B. Heasley, Chem. Eur. J, vol.18, pp.3092-3120, 2012.

M. Michalak, K. Michalak, and J. Wicha, Nat. Prod. Rep, vol.34, pp.361-410, 2017.

H. Gao, R. Popescu, B. Kopp, and Z. Wang, Nat. Prod. Rep, vol.28, pp.953-969, 2011.

A. Kamboj, A. Rathour, and M. Kaur, Int. J. Pharm. Pharm. Sci, vol.5, pp.20-27, 2013.

P. Geoffroy, B. Ressault, E. Marchioni, and M. Miesch, Steroids, vol.76, pp.702-708, 2011.

P. Geoffroy, B. Ressault, E. Marchioni, M. Miesch-;-g.-d'adamino, A. Sgambato et al., Steroids, vol.76, pp.1166-1175, 2011.

P. Cipolla, F. Fusi, ;. Cardona, and . Asano, Modern Alkaloids : Structure, Isolation, Synthesis and Biology, vol.13, pp.111-138, 2008.

Q. Luo, L. Tian, Y. Di, X. Yan, X. Wei et al., Org. Lett, vol.17, pp.1565-1568, 2015.

T. R. Hoye, J. T. North, L. J. Yao, ;. Oka, K. Sato et al., Br. J. Pharmacol, vol.59, pp.1959-1966, 1994.

R. Boehringer, P. Geoffroy, and M. Miesch, Org. Biomol. Chem, vol.13, pp.6940-6943, 2015.

J. C. Green and T. R. Pettus, J. Am. Chem. Soc, vol.133, pp.1603-1608, 2011.

, Revue concernant la chimie des cédrènes de, The Way Of Synthesis, 1955.

-. Wiley and . Vch, , pp.229-254, 2007.

, De plus, au départ de chaque énantiomère du diène (+)-196, notre réaction de Diels-Alder est diastéréospécifique et nous a permis d'isoler les différents adduits avec de très bons rendements de 37 et 39 %. En effet, dans ce cas particulier, le rendement maximum pour chaque adduit ne pouvait pas dépasser 50 %. b) Utilisation de la (S)-carvone et synthèse d'un ent-14?-hydroxytéroide énantiopur Toutes choses égales par ailleurs, la (S)-carvone 245, également commercialement disponible, devrait conduire aux énantiomères des adduits obtenus avec la (R)-carvone 238. Pour le vérifier, notre réaction de Diels-Alder a été réalisée dans les mêmes conditions avec la (S)-carvone 245 comme diénophile. Effectivement, nous avons obtenu les énantiomères des adduits précédents avec des rendements identiques, de manière diastéréo et énantiospécifique et avec un excès énantiomérique supérieur à 98 %. De plus, la structure de l'adduit-exo (+)239 102 , confirmée par diffraction des rayons X, représentait bien l'énantiomère d'un 14?hydroxyandrostane naturel. Il s'agissait donc d'un ent-14?-hydroxystéroïde. Ces derniers n'étant pas naturels, En présence de (R)-carvone 238 comme diénophile et du diène racémique (+)-196, nous avons synthétisé les adduits optiquement purs (-)-239 et (-)-240

, Schéma 79 : réaction de Diels-Alder entre le diène (+)-196 et la (S)-carvone 245

, nous avons montré qu'avec la (R)-carvone 238 ou la (S)-carvone 245, les deux énantiomères du diène (+)-196ont été convertis en deux produits distincts énantiopurs avec des rendements identiques. Dans chaque cas, les adduits obtenus n'étaient pas des isomères l'un de l'autre. Ainsi, nous pouvons affirmer que notre réaction de Diels-Alder répond aux critères requis pour confirmer le fait qu'elle se déroule sous le contrôle d'une résolution cinétique parallèle chemodivergente, vol.103, p.104

P. J. Walsh and M. C. Kozlowski, Fundamentals of Asymetric Catalysis. University Science Books, 2008.

J. R. Dehli and V. Gotor, Chem. Soc. Rev, vol.31, pp.365-370, 2002.

, 101 112. L'élongation de la chaîne nous a donné accès à l'oléfine activée (+)-268. Cependant, les deux méthodes de cyclisation développées au laboratoire, à savoir, les réactions de MBH et de HMA, ne nous avaient pas permis d'isoler l'hydrindane polyfonctionnalisé (+)-269 à pression atmosphérique, vol.85

, synthèse du précurseur (+)-268 de l'hydrindane polyfonctionnalisé, vol.85, p.269

