 1, CCC 2 C 2 ), 4.21 (d, 3 J = 6.8 z, 2, C 2 ), 4.91 [s, 1, C(Si)CC 3 ], (m, 1, CC 2 ). 13 C NMR (75 Mz, CDCl 3 ): δ = -5.1 [Si(C 3 )], -4.7 [Si(C 3 )], 14.2 [C(Si)CC 3 ], 15.8 (CCC 3 ), 16.3 [C(C 3 ) 2 ], 18.0 [SiC(C 3 ) 3 ], 21.1 [C(C 3 ) 2 ], 22.8 (CCC 2 C 2 ), 25.9 [3C, SiC(C 3 ) 3 ], 28.0 [C(C 3 ) 2 ], 31.9 (CCC 2 C 2 ), 44.9 (CCC 2 C 2 ), 45.1 (CCC 3 ), 58.1 (CCC 2 C 2 ), 59.1 (CC 2 ), 74.8 [C(Si)CC 3 ], (CC 2 ), [C(Si)CC 3 ], (C). MS (ESI): m/z (%) = 391/392 (100/27) [M+Na] +. IR (ATR): ν ~ = 3435 (br), 2955 (m), 2931 (m), 2858 (m), 1700 (m), 1461 (w), 1386 (w), 1365 (w), 1253 (m), 1089 (m), 1053 (s), 1006 (m), 879 (m), 836 (s), 811 (m), 744 (s), 680 (w), 667 (w). UV (Me): λ ma (lg ε) = 203 (3.82), 240 (2.69). RESIMS calcd. for C SiNa [M+Na] + : , found Diastereomer 5c: TLC [silica, PE/EA: (6:1)]: R f = [ α ] 23 D (c 1.11, CCl 3 ). 1 NMR (400 Mz, CDCl 3 ): δ = [s, 3, Si(C 3 )], 0.01 [s, 3, Si(C 3 )], 0.81 [s, 9, SiC(C 3 ) 3 ], 0.82 [d, 3 J = 6.6 z, 3, C(C 3 ) 2 ], 0.88 [d, 3 J = 6.4 z, 3, C(C 3 ) 2 ], 0.99 (d, 3 J = 6.4 z, 3, CCC 3 ), (m, 1, CCC 2 C 2 ), [m, 2, CCC 2 C 2, C(C 3 ) 2 ], [s, 3, C(Si)CC 3 ], (m, 1, CCC 2 C 2 ), 1.85 (td, 3 J = 4.2 z, 2 J = 13.8 z, 1, CCC 2 C 2 ), (m, 1, CCC 2 C 2 ), (m, 1, CCC 3 ), 2.69 (d, 3 J = 10.3, 1, CCC 2 C 2 ), (m, 2, C 2 ), 4.53 [d, 3 J = 10.2, 1, C(Si)CC 3 ], (m, 1, CC 2 ). 2 X-ray crystal structure files for compound 5c in CIF format available

4 3 13 C NMR (100 Mz, CDCl 3 ): δ = -5.5 [Si(C 3 )], -4.4 [Si(C 3 )], 10.3 [C(Si)CC 3 ], 14.5 (CCC 3 ), 17.9 [SiC(C 3 ) 3 ], 20.4 [C(C 3 ) 2 ], 21.4 [C(C 3 ) 2 ], 22.9 (CCC 2 C 2 ), 25.5 [3C, SiC(C 3 ) 3 ], 27.3 [C(C 3 ) 2 ], 32.1 (CCC 2 C 2 ), 41.9 (CCC 3 ), 45.7 (CCC 2 C 2 ), 57.7 (CCC 2 C 2 ), 59.1 (CC 2 ), 79.6 [C(Si)CC 3 ], (CC 2 ), [C(Si)CC 3 ], (C). MS (ESI): m/z (%) = 391/392 (100/24) [M+Na] +. IR (ATR): ν ~ = 3439 (br), 2957 (m), 2930 (m), 2888 (m), 2859 (m), 1703 (m), 1462 (m), 1387 (w), 1364 (w), 1251 (m), 1158 (w), 1089 (m), 1058 (s), 1006 (m), 964 (w), 866 (m), 836 (s), 809 (w), 744 (s), 733 (w), 666 (w), 587 (w), 537 (w). UV (Me): λ ma (lg ε) = 203 (3.86). RESIMS calcd. for C SiNa [M+Na] + : , found M.p.: C. (R,E)-4-[(tert-Butyldimethylsilyl)oy]-4-[(1S,3S,6R)-6-isopropyl-3-methyl-2- oocycloheyl]-3-methylbut-2-en-1-yl diethyl phosphate (5) TBS ClP(Et) 2, pyridine, DCM, 0 C, 3 h, 53% TBS P 5b 5 Alcohol 5b (790 mg, 2.15 mmol, equiv) was dissolved under nitrogen in dry DCM (6.0 ml) and pyridine (0.21 ml, 2.58 mmol, 1.20 equiv) and diethyl chlorophosphate (0.41 ml, 2.80 mmol, 1.30 equiv) were added at 0 C. The miture was stirred for 3.0 h at 0 C and then quenched with aqueous 2 M Cl. The aqueous phase was etracted with Et 2 (3) and the combined organic phases were dried over MgS 4 and filtered. After evaporation of the solvent, the residue was purified by column chromatography on silica [PE/EA: (2:1)]. 5 (570 mg, 1.13 mmol, 53%) was obtained as colorless oil. TLC [silica, PE/EA: (2:1)]: R f = [ α ] 23 D 80.1 (c 1.11, CCl 3 ). 1 NMR (400 Mz, CDCl 3 ): δ = [s, 3, Si(C 3 )], 0.01 [s, 3, Si(C 3 )], 0.81 [s, 9, SiC(C 3 ) 3 ], 0.81 [d, 3 J = 6.5 z, 3, C(C 3 ) 2 ], 0.87 [d, 3 J = 6.4 z, 3, C(C 3 ) 2 ], 0.99 (d, 3 J = 6.4 z, 3, CCC 3 ), (m, 1, CCC 2 C 2 ), 1.35 (dt, 3 J = 7.1 z, 4 J = 0.9 z, 6, PC 2 C 3 ), [m, 2, CCC 2 C 2, C(C 3 ) 2 ], 1.62 (s, 3, C(Si)CC 3 ], (m, 1, CCC 2 C 2 ), (m, 2, CCC 2 C 2, CCC 2 C 2 ), (m, 1, CCC 3 ), 2.68 (d,

5 4 3 J = 10.4 z, 1, CCC 2 ), (m, 4, PC 2 C 3 ), 4.54 [d, 3 J = 10.3 z, 1, C(Si)CC 3 ], (m, 2, CC 2 P), 5.64 (dt, 3 J = 6.6 z, 4 J = 1.2 z, 1, CC 2 P). 13 C NMR (100 Mz, CDCl 3 ): δ = -5.5 [Si(C 3 )], -4.4 [Si(C 3 )], 10.4 [C(Si)CC 3 ], 14.5 (CCC 3 ), 16.1 (d, 3 J = 10.2 z, 2C, PC 2 C 3 ), 17.9 [SiC(C 3 ) 3 ], 20.4 [C(C 3 ) 2 ], 21.3 [C(C 3 ) 2 ], 23.0 (CCC 2 ), 25.5 [3C, SiC(C 3 ) 3 ], 27.3 [C(C 3 ) 2 ], 32.1 (CCC 2 C 2 ), 41.9 (CCC 3 ), 45.6 (CCC 2 ), 57.7 (CCC 2 ), 63.3 (d, 2 J = 5.4 z, CC 2 P), 63.8 (d, 2 J = 5.8 z, 2C, PC 2 C 3 ), 79.3 [C(Si)CC 3 ], (d, 3 J = 7.3 z, CC 2 P), [C(Si)CC 3 ], (C). MS (ESI): m/z (%) = 527/528 (100/53) [M+Na] +. IR (ATR): ν ~ = 2958 (m), 2931 (m), 2892 (w), 2859 (w), 1710 (m), 1463 (w), 1389 (w), 1257 (m), 1161 (w), 1095 (m), 1064 (s), 1029 (s), 998 (s), 858 (m), 836 (s), 809 (m), 775 (s), 666 (w), 589 (w), 535 (w). UV (Me): λ ma (lg ε) = 203 (2.10), 290 (3.89). RESIMS calcd. for C SiPNa [M+Na] + : , found (1R,2R,3E,7E,10R,11S,12S,13R)-13-Isopropyl-3,7,11-trimethylbicyclo[8.2.2]tetradeca-3,7-diene-2,12-diol (9) To a solution of isoeunicellane 4 3 (20 mg, mmol, equiv) in TF (4.0 ml) was added DIBAl- (25% in toluene, 0.45 ml, 14.0 equiv) and the miture was heated under reflu for 2.0 h. After cooling to rt, water and 2 M Cl was added and the aqueous phase was etracted with Et 2 (3). To the aqueous phase was added 2 M Na and etracted again with Et 2 (2). The combined 9 organic phases were dried over MgS 4, filtered and evaporated. The crude residue was purified by column chromatography on silica [PE/EA (5:1)] to obtain diol 9 (13.9 mg, mmol, 94%) as colorless solid. TLC [silica, PE/EA: (5:1)]: R f = [ α ] 23 D (c 1.39, CCl 3 ). 1 NMR (600 Mz, CDCl 3 ): δ = 0.87 [d, 3 J = 6.7 z, 3, C(C 3 ) 2 ], 0.93 [d, 3 J = 6.7 z, 3, C(C 3 ) 2 ], 1.02 (d, 3 J = 7.1 z, 3, CCC 3 ), (m, 1, CCCC 2 ), 1.59 (s, 3, C 2 C 2 CC 3 ), [m, 2, CCCC 2, 3 For synthesis of 4 see: Schöttner, E.; Jones, P. G.; Lindel, T. Synthesis 2009,

6 5 C()C], 1.69 [d, 3 J = 12.6 z, 1, C()CC 3 ], 1.78 (d, 3 J = 1.1 z, 3, C 2 C 2 CCC 3 ), (m, 2, CCC 3, CCCC 2 ), [m, 2, C 3 CCC 2 C, C(C 3 ) 2 ], (m, 1, C 3 CCC 2 C), (m, 3, CCCC 2, C 2 C 2 CC 3, C 2 C 2 CC 3 ), (m, 2, C 3 CCC 2 C, C 2 C 2 CC 3 ), (m, 1, C 2 C 2 CC 3 ), 3.77 [ddd, 3 J = 4.3 z, 3 J = 8.3 z, 3 J = 12.6 z, 1, C()CC 3 ], 4.88 (s, 1, C()C), 5.28 (m, 1, C 3 CCC 2 C), 5.69 (dd, 3 J = 5.8 z, 3 J = 10.0 z, 1, CC 2 C 2 C). 13 C NMR (150 Mz, CDCl 3 ): δ = 14.0 (C 3 CCC 2 C 2 ), 15.4 (C 3 CCC 2 C), 15.9 [C()CC 3 ], 18.2 [C(C 3 ) 2 ], 21.8 [C(C 3 ) 2 ], 24.6 (C 2 C 2 CC 3 ), 25.7 (CCCC 2 ), 26.4 (C 3 CCC 2 C), 30.5 [C(C 3 ) 2 ], 33.8 (C 3 CCC 2 C), 36.3 (CCCC 2 ), 36.7 [C()CC 3 ], 40.2 (C 2 C 2 CC 3 ), 48.2 (CCCC 2 ), 72.3 [C()CC 3 ], 77.5 [C()C], (C 3 CCC 2 C), (C 3 CCC 2 C 2 ), (C 2 C 2 CC 3 ), (C 3 CCC 2 C 2 ). MS (ESI): m/z (%) = 329/330 (100/21) [M+Na] +. IR (ATR): ν ~ = 3527 (m), 3434 (m), 2958 (m), 2915 (m), 2863 (m), 1434 (m), 1382 (m), 1347 (w), 1156 (w), 1115 (w), 1057 (m), 1016 (s), 963 (m), 938 (w), 903 (m), 821 (w), 785 (w), 766 (w), 661 (m), 599 (s), 580 (s). UV (Me): λ ma (lg ε) = 204 (3.97). RESIMS calcd. for C Na [M+Na] + : , found M. p.: C. (1R,3E,7E,9R,10S,12R,14R)-9-[(tert-Butyldimethylsilyl)oy]-12-hydroperoy-14- isopropyl-4,8,12-trimethylbicyclo[8.2.2]tetradeca-3,7-dien-11-one (10) TBS 10 Isoeunicellane 4 (15 mg, mmol, equiv) was dissolved in TF (3.0 ml) and cooled to -40 C. LiAl 4 (4 M in Et 2, 0.03 ml, 0.12 mmol, 3.33 equiv) was added under air and the solution was slowly warmed to -20 C. After stirring for 4.0 h at -20 C water was carefully added. The aqueous phase was etracted with Et 2 (3) and the combined organic phases were washed with brine and dried over MgS 4. The residue obtained after evaporation of the solvent was purified by column chromatography on silica [PE/EA (10:1)] to give hydroperoide 10 (10 mg, mmol, 64%) as colorless oil. TLC [silica, PE/EA: (10:1)]: R f = [ α ] 23 D (c 1.42, CCl 3 ). 1 NMR (400 Mz, CDCl 3 ): δ = 0.02 [s, 3, Si(C 3 )], 0.02 [s, 3, Si(C 3 )],

7 6 [m, 15, SiC(C 3 ) 3, C(C 3 ) 2, C(C 3 ) 2 ], (m, 1, CCCC 2 ), 1.47 [s, 3, C()C 3 ], 1.55 (s, 3, C 2 C 2 CC 3 ), 1.63 (s, 3, C 2 C 2 CCC 3 ), (m, 2, C 2 C 2 CC 3, C 2 C 2 CC 3 ), (m, 3, CCCC 2, CCCC 2, C 2 C 2 CC 3 ), (m, 3, C 3 CCC 2 C, C 3 CCC 2 C), (m, 1, C 2 C 2 CC 3 ), [m, 1, C(C 3 ) 2 ], (m, 1, CCCC 2 ), (m, 1, C 3 CCC 2 C), 5.18 (tdd, 3 J = 2.8 z, 3 J = 11.6 z, 4 J = 1.3 z, 1, CC 2 C 2 C), 5.59 (s, 1, CCCC 2 ), 7.48 [s, 1, C()C 3 ]. 13 C NMR (100 Mz, CDCl 3 ): δ = -5.4 [Si(C 3 )], -5.1 [Si(C 3 )], 13.1 (C 3 CCC 2 C 2 ), 15.3 [C(C 3 ) 2 ], 15.3 (C 3 CCC 2 C), 16.8 [C()C 3 ], 18.1 [SiC(C 3 ) 3 ], 21.2 [C(C 3 ) 2 ], 24.7 (C 2 C 2 CC 3 ), 24.7 (CCCC 2 ), 25.9 [3C, SiC(C 3 ) 3 ], 27.5 [C(C 3 ) 2 ], 30.8 (C 3 CCC 2 C), 39.4 (CCCC 2 ), 40.0 (C 2 C 2 CC 3 ), 42.8 (C 3 CCC 2 C), 59.0 (CCCC 2 ), 73.0 (CCCC 2 ), 87.8 [C()C 3 ], (C 3 CCC 2 C), (C 3 CCC 2 C 2 ), (C 2 C 2 CC 3 ), (C 3 CCC 2 C 2 ), (C). MS (ESI): m/z (%) = 473/474 (100/32) [M+Na] +. IR (ATR): ν ~ = 3404 (br), 2953 (m), 2929 (m), 2856 (m), 1707 (m), 1463 (w), 1387 (w), 1372 (w), 1253 (m), 1098 (m), 1070 (s), 1043 (s), 1016 (s), 904 (w), 885 (s), 863 (s), 774 (s), 674 (w), 587 (m). UV (Me): λ ma (lg ε) = 204 (3.89). RESIMS calcd. for C SiNa [M+Na] + : , found Reductions of 10: (1R,3E,7E,9R,10S,12R,14R)-9-[(tert-Butyldimethylsilyl)oy]-12-hydroy-14- isopropyl-4,8,12-trimethylbicyclo[8.2.2]tetradeca-3,7-dien-11-one (10a) ydroperoide 10 (8 mg, mmol, equiv) was dissolved in TF (2.0 ml) and NaI (14 mg, mmol, 5.33 equiv) was added at rt. The reaction miture changed TBS immediately after adding NaI the color to yellow. After stirring for 5 min, the miture was diluted with water and etracted with Et 2 (3). The combined organic layers 10a were dried over MgS 4, filtered and evaporated. The crude residue was purified by column chromatography on silica [PE/EA (10:1)] to obtain alcohol 10a (3.9 mg, mmol, 51%) as colorless oil. TLC [silica, PE/EA: (10:1)]: R f = 0.31.