. Cependant, lorsque notre réaction de MBH a été réalisée sous haute pression (9 kbar), nous avons isolé l'hydrindane polyfonctionnalisé (+)-269 avec un rendement de 65 % de manière diastéréospécifique

, synthèse racémique du diène, vol.86, p.270

, Au départ de la 2-méthyl-cyclopentane-1,3-dione 6, de la méthylvinylcétone 15 et sous une catalyse acide, la tricétone 271 a été synthétisée. Puis, en présence d'un catalyseur chiral, à savoir, la (L)-proline 272, nous avons obtenu l'hydrindane (+)-273. En traitant in-situ le milieu réactionnel par une solution de H2SO4, une dernière étape de déshydration a conduit à la (+)-cétone de Hajos-Parish (+)-101 présentant un excès énantiomérique supérieur à 98 %, Ayant optimisé la voie d'accès au diène polyfonctionnalisé (+)-270, nous avons réalisé la synthèse de ce dernier en voie asymétrique, vol.113

, en 9 étapes et avec un rendement global de 16 % au départ de la (+)-cétone de Hajos-Parrish (+)-101. Comme aucune étape d'isomérisation n'a été mise en jeu, il était raisonnable de penser que le diène (+)-270 présentait le même excès énantiomérique, vol.87

Z. G. Hajos, D. R. Parrish, and E. P. Oliveto, Tetrahedron, vol.24, pp.2039-2046, 1967.

Z. G. Hajos and D. R. Parrisch, Org. Synth, vol.63, p.26, 1985.

S. Bahmanyar and K. N. Houk, J. Am. Chem. Soc, vol.123, p.11273, 2001.

B. Bradshaw and J. Bonjoch, , vol.23, pp.337-356, 2012.

Y. Tang, J. Liu, P. Chen, M. Lv, Z. Wang et al., J. Org. Chem, vol.79, pp.11729-11734, 2014.

, Schéma, vol.87

, Au départ de cette dernière, une réduction diastéréospécifique effectuée à l'aide de NaBH4, suivie de l'introduction d'un groupement tosylate et d'une substitution nucléophile par du NaCN a donné accès au composé (+)-274. Puis en 4 étapes, nous avons obtenu l'alcool primaire (+)-275 avec un très bon rendement de 78 %. 117 Une protection de ce dernier a donné le composé (+)-276. La coupure oxydante de l'alcène, la réduction de l'acide obtenu et l'oxydation de ce dernier a permis l'accès à l'aldéhyde (+)-277. Une élongation de la chaîne par une réaction de Wittig a conduit au composé (+)-278. La réaction de MBH a à nouveau été réalisée sous haute-pression (9 kbar) et a permis la synthèse diastéréospécifique de l'hydrindane polyfonctionnalisé (+)-279, 280, possédant une chaîne fonctionnalisée en position 17, a également été préparé en voie racémique, vol.88

, synthèse du diène racémique, vol.88, p.280

. Enfin, il est tout à fait raisonnable de dire que le diène énantiopur (+)-280 pourrait également être obtenu au départ (+)-cétone de Hajos-Parish (+)-101 en utilisant la route synthétique décrite précédemment. Toutefois, par un manque de temps, nous n'avons pas réalisé cette synthèse asymétrique, vol.89

J. C. Green and T. R. Pettus, J. Am. Chem. Soc, vol.133, pp.1603-1608, 2011.

, Revue concernant la chimie des cédrènes de, The Way Of Synthesis, 1955.

-. Wiley and . Vch, , pp.229-254, 2007.

M. Kousara, F. L. Bideau, R. Ibrahim, A. Ferry, P. Venot et al., Synthesis, vol.48, pp.1637-1646, 2016.

F. L. Bideau, M. Kousara, L. Chen, L. Wei, and F. Dumas, Chem. Rev, vol.117, pp.6110-6159, 2017.

M. Presset, Y. Coquerel, and J. Rodriguez, Eur. J. Org. Chem, pp.2247-2260, 2010.

C. Suivant-une-stratégie-similaire, Iwata et coll. avaient réalisé la synthèse formelle de la (+)-quadrone 20, 202 Le système bicyclique ponté 580 a été synthétisé au départ de la, vol.201, p.4

S. D. Burke, C. W. Murtiashaw, J. O. Saunders, and M. S. Dike, J. Am. Chem. Soc, vol.104, pp.872-874, 1982.

S. D. Burke, C. W. Murtiashaw, and J. A. Oplinger, Tetrahedron Lett, vol.24, pp.2949-2952, 1983.

S. D. Burke, C. W. Murtiashaw, J. O. Saunders, J. A. Oplinger, and M. S. Dike, J. Am. Chem. Soc, vol.106, pp.4558-4566, 1984.