8 7 [ α ] 23 D (c 0.39, CCl 3 ). 1 NMR (600 Mz, CDCl 3 ): δ = 0.00 [s, 3, Si(C 3 )], 0.02 [s, 3, Si(C 3 )], 0.86 [d, 3 J = 6.7 z, 3, C(C 3 ) 2 ], 0.87 [s, 9, SiC(C 3 ) 3 ], 0.89 [d, 3 J = 7.1 z, 3, C(C 3 ) 2 ], (m, 1, CCCC 2 ), 1.44 (s, 3, C 3 C), 1.55 (s, 3, C 2 C 2 CC 3 ), 1.62 (s, 4, C 2 C 2 CCC 3, C 3 C), (m, 4, C 3 CCC 2 C, C 2 C 2 CC 3, CCCC 2 ), (m, 4, CCCC 2, C 3 CCC 2 C, C 3 CCC 2 C), (m, 1, C 3 CCC 2 C), [m, 1, C(C 3 ) 2 ], 2.89 (dd, 3 J = z, 3 J = 11.1 z, 1, CCCC 2 ), 4.79 (t, 3 J = 7.4 z, 1, C 3 CCC 2 C), (m, 1, CC 2 C 2 C), 5.59 (s, 1, CCCC 2 ). 13 C NMR (150 Mz, CDCl 3 ): δ = -5.3 [Si(C 3 )], -5.1 [Si(C 3 )], 13.1 (C 3 CCC 2 C 2 ), 15.0 [C(C 3 ) 2 ], 15.3 (C 3 CCC 2 C), 18.0 [SiC(C 3 ) 3 ], 21.1 [C(C 3 ) 2 ], 23.0 (C 3 C), 24.7 (C 2 C 2 CC 3 ), 24.9 (CCCC 2 ), 25.9 [3C, SiC(C 3 ) 3 ], 27.2 [C(C 3 ) 2 ], 30.6 (C 3 CCC 2 C), 38.8 (CCCC 2 ), 39.9 (C 2 C 2 CC 3 ), 45.3 (C 3 CCC 2 C), 57.8 (CCCC 2 ), 73.1 (CCCC 2 ), 76.2 (C 3 C), (C 3 CCC 2 C), (C 3 CCC 2 C 2 ), (C 2 C 2 CC 3 ), (C 3 CCC 2 C 2 ), (C). MS (ESI): m/z (%) = 457/458 (100/32) [M+Na] +. IR (ATR): ν ~ = 3463 (br), 2953 (m), 2929 (m), 2856 (m), 1703 (m), 1463 (w), 1386 (w), 1253 (m), 1064 (s), 1042 (s), 1012 (m), 934 (m), 913 (s), 887 (s), 854 (w), 834 (s), 774 (s), 757 (s), 677 (w), 666 (w), 568 (w). UV (Me): λ ma (lg ε) = 202 (3.77). RESIMS calcd. for C SiNa [M+Na] + : , found (1R,2R,3E,7E,10R,11R,12R,13R)-2-[(tert-Butyldimethylsilyl)oy]-13-isopropyl- 3,7,11-trimethylbicyclo[8.2.2]tetradeca-3,7-diene-11,12-diol (10b) 10b TBS Isoeunicellane 4 (10 mg, mmol, equiv) was dissolved in TF (3.0 ml) and cooled to -40 C. LiAl 4 (4 M in Et 2, 0.03 ml, 0.12 mmol, 5.00 equiv) was added. The miture was allowed to warm to rt over 16 h. After 3 d stirring at rt, water was added and the aqueous phase was etracted with Et 2 (3). The combined organic phases were washed with brine, dried over MgS 4 and filtered. The residue obtained after evaporation of the solvent was purified by column chromatography on silica [PE/EA (8:1)] to obtain diol 10b (6 mg, mmol, 58%) as colorless oil. TLC [silica, PE/EA: (10:1)]: R f = 0.14.

9 8 [ α ] 23 D (c 1.10, CCl 3 ). 1 NMR (400 Mz, CDCl 3 ): δ = [s, 3, Si(C 3 )], 0.04 [s, 3, Si(C 3 )], 0.82 [d, 3 J = 6.7 z, 3, C(C 3 ) 2 ], 0.87 [s, 9, SiC(C 3 ) 3 ], 0.93 [d, 3 J = 7.1 z, 3, C(C 3 ) 2 ], 1.05 (s, 1, C 3 C), 1.38 (s, 3, C 3 C), (m, 1, CCCC 2 ), 1.56 (s, 3, C 2 C 2 CC 3 ), 1.74 (s, 3, C 2 C 2 CCC 3 ), (m, 3, C 3 CCC 2 C, CCCC 2, CCCC 2 ), (m, 5, CCCC 2, C 3 CCC 2 C, C 2 C 2 CC 3, C 2 C 2 CC 3 ), (m, 1, C 2 C 2 CC 3 ), [m, 2, C 3 CCC 2 C, C(C 3 ) 2 ], 2.51 (d, 3 J = 12.0 z, 1, C), 3.46 (dd, 3 J = 6.3 z, 3 J = 12.0 z, 1, C), 4.73 (s, 1, CCCC 2 ), 5.50 (m, 1, C 3 CCC 2 C), (m, 1, CC 2 C 2 C). 13 C NMR (100 Mz, CDCl 3 ): δ = -5.2 [Si(C 3 )], -5.1 [Si(C 3 )], 13.7 (C 3 CCC 2 C 2 ), 14.7 (C 3 CCC 2 C), 14.8 [C(C 3 ) 2 ], 18.0 [SiC(C 3 ) 3 ], 20.5 (CCCC 2 ), 21.1 [C(C 3 ) 2 ], 23.9 (C 2 C 2 CC 3 ), 25.8 [3C, SiC(C 3 ) 3 ], 26.5 (C 3 C), 28.7 (C 3 CCC 2 C), 29.0 [C(C 3 ) 2 ], 34.0 (CCCC 2 ), 39.5 (C 2 C 2 CC 3 ), 41.3 (C 3 CCC 2 C), 45.7 (CCCC 2 ), 74.5 (C 3 C), 75.4 (C), 79.4 (CCCC 2 ), (C 3 CCC 2 C 2 ), (C 3 CCC 2 C), (C 2 C 2 CC 3 ), (C 3 CCC 2 C 2 ). MS (ESI): m/z (%) = 459/460 (100/31) [M+Na] +. IR (ATR): ν ~ = 3507 (w), 3471 (w), 2954 (m), 2929 (m), 2889 (m), 2857 (m), 1463 (w), 1387 (w), 1365 (w), 1252 (m), 1056 (s), 1046 (s), 1008 (m), 988 (w), 900 (m), 869 (m), 834 (s), 774 (s), 757 (s), 666 (w), 553 (w). UV (Me): λ ma (lg ε) = 203 (3.97). RESIMS calcd. for C SiNa [M+Na] + : , found (1S,2R,3E,7E,10R,12R)-10-Acetyl-2-[(tert-butyldimethylsilyl)oy]-12-isopropyl- 3,7-dimethylcyclododeca-3,7-dienecarboylic acid (13) TBS 13 To a solution of hydroperoide 10 (18 mg, mmol, equiv) in CCl 4 (5.5 ml) were added two drops of Cl (12 M, 50 µl) and the solution was stirred for 21 h at 40 C an 4 d at rt. The solvent was evaporated and the residue was purified by column chromatography on silica [PE/EA (5:1)] to obtain acid 13 (8 mg, mmol, 45%) as colorless solid. TLC [silica, PE/EA: (5:1)]: R f = [ α ] 23 D (c 0.33, CCl 3 ).

10 9 1 NMR (400 Mz, CDCl 3 ): δ = [s, 3, Si(C 3 )], [s, 3, Si(C 3 )], 0.81 [s, 3 J = 10.7 z, 1, C 3 CCC 2 C), (m, 1, CC 2 C 2 C). 13 C NMR (100 Mz, CDCl 3 ): δ = -5.4 [Si(C 3 )], -4.7 [Si(C 3 )], 9.5 (C 3 CCC 2 C 2 ), 14.7 (C 3 CCC 2 C), 15.6 [C(C 3 ) 2 ], 18.0 [SiC(C 3 ) 3 ], 21.2 [C(C 3 ) 2 ], 23.8 (CCCC 2 ), 24.3 (C 2 C 2 CC 3 ), 24.6 (C 3 CCC 2 C), 25.7 [3C, SiC(C 3 ) 3 ], 27.5 [C(C 3 ) 2 ], 28.8 (CC 3 ), 38.3 (CCCC 2 ), 38.8 (C 2 C 2 CC 3 ), 46.8 (C 3 CCC 2 C), 47.7 (CCCC 2 ), 80.3 (CCCC 2 ), (C 3 CCC 2 C), (C 3 CCC 2 C 2 ), (C 3 CCC 2 C 2 ), (C 2 C 2 CC 3 ), (C), (C). MS (EI, 70 ev): m/z (%) = 435 (2) [M-Me] +, 393 (42) [M-tBu] +, 301 (9), 273 (10), 255 (13), 225 (10), 198 (18), 141 (22), 133 (27), 93 (18), 75 (100), 43 (37). MS (ESI): m/z (%) = 473/474 (100/34) [M+Na] +. IR (ATR): ν ~ = 2955 (m), 2928 (m), 2899 (m), 2856 (m), 1701 (s), 1464 (w), 1441 (w), 1359 (w), 1249 (w), 1225 (w), 1208 (w), 1049 (s), 859 (m), 834 (s), 776 (s), 667 (w), 611 (w), 573 (w). UV (Me): λ ma (lg ε) = 202 (3.91). REIMS calcd. for C Si [M-tBu] + : , found M. p.: C. 9, SiC(C 3 ) 3 ], 0.85 [d, 3 J = 7.2 z, 3, C(C 3 ) 2 ], 1.07 [d, 3 J = 7.0 z, 3, C(C 3 ) 2 ], (m, 1, CCCC 2 ), 1.46 (s, 3, C 2 C 2 CC 3 ), 1.50 (s, 3, C 2 C 2 CCC 3 ), (m, 1, CCCC 2 ), [m, 1, C(C 3 ) 2 ], (m, 3, CCCC 2, C 2 C 2 CC 3, C 2 C 2 CC 3 ), (m, 2, C 2 C 2 CC 3, C 3 CCC 2 C), 2.20 (s, 3, CC 3 ), (m, 1, C 3 CCC 2 C), 2.38 (ddd, 3 J = 4.2 z, 3 J = 12.2 z, 2 J = 17.1 z, 1, C 2 C 2 CC 3 ), (m, 1, C 3 CCC 2 C), 2.81 (dd, 3 J = 2.8 z, 3 J = 10.3 z, 1, CCCC 2 ), 4.32 (d, 3 J = 10.3 z, 1, CCCC 2 ), 4.93 (d, (1S,2R,3E,7E,10R,12R)-2-[(tert-Butyldimethylsilyl)oy]-12-isopropyl-3,7- dimethyl-10-(prop-1-en-2-yl)cyclododeca-3,7-dienecarboylic acid (14) 14 TBS To a suspension of methyltriphenylphosphonium bromide (189 mg, 0.53 mmol, 10.0 equiv) in TF (3.0 ml) was added n-buli (2.5 M in heane, 0.21 ml, 0.53 mmol, 10.0 equiv) at 0 C. After stirring for 1.0 h at 0 C, 13 (24 mg, mmol, equiv) in TF (6.0 ml) was added and kept at rt for 18 h. 1 M Cl was added, the aqueous phase was etracted with Et 2 (3) and the combined organic phases were dried over MgS 4 and filtered. The residue obtained after evaporation of the solvent was purified by column chromatography on

11 10 silica [PE/EA (10:1)] to obtain dihydro-carboycubiten 14 (14 mg, mmol, 59%) as colorless solid. TLC [silica, PE/EA: (10:1)]: R f = [ α ] 26 D (c 0.23, CCl 3 ). 1 NMR (600 Mz, CDCl 3 ): δ = [s, 3, Si(C 3 )], [s, 3, Si(C 3 )], 0.80 [s, 9, SiC(C 3 ) 3 ], 0.80 [d, 3 J = 6.7 z, 3, C(C 3 ) 2 ], 1.05 [d, 3 J = 6.7 z, 3, C(C 3 ) 2 ], (m, 1, CCCC 2 ), (m, 1, CCCC 2 ), 1.48 (s, 3, C 2 C 2 CC 3 ), 1.51 (s, 3, C 2 C 2 CCC 3 ), (m, 4, C 2 =CC 3, CCCC 2 ), [m, 1, C(C 3 ) 2 ], (m, 3, C 2 C 2 CC 3, C 2 C 2 CC 3, C 3 CCC 2 C), (m, 3, C 2 C 2 CC 3, C 3 CCC 2 C, C 3 CCC 2 C), (m, 1, C 2 C 2 CC 3 ), 2.80 (dd, 3 J = 2.6 z, 3 J = 10.3 z, 1, CCCC 2 ), 4.35 (d, 3 J = 10.3 z, 1, CCCC 2 ), 4.83 (s, 1, C 2 =CC 3 ), 4.87 (s, 1, C 2 =CC 3 ), 4.92 (d, 3 J = 9.5 z, 1, C 3 CCC 2 C), (m, 1, CC 2 C 2 C). 13 C NMR (150 Mz, CDCl 3 ): δ = -5.4 [Si(C 3 )], -4.7 [Si(C 3 )], 9.5 (C 3 CCC 2 C 2 ), 15.1 (C 3 CCC 2 C), 15.5 [C(C 3 ) 2 ], 18.0 [SiC(C 3 ) 3 ], 21.3 [C(C 3 ) 2 ], 23.3 (C 2 =CC 3 ), 24.3 (C 2 C 2 CC 3 ), 25.7 [3C, SiC(C 3 ) 3 ], 26.0 (2C, C 3 CCC 2 C, CCCC 2 ), 27.4 [C(C 3 ) 2 ], 38.7 (C 3 CCC 2 C), 38.8 (CCCC 2 ), 39.0 (C 2 C 2 CC 3 ), 47.9 (CCCC 2 ), 80.6 (CCCC 2 ), (C 2 =CC 3 ), (C 3 CCC 2 C), (C 3 CCC 2 C 2 ), (C 3 CCC 2 C 2 ), (C 2 C 2 CC 3 ), (C 2 =CC 3 ), (C). MS (ESI): m/z (%) = 471/472 (100/36) [M+Na] +. IR (ATR): ν ~ = 2954 (m), 2928 (m), 2856 (m), 1701 (s), 1462 (w), 1442 (w), 1250 (w), 1227 (m), 1209 (w), 1048 (s), 887 (m), 860 (s), 835 (s), 775 (s), 666 (w), 613 (w), 577 (w), 547 (w). UV (Me): λ ma (lg ε) = 202 (4.09). RMS (microesi) calcd. for C SiNa [M+Na] + : , found M. p.: C.