K. Takeda, Y. Shimono, and E. Yoshii, J. Am. Chem. Soc, vol.105, pp.563-568, 1983.

T. Imanishi, M. Matsui, M. Yamashita, ,. , and C. Iwata, Tetrahedron Lett, vol.27, pp.3161-3164, 1986.

T. Imanishi, M. Matsui, M. Yamashita, ,. , and C. Iwata, J. Chem. Soc., Chem. Commun, pp.1802-1804, 1987.

, Compound (+)-518

, 516 (0.230 g, 0.47 mmol) and p-methoxyphenyl vinyl ketone (0.157 g, 1.19 mmol) in CH2Cl2 (5 mL) was added Grubbs second-generation catalyst (12 mg

, mmol) at room temperature. Then, the mixture was stirred at 40 °C for 3h. After concentration under reduced pressure, the crude product was purified by column chromatography on silica gel

H. Nmr, SiC(CH3)2(CH3)3)); 2.52 (m, 2H, NCH2CH2); 3.28 (m, 1H, NCH2CH2); 3.54 (m, 1H, NCH2CH2); 3.83 (dd, J = 5.1 Hz, 3.1 Hz, 1H, CHOBn), vol.9

C. Nmr, SiC(CH3)2(CH3)3)); 25.6 (3 CH, SiC(CH3)2(CH3)3)3); 31.1 (CH2, NCH2CH2), MHz, vol.17, issue.125

, =CH), =CH, vol.128, issue.2

, iR (ATR): ? (CO) = 1706, 1672 cm-1 , ? (OTBS) = 1069, 856 cm-1 , ? (Ar) =, pp.736-737

, HRMS (ESI) m/z: C35H43NO5Si [M + Na] + calc. 608.2809, found, vol.608, p.2803

, D : +34.2 (c = 0.5, CHCl3)

, 516 (0.230 g, 0.47 mmol) and p-methoxyphenyl vinyl ketone (0.193 g, 1.19 mmol) in CH2Cl2 (5 mL) was added Grubbs second-generation catalyst (12 mg

, mmol) at room temperature. Then, the mixture was stirred at 40 °C for 3h. After concentration under reduced pressure, the crude product was purified by column chromatography on silica gel (petroleum ether/AcOEt 70/30), vol.76

H. Nmr, SiCH3); 0.12 (s, 3H, SiCH3); 0.88 (s, 9H, SiC(CH3)2(CH3)3)); 2.55 (m, 2H, NCH2CH2); 3.30 (m, 1H, NCH2CH2), MHz, issue.500, p.3

1. Hz and C. ,

C. Nmr, SiC(CH3)2(CH3)3)); 25.6 (3 CH3, SiC(CH3)2(CH3)3), MHz, vol.17, issue.125

, =CH); 130.5 (=C), =CH, vol.128, issue.1

, 4 (=C); 143.6 (CH), vol.137

, iR (ATR): ? (CO) = 1706, 1598 cm-1 , ? (OTBS) = 1070, 856 cm-1 , ? (Ar) =, pp.736-737

, HRMS (ESI) m/z: C36H45NO6Si [M + Na

, 33 mmol) carefully. After stirring for 1 h at room temperature, allylbromine (2.90 mL, 33.3 mmol) was added to the reaction mixture which was then stirred at 50 °C for 20 h. After, water (100 mL) was slowly added to the residue, and the mixture was extracted with AcOEt (4x 100 mL). The combined organic layers were washed with sat. NaCl (5x 100 mL), were dried over Na2SO4, filtered and concentrated under reduced pressure. The crude material was purified by silica gel chromatography, DMF (50 mL), was added sodium hydride (0.87 g, vol.36

H. Nmr, MHz, issue.500

C. Nmr, CDCl3): 28.2 (2CH2, (O)CCH2CH2C(O), MHz, vol.40, issue.125

, 33 mmol) was added in small portions to a solution of alkene 523 (2.8 g, 16.75 mmol) in methanol (100 mL) at 0 °C. The reaction mixture was stirred 3 h at 0 °C and was allowed to warm to room temperature. The mixture was diluted with water (100 mL) and aqueous saturated NaHCO3 (100 mL), then CH2Cl2 (150 mL) was added and the layers were extracted. Then, the aqueous layer was extracted with CH2Cl2 (3x 150 mL). The combined organic layers were dried over Na2SO4