12 11 (R,2E,6E)-8-[(tert-Butyldimethylsilyl)oy]-3,7-dimethyl-8-[(1S,6S)-3-methyl-2- oo-6-(prop-1-en-2-yl)cyclohe-3-en-1-yl]octa-2,6-dien-1-yl acetate (17a) 17 4 (2.09 g, 5.80 mmol, equiv) was dissolved in DMF (6.0 ml) and imidazole (869 mg, 12.8 mmol, 2.20 equiv) was added. After 10 min TBS TBSCl (1.14 g, 7.56 mmol, 1.30 equiv) was added 17a and the resulting solution was stirred for 20 h at rt. Water was added and the solution was etracted with Et 2 (3). The organic phase was dried over MgS 4, filtered and the solvent was evaporated. The residue obtained was purified by column chromatography on silica [PE/EA (12:1)] to give 17a (2.70 g, 5.68 mmol, 98%) as colorless oil. TLC [silica, PE/EA: (10:1)]: R f = [ α ] 25 D 9.27 (c 1.03, CCl 3 ). 1 NMR (400 Mz, CDCl 3 ): δ = [s, 3, Si(C 3 )], [s, 3, Si(C 3 )], 0.82 [s, 9, SiC(C 3 ) 3 ], 1.61 [s, 3, C(Si)CC 3 ], 1.68 (s, 3, C 2 CC 3 ), 1.71 (s, 3, C 2 C 2 CC 3 ), (m, 3, CCC 3 ), 2.05 (s, 3, CC 3 ), (m, 2, C 2 C 2 CC 3 ), (m, 2, C 2 C 2 CC 3 ), (m, 1, CCC 2 ), (m, 1, CCC 2 ), (m, 1, CCC 2 ), 2.66 (dd, 3 J = 1.9 z, 3 J = 9.8 z, 1, CCC 2 ), 4.26 [d, 3 J = 9.7 z, 1, C(Si)CC 3 ], 4.58 (d, 3 J = 7.0 z, 2, CC 2 ), 4.65 (s, 1, C 2 CC 3 ), 4.75 (s, 1, C 2 CC 3 ), (m, 2, CC 2 C 2, CC 2 ), (m, 1, CC 2 CC). 13 C NMR (100 Mz, CDCl 3 ): δ = -5.3 [Si(C 3 )], -4.8 [Si(C 3 )], 10.2 [C(Si)CC 3 ], 16.1 (CCC 3 ), 16.2 (C 2 C 2 CC 3 ), 18.0 [SiC(C 3 ) 3 ], 21.0 (CC 3 ), 21.9 (C 2 CC 3 ), 25.5 (C 2 C 2 CC 3 ), 25.7 [3C, SiC(C 3 ) 3 ], 26.5 (CCC 2 ), 38.9 (C 2 C 2 CC 3 ), 42.4 (CCC 2 ), 54.3 (CCC 2 ), 61.2 (CC 2 ), 79.5 [C(Si)CC 3 ], (C 2 CC 3 ), (CC 2 ), (CC 2 C 2 ), (CCC 3 ), [C(Si)CC 3 ], (CC 2 CC), (C 2 C 2 CC 3 ), (C 2 CC 3 ), (CC 3 ), (C). MS (ESI): m/z (%) = 497/498 (100/38) [M+Na] +. IR (ATR): ν ~ = 2952 (w), 2929 (w), 2890 (w), 2856 (w), 1739 (m), 1679 (m), 1442 (w), 1364 (m), 1230 (s), 1088 (m), 1063 (s), 1024 (m), 958 (w), 875 (m), 835 (s), 775 (s), 667 (w), 577 (w). UV (Me): λ ma (lg ε) = 203 (4.20), 239 (3.79), 327 (2.33). RMS (microesi) calcd. for C SiNa [M+Na] + : , found For the synthesis of 17 see: Schöttner, E.; Jones, P. G.; Lindel, T. Synthesis 2009,

13 12 (5S,6S)-6-[(R,2E,6E)-1-[(tert-Butyldimethylsilyl)oy]-8-hydroy-2,6-dimethylocta- 2,6-dien-1-yl]-2-methyl-5-(prop-1-en-2-yl)cyclohe-2-enone (17b) 17a (4.12 g, 8.67 mmol, equiv) was dissolved in TF/ 2 (1:1, 28.0 ml) and Li 2 (1.82 g, 43.3 mmol, 5.00 equiv) was added. After stirring at rt for 5 d, saturated N 4 Cl solution was added and the TBS solution was etracted with Et 2 (3). The organic 17b phase was dried over MgS 4. The residue obtained after evaporation of the solvent was purified by column chromatography on silica [PE/EA (10:1) (4:1)] to give 17b (3.38 g, 7.82 mmol, 90%) as colorless oil. TLC [silica, PE/EA: (10:1)]: R f = [ α ] 25 D 0.22 (c 1.38, CCl 3 ). 1 NMR (400 Mz, CDCl 3 ): δ = [s, 3, Si(C 3 )], [s, 3, Si(C 3 )], 0.83 [s, 9, SiC(C 3 ) 3 ], 1.62 [s, 3, C(Si)CC 3 ], 1.68 (s, 6, C 2 CC 3, C 2 C 2 CC 3 ), (m, 3, CCC 3 ), (m, 2, C 2 C 2 CC 3 ), (m, 3, CCC 2, C 2 C 2 CC 3 ), (m, 1, CCC 2 ), (m, 1, CCC 2 ), 2.66 (dd, 3 J = 1.9 z, 3 J = 9.7 z, 1, CCC 2 ), 4.15 (d, 3 J = 6.8 z, 2, CC 2 ), 4.25 [d, 3 J = 9.7 z, 1, C(Si)CC 3 ], 4.65 (s, 1, C 2 CC 3 ), 4.75 (s, 1, C 2 CC 3 ), (m, 2, CC 2, CC 2 C 2 ), (m, 1, CC 2 CC). 13 C NMR (100 Mz, CDCl 3 ): δ = -5.3 [Si(C 3 )], -4.7 [Si(C 3 )], 10.2 [C(Si)CC 3 ], 16.0 (C 2 C 2 CC 3 ), 16.1 (CCC 3 ), 18.0 [SiC(C 3 ) 3 ], 21.9 (C 2 CC 3 ), 25.6 (C 2 C 2 CC 3 ), 25.7 [3C, SiC(C 3 ) 3 ], 26.5 (CCC 2 ), 38.9 (C 2 C 2 CC 3 ), 42.4 (CCC 2 ), 54.3 (CCC 2 ), 59.3 (CC 2 ), 79.5 [C(Si)CC 3 ], (C 2 CC 3 ), (CC 2 ), (CC 2 C 2 ), (CCC 3 ), [C(Si)CC 3 ], (C 2 C 2 CC 3 ), (CC 2 CC), (C 2 CC 3 ), (C). MS (ESI): m/z (%) = 455/456 (100/31) [M+Na] +. IR (ATR): ν ~ = 3435 (br), 2952 (w), 2927 (w), 2888 (w), 2856 (w), 1671 (m), 1440 (w), 1364 (w), 1251 (m), 1087 (m), 1062 (s), 1006 (m), 875 (s), 834 (s), 774 (s), 667 (w), 577 (m). UV (Me): λ ma (lg ε) = 203 (4.16), 239 (3.76), 327 (2.04). RMS (microesi) calcd. for C SiNa [M+Na] + : , found

14 13 (R,2E,6E)-8-[(tert-Butyldimethylsilyl)oy]-3,7-dimethyl-8-[(1S,6S)-3-methyl-2- oo-6-(prop-1-en-2-yl)cyclohe-3-en-1-yl]octa-2,6-dien-1-yl diethyl phosphate (18) Alcohol 17b (3.23 g, 7.46 mmol, equiv) was dissolved under argon in dry DCM P (16.0 ml) and pyridine (0.7 ml, 8.95 mmol, TBS 1.20 equiv) and diethyl chlorophosphate 18 (1.3 ml, 8.95 mmol, 1.20 equiv) were added at 0 C. After stirring the solution for 1.5 h at 0 C 2 M Cl was added and the solution was etracted with Et 2 (3). The organic phase was washed with 2 M Cl, water and brine, dried over MgS 4, filtered and the solvent was evaporated. The phosphate 18 (4.03 g, 7.08 mmol, 95%) was obtained as a colorless oil and was used without further purification. TLC [silica, PE/EA: (1:1)]: R f = [ α ] 25 D 2.54 (c 1.26, CCl 3 ). 1 NMR (400 Mz, CDCl 3 ): δ = [s, 3, Si(C 3 )], [s, 3, Si(C 3 )], 0.82 [s, 9, SiC(C 3 ) 3 ], 1.34 (dt, 3 J = 7.1 z, 4 J = 0.9 z, 6, PC 2 C 3 ), 1.61 [s, 3, C(Si)CC 3 ], 1.68 (s, 3, C 2 CC 3 ), 1.72 (s, 3, C 2 C 2 CC 3 ), (m, 3, CCC 3 ), (m, 2, C 2 C 2 CC 3 ), (m, 3, CCC 2, C 2 C 2 CC 3 ), (m, 1, CCC 2 ), (m, 1, CCC 2 ), 2.66 (dd, 3 J = 1.8 z, 3 J = 9.8 z, 1, CCC 2 ), 4.11 (dq, 3 J = 7.1 z, 3 J = 14.2 z, 4, PC 2 C 3 ), 4.25 [d, 3 J = 9.7 z, 1, C(Si)CC 3 ], 4.56 (dd, 3 J = 7.5 z, 3 J = 7.5 z, 2, CC 2 P), 4.65 (s, 1, C 2 CC 3 ), 4.75 (s, 1, C 2 CC 3 ), (m, 2, CC 2 C 2, CC 2 P), (m, 1, CC 2 CC). 13 C NMR (100 Mz, CDCl 3 ): δ = -5.3 [Si(C 3 )], -4.8, [Si(C 3 )], 10.2 [C(Si)CC 3 ], 16.1 (d, 3 J = 6.7 z, 2C, PC 2 C 3 ), 16.2 (CCC 3 ), 16.2 (C 2 C 2 CC 3 ), 18.0 [SiC(C 3 ) 3 ], 21.9 (C 2 CC 3 ), 25.5 (C 2 C 2 CC 3 ), 25.7 [3C, SiC(C 3 ) 3 ], 26.5 (CCC 2 ), 38.9 (C 2 C 2 CC 3 ), 42.4 (CCC 2 ), 54.3 (CCC 2 ), 63.6 (d, 2 J = 5.8 z, 2C, PC 2 C 3 ), 63.9 (d, 2 J = 5.6 z, CC 2 P), 79.5 [C(Si)CC 3 ], (C 2 CC 3 ), (d, 3 J = 6.9 z, CC 2 P), (CC 2 C 2 ), (CCC 3 ), [C(Si)CC 3 ], (CC 2 CC), (C 2 C 2 CC 3 ), (C 2 CC 3 ), (C). MS (ESI): m/z (%) = 591/592 (100/36). IR (ATR): ν ~ = 2952 (w), 2929 (m), 2856 (w), 1678 (m), 1444 (w), 1365 (w), 1454 (m), 1166 (w), 1088 (m), 1063 (m), 1029 (s), 1005 (s), 979 (s), 875 (m), 835 (s), 775 (s), 667 (w). UV (Me): λ ma (lg ε) = 203 (4.26), 227 (3.96).

15 14 RMS (microesi) calcd. for C SiPNa [M+Na] + : , found (1S,3E,7E,9R,10S,12S,14S)-9-[(tert-Butyldimethylsilyl)oy]-4,8,12-trimethyl-14- (prop-1-en-2-yl)bicyclo[8.2.2]tetradeca-3,7-dien-11-one (19) Samarium (1.79 g, 11.9 mmol, 5.50 equiv) was stirred under argon in dry degased TF (108 ml) and diiodoethane (3.04 g, TBS 10.8 mmol, 5.00 equiv) was added. After 3 h the miture was cooled to 5-10 C and 18 (1.23 g, 2.16 mmol, equiv), dissolved in TF (252 ml) was dropped to the blue SmI 2 19 solution over 1.5 h and the miture was stirred for 1.5 h at rt. The reaction was quenched with 1 M Cl and was etracted with Et 2 (4). The organic phase was washed with saturated Na 2 S 2 3, water and brine and dried over MgS 4. After evaporation the residue was purified by column chromatography on silica [PE/DCM (6:1)] to give the bicycle 19 (507 mg, 1.22 mmol, 56%) as a colorless oil. TLC [silica, PE/EA: (20:1)]: R f = [ α ] 25 D +234 (c 1.17, CCl 3 ). 1 NMR (400 Mz, CDCl 3 ): δ = 0.02 [s, 3, Si(C 3 )], 0.04 [s, 3, Si(C 3 )], 0.88 [s, 9, SiC(C 3 ) 3 ], 1.06 (d, 3 J = 6.7 z, 3, CCC 3 ), 1.54 (s, 3, C 2 C 2 CC 3 ), (m, 1, CCCC 2 ), 1.60 (s, 3, C 2 C 2 CCC 3 ), 1.83 (s, 3, C 2 CC 3 ), (m, 6, C 2 C 2 CC 3, C 2 C 2 CC 3, C 3 CCC 2 C, CCCC 2 ), (m, 1, C 2 C 2 CC 3 ), (m, 1, C 3 CCC 2 C), 2.64 (brs, 1, CCCC 2 ), (m, 1, CCC 3 ), 2.90 (m, 1, CCCC 2 ), (m, 1, C 3 CCC 2 C), (m, 1, C 2 CC 3 ), 4.93 (m, 1, C 2 CC 3 ), (m, 1, CC 2 C 2 C), 5.25 (d, 3 J = 3.3 z, 1, CCCC 2 ). 13 C NMR (100 Mz, CDCl 3 ): δ = -5.1 [Si(C 3 )], -5.1 [Si(C 3 )], 10.9 (CCC 3 ), 12.8 (C 3 CCC 2 C 2 ), 15.4 (C 2 C 2 CC 3 ), 18.2 [SiC(C 3 ) 3 ], 22.2 (C 2 CC 3 ), 25.2 (C 2 C 2 CC 3 ), 25.9 [3C, SiC(C 3 ) 3 ], 29.1 (C 3 CCC 2 C), 29.2 (CCCC 2 ), 37.3 (C 3 CCC 2 C), 39.4 (CCCC 2 ), 39.9 (C 2 C 2 CC 3 ), 43.9 (C 3 CC), 60.0 (CCCC 2 ), 73.9 (CCCC 2 ), (C 2 CC 3 ), (C 3 CCC 2 C), (C 3 CCC 2 C 2 ), (C 3 CCC 2 C 2 ), (C 2 C 2 CC 3 ), (C 2 CC 3 ), (C). MS (EI, 70 ev): m/z (%) = 416 (4) [M + ], 359 (8), 269 (2), 198 (100), 141 (96), 73 (23). IR (ATR): ν ~ = 2954 (m), 2928 (m), 2856 (m), 1705 (m), 1442 (w), 1375 (w), 1252 (m), 1079 (m), 1056 (s), 1036 (s), 896 (s), 834 (s), 813 (m), 774 (s), 671 (w), 589 (w), 558 (w).

16 15 UV (Me): λ ma (lg ε) = 203 (4.03). REIMS calcd. for C Si [M + ]: , found (1R,2R,3E,7E,10S,11R,12R,13S)-2-[(tert-Butyldimethylsilyl)oy]-3,7,11-trimethyl- 13-(prop-1-en-2-yl)bicyclo[8.2.2]tetradeca-3,7-diene-11,12-diol (20) 20 TBS 19 (48 mg, 0.12 mmol, equiv) was dissolved in TF (10.0 ml) and was cooled to -25 C. LiAl 4 (4 M in Et 2, 0.15 ml, 0.6 mmol, 5.00 equiv) was added and the solution was warmed to -20 C and stirred for 3 h at this temperature. Water was added and the aqueous phase was etracted with Et 2 (3). The combined organic phases were washed with brine, dried over MgS 4, filtered and evaporated. The residue was purified by column chromatography on silica [PE/DCM (5:1)] to give diol 20 (35 mg, 0.81 mmol, 68%) as colorless oil. TLC [silica, PE/EA: (5:1)]: R f = [ α ] 22 D +0.5 (c 2.42, CCl 3 ). 1 NMR (600 Mz, CDCl 3 ): δ = [s, 3, Si(C 3 )], 0.02 [s, 3, Si(C 3 )], 0.85 [s, 9, SiC(C 3 ) 3 ], 1.38 (s, 3, C 3 C), (m, 4, C 2 C 2 CC 3, C 3 C), 1.64 (ddd, 3 J = 3.2 z, 3 J = 6.4 z, 2 J = 14.2 z, 1, CCCC 2 ), 1.74 (s, 3, C 2 C 2 CCC 3 ), 1.79 (s, 3, C 2 CC 3 ), (m, 1, C 3 CCC 2 C), 2.02 (ddd, 3 J = 6.4 z, 3 J = 11.0 z, 2 J = 14.2 z, 1, CCCC 2 ), (m, 1, C 3 CCC 2 C), 2.33 (d, 3 J = 11.6 z, 1, C), (m, 4, C 2 C 2 CC 3, C 2 C 2 CC 3 ), 2.44 (dd, 3 J = 10.9 z, 2 J = 14.7 z, 1, C 3 CCC 2 C), 2.56 (m, 1, CCCC 2 ), (m, 1, CCCC 2 ), 3.50 (dd, 3 J = 6.6 z, 3 J = 11.6 z, 1, C), 4.58 s, 1, CCCC 2 ), 4.73 (s, 1, C 2 CC 3 ), 4.79 (s, 1, C 2 CC 3 ), 5.52 (dd, 3 J = 5.5 z, 3 J = 10.5 z, 1, C 3 CCC 2 C), 5.60 (t, 3 J = 6.8 z, 1, CC 2 C 2 C). 13 C NMR (150 Mz, CDCl 3 ): δ = -5.0 [Si(C 3 )], -4.9 [Si(C 3 )], 15.2 (C 3 CCC 2 C), 16.6 (C 3 CCC 2 C 2 ), 18.2 [SiC(C 3 ) 3 ], 20.0 (C 2 CC 3 ), 25.2 (C 2 C 2 CC 3 ), 25.8 [3C, SiC(C 3 ) 3 ], 26.4 (C 3 C), 28.5 (C 3 CCC 2 C), 30.3 (CCCC 2 ), 36.7 (CCCC 2 ), 40.5 (C 2 C 2 CC 3 ), 41.6 (C 3 CCC 2 C), 44.7 (CCCC 2 ), 74.4 (C 3 C), 74.5 (C), 78.6 (CCCC 2 ), (C 2 CC 3 ), (C 3 CCC 2 C 2 ), (C 3 CCC 2 C), (C 2 C 2 CC 3 ), (C 3 CCC 2 C 2 ), (C 2 CC 3 ). MS (microesi): m/z (%) = 457/458 (100/32) [M+Na] +. IR (ATR): ν ~ = 3515 (w), 3471 (w), 2953 (m), 2927 (m), 2856 (m), 1726 (w), 1639 (w),

17 (m), 1364 (m), 1251 (m), 1082 (s), 1048 (s), 1007 (w), 934 (w), 905 (w), 864 (s), 835 (s), 774 (s), 667 (w). UV (Me): λ ma (lg ε) = 204 (3.87). RMS (microesi) calcd. for C SiNa [M+Na] + : , found (1S,2R,3E,7E,10S,12S)-10-Acetyl-2-[(tert-butyldimethylsilyl)oy]-3,7-dimethyl- 12-(prop-1-en-2-yl)cyclododeca-3,7-dienecarboylic acid (22) 22 TBS To a solution of diol 20 (68 mg, mmol, equiv) in Et (10.0 ml) was added 5 I 6 (39 mg, 0.17 mmol, 1.10 equiv) and the miture was stirred at rt for 20 h. Water was added and the aqueous phase was etracted with Et 2 (3). The combined organic layers were dried over MgS 4, filtered and evaporated. The crude product was dissolved in tert-bu (8.0 ml) and 2-methylbut-2-ene (85%, 1.5 ml, 14.2 mmol, 91.0 equiv) was added. To this solution NaCl 2 (128 mg, 1.41 mmol, 9.00 equiv) and Na 2 P 4 (188 mg; 1.57 mmol, 10.0 equiv) in water (2.0 ml) was dropped slowly and stirred for 16 h at rt. After addition of a phosphate buffer solution (p 7) the aqueous phase was etracted with DCM (3) and the combined organic phases were washed with brine. After drying over MgS 4 and filtration, the solvent was evaporated. The residue was purified by column chromatography [PE/EA (5:1)] and acid 22 (21 mg, mmol, 30%) was obtained as colorless solid. TLC [silica, PE/EA: (5:1)]: R f = [ α ] 22 D (c 0.24, CCl 3 ). 1 NMR (600 Mz, CDCl 3 ): δ = [s, 3, Si(C 3 )], 0.02 [s, 3, Si(C 3 )], 0.81 [s, 9, SiC(C 3 ) 3 ], 1.50 (s, 3, C 2 C 2 CC 3 ), 1.56 (s, 3, C 2 C 2 CCC 3 ), (m, 1, CCCC 2 ), 1.77 (s, 3, C 2 CC 3 ), (m, 1, CCCC 2 ), (m, 3, C 2 C 2 CC 3, CCCC 2, C 2 C 2 CC 3 ), (m, 1, C 3 CCC 2 C), 2.17 (s, 3, CC 3 ), (m, 2, C 3 CCC 2 C, C 2 C 2 CC 3 ), (m, 1, C 2 C 2 CC 3 ), (m, 1, C 3 CCC 2 C), 2.76 (dd, 3 J = 3.2 z, 3 J = 10.4 z, 1, CCCC 2 ), 4.37 (d, 3 J = 10.4 z, 1, CCCC 2 ), 4.68 (s, 1, C 2 CC 3 ), 4.84 (d, 3 J = 10.6 z, 1, C 3 CCC 2 C), 4.94 (s, 1, C 2 CC 3 ), (m, 1, CC 2 C 2 C). 13 C NMR (150 Mz, CDCl 3 ): δ = -5.4 [Si(C 3 )], -4.7 [Si(C 3 )], 9.5 (C 3 CCC 2 C 2 ), 14.8 (C 3 CCC 2 C), 18.0 [SiC(C 3 ) 3 ], 21.9 (C 2 CC 3 ), 23.2 (CCCC 2 ), 24.4 (C 2 C 2 CC 3 ), 24.7 (C 3 CCC 2 C), 25.7 [3C, SiC(C 3 ) 3 ], 28.7 (CC 3 ), 38.8 (C 2 C 2 CC 3 ), 41.2 (CCCC 2 ), 47.3 (C 3 CCC 2 C), 53.7

18 17 (CCCC 2 ), 79.2 (CCCC 2 ), (C 2 CC 3 ), (C 3 CCC 2 C), (C 3 CCC 2 C 2 ), (C 3 CCC 2 C 2 ), (C 2 C 2 CC 3 ), (C 2 CC 3 ), (C), (C). MS (microesi): m/z (%) = 471/472 (100/31) [M+Na] +. IR (ATR): ν ~ = 2954 (m), 2928 (m), 2925 (m), 2855 (m), 1704 (s), 1443 (w), 1379 (w), 1360 (w), 1293 (w), 1252 (w), 1214 (w), 1051 (s), 1006 (w), 896 (m), 835 (s), 777 (s), 667 (w), 612 (w), 550 (w). UV (Me): λ ma (lg ε) = 203 (3.94). RMS (microesi) calcd. for C SiNa [M+Na] + : , found M. p.: C. (1S,2R,3E,7E,10S,12S)-2-[(tert-Butyldimethylsilyl)oy]-3,7-dimethyl-10,12- di(prop-1-en-2-yl)cyclododeca-3,7-dienecarboylic acid (23) 23 TBS To a suspension of methyltriphenylphosphonium bromide (164 mg, 0.46 mmol, 10.0 equiv) in TF (3.0 ml) was added n-buli (1.6 M in ean, 0.29 ml, 0.46 mmol, 10.0 equiv) at 0 C. After stirring for 1.0 h at 0 C 22 (21 mg, mmol, equiv) in TF (6.0 ml) was added and kept at rt for 16 h. 1 M Cl was added, the aqueous phase was etracted with Et 2 (3) and the combined organic phases were dried over MgS 4 and filtered. The residue obtained after evaporation of the solvent was purified by column chromatography on silica [PE/EA (20:1)] to obtain carboycubiten 23 (12 mg, mmol, 58%) as colorless solid. TLC [silica, PE/EA: (5:1)]: R f = [ α ] 21 D (c 0.73, CCl 3 ). 1 NMR (600 Mz, CDCl 3 ): δ = [s, 3, Si(C 3 )], [s, 3, Si(C 3 )], 0.80 [s, 9, SiC(C 3 ) 3 ], (m, 1, CCCC 2 ), 1.52 (s, 3, C 2 C 2 CC 3 ), 1.56 (s, 3, C 2 C 2 CCC 3 ), 1.74 (s, 3, CCCCCCC 3 ), 1.75 /s, 3, C 2 C 2 CCC 2 CCC 3 ), (m, 1, CCCC 2 ), 1.89 (td, 3 J = 3.0 z, 3 J = 12.9 z, 1, CCCC 2 ), (m, 4, C 2 C 2 CC 3, C 2 C 2 CC 3, C 2 C 2 CCC 2 ), (m, 1, CCCC 2 C), (m, 1, C 2 C 2 CC 3 ), (m, 1, C 2 C 2 CC 3 ), 2.72 (dd, 3 J = 3.1 z, 3 J = 10.4 z, 1, CCCC 2 ), 4.38 (d, 3 J = 10.4 z, 1, CCCC 2 ), 4.67 (s, 1, CCCCC 2 ), 4.80 (s, 1, C 2 C 2 CCC 2 CCC 2 ), 4.84 (s, 1, C 2 C 2 CCC 2 CCC 2 ), (m, 2, C 2 C 2 CC, CCCCC 2 ), 5.14 (dd, 3 J = 1.4 z, 3 J = 11.7 z, 1, CC 2 C 2 C).

19 18 13 C NMR (150 Mz, CDCl 3 ): δ = -5.5 [Si(C 3 )], -4.6 [Si(C 3 )], 9.6 (C 3 CCC 2 C 2 ), 15.1 (C 2 C 2 CC 3 ), 18.0 [SiC(C 3 ) 3 ], 21.5 (CCCCCCC 3 ), 23.1 (C 2 C 2 CCC 2 CCC 3 ), 24.4 (C 2 C 2 CC 3 ), 25.7 [3C, SiC(C 3 ) 3 ], 25.9 (CCCC 2 ), 26.2 (C 2 C 2 CCC 2 ), 39.0 (C 2 C 2 CC 3 ), 39.2 (CCCC 2 C), 42.0 (CCCC 2 ), 54.5 (CCCC 2 ), 79.5 (CCCC 2 ), (C 2 C 2 CCC 2 CCC 2 ), (CCCCC 2 ), (C 2 C 2 CC), (C 3 CCC 2 C 2 ), (C 3 CCC 2 C 2 ), (C 2 C 2 CC 3 ), (CCCCC 2 ), (C 2 C 2 CCC 2 CCC 2 ), (C). MS (microesi): m/z (%) = 469/470 (100/25) [M+Na] +. IR (ATR): ν ~ = 2955 (m), 2926 (m), 2855 (m), 1703 (s), 1442 (w), 1250 (w), 1215 (w), 1050 (s), 1005 (w), 889 (m), 861 (s), 835 (s), 801 (w), 775 (s), 667 (w), 614 (w). UV (Me): λ ma (lg ε) = 202 (4.00). RMS (microesi) calcd. for C SiNa [M+Na] + : , found M. p.: C.

20 3. 1 and 13 C NMR spectra 19 1 NMR (300 Mz, CDCl 3 ) CCl ppm C NMR (75 Mz, CDCl 3 ) CDCl ppm

21 1 NMR (400 Mz, CDCl 3 ) 20 CCl ppm C NMR (100 Mz, CDCl 3 ) TBS 5c CDCl ppm

22 1 NMR (400 Mz, CDCl 3 ) 21 cycloheane CCl ppm C NMR (100 Mz, CDCl 3 ) CDCl ppm

23 1 NMR (600 Mz, CDCl 3 ) 22 CCl ppm C NMR (150 Mz, CDCl 3 ) CDCl 3 cycloheane ppm

24 1 NMR (400 Mz, CDCl 3 ) 23 TBS 10 2 cycloheane CCl ppm C NMR (100 Mz, CDCl 3 ) CDCl 3 cycloheane ppm

25 1 NMR (600 Mz, CDCl 3 ) 24 TBS 10a 2 CCl ppm C NMR (150 Mz, CDCl 3 ) TBS 10a CDCl ppm

26 1 NMR (400 Mz, CDCl 3 ) 25 2 cycloheane CCl ppm C NMR (100 Mz, CDCl 3 ) CDCl ppm

27 26 1 NMR (600 Mz, CDCl 3 ) CCl ppm C NMR (150 Mz, CDCl 3 ) TBS 13 CDCl ppm

28 27 1 NMR (600 Mz, CDCl 3 ) CCl ppm C NMR (150 Mz, CDCl 3 ) CDCl ppm

29 1 NMR (400 Mz, CDCl 3 ) 28 CCl ppm C NMR (100 Mz, CDCl 3 ) CDCl ppm

30 1 NMR (400 Mz, CDCl 3 ) 29 CCl ppm C NMR (100 Mz, CDCl 3 ) CDCl ppm

31 EtAc 1 NMR (400 Mz, CDCl 3 ) 30 EtAc CCl ppm C NMR (100 Mz, CDCl 3 ) CDCl ppm

32 1 NMR (400 Mz, CDCl 3 ) 31 CCl ppm C NMR (100 Mz, CDCl 3 ) CDCl ppm

33 1 NMR (600 Mz, CDCl 3 ) 32 CCl 3 grease ppm C NMR (150 Mz, CDCl 3 ) CDCl 3 grease ppm

34 1 NMR (600 Mz, CDCl 3 ) 33 CCl 3 grease ppm C NMR (150 Mz, CDCl 3 ) CDCl 3 grease ppm

35 1 NMR (600 Mz, CDCl 3 ) 34 CCl 3 grease ppm C NMR (150 Mz, CDCl 3 ) 23 TBS CDCl 3 grease ppm

36 3. NESY correlations of diol 20 35