, 75 mmol) in ethanol (70 mL) was added p-TsOH·H2O (0.14 g, 0.83 mmol) at room temperature. The mixture was stirred at this temperature for 3 h. Then, the mixture was diluted with water (30 mL) and aqueous saturated NaHCO3 (30 mL), then CH2Cl2 (50 mL) was added and the layers were extracted. Then, the aqueous layer was extracted with CH2Cl2 (3x 50 mL) and Et2O (1x 50 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel

H. Nmr, MHz, issue.500

C. Nmr, MHz, issue.125

, mmol) in CH3CN (4 mL) was added p-TsOH·H2O (36 mg, 0.21 mmol) at room temperature. The reaction mixture was stirred at this temperature for 5 h. The reaction was quenched with sat. NH4Cl. The layers were separated and the aqueous layer extracted with CH2Cl2 (3x 10 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel

H. Nmr, CDCl3): 1.78 (m, 2H), MHz, issue.500

C. Nmr, 3 (CH2), MHz, vol.21, issue.125, p.1

, 2 (CON); 206.5 (CO) ppm, vol.174

, iR (ATR): ? (CO) = 1703, pp.1668-1669

, HRMS (ESI) m/z: C11H15NO2

, Compound 560

, The mixture was allowed to warm to room temperature and was stirred at room temperature for 20 h. Then, the reaction was quenched with sat. NH4Cl (15 mL). The layers were separated and the aqueous layer was extracted with AcOEt (2x 20 mL) and CH2Cl2 (2x 20 mL). The combined organic layers were dried over Na2SO4, THF (6 mL) was added bromovinylmagnesium (0.77 mL, 0.77 mmol, 1 M in THF) at 0 °C

H. Nmr, CDCl3): 1.26 (s, 3H, CH3); 1.68 (m, 2H), MHz, issue.500

C. Nmr, MHz, issue.125

, HRMS (ESI) m/z: C13H19NO2

, 31 mmol) in CH2Cl2 (2 mL) was added pTsOH·H2O (5 mg, 0.03 mmol) at room temperature. The mixture was stirred at room temperature for 15 min. Then, the reaction was quenched with sat. NH4Cl (10 mL). The layers were separated and the aqueous layer was extracted with CH2Cl2 (3x 20 mL). The combined organic layers were dried over Na2SO4

H. Nmr, CDCl3): 1.37 (m, 1H), MHz, vol.1, issue.500

, Hz, 1.0 Hz, 1H); 2.32 (m, 2H); 2.55 (m, 1H); 2.80 (td, J =, vol.9, issue.3

C. Nmr, MHz, CDCl3): 22.2 (CH2); 27.0 (CH2); 29.1 (CH2); 30.2 (CH3), vol.33, p.1

, iR (ATR): ? (CO) = 1699 cm-1

, HRMS (ESI) m/z: C13H19NO

H. Nmr, CDCl3): 1.26 (m, 1H), MHz, vol.1, issue.500

C. Nmr, MHz, CDCl3): 22.9 (CH2); 26.1 (CH2); 29.1 (CH2), vol.30

, 3 (CON) ppm, vol.174

, iR (ATR): ? (CO) = 1699 cm-1

, HRMS (ESI) m/z: C13H19NO

, Compound 531

, To a solution of alkene 524 (0.250 g, 1.26 mmol) and p-methoxyphenyl vinyl ketone (0.513 g, 3.16 mmol) in CH2Cl2 (12 mL) was added Grubbs second-generation catalyst (32 mg

H. Nmr, MHz, issue.500

C. Nmr, MHz, issue.125

, NCHO

, 7 (Cq), =CH, vol.113, issue.2

, iR (ATR): ? (CO) = 1693, pp.1598-1599

, HRMS (ESI) m/z: C19H25NO4 [M + Na

, 21 mmol) was added in small portions to a solution of 1-(4pentenyl)piperidine-2,6-dione (2.9 g, 16.0 mmol) in methanol (80 mL) at 0 °C. The reaction mixture was stirred 3 h at 0 °C and was allowed to warm to room temperature. The mixture was diluted with water (100 mL) and aqueous saturated NaHCO3 (100 mL), then CH2Cl2 (150 mL) was added and the layers were extracted. Then, the aqueous layer was extracted with CH2Cl2 (3x 150 mL). The combined organic layers were dried over Na2SO4, vol.67

, 31 mmol) at room temperature. The mixture was stirred at this temperature for 3 h. Then, the mixture was diluted with water (30 mL) and aqueous saturated NaHCO3 (30 mL), then CH2Cl2 (50 mL) was added and the layers were extracted. Then, the aqueous layer was extracted with CH2Cl2 (3x 50 mL) and Et2O (1x 50 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel, ethanol (62 mL) was added p-TsOH·H2O (0.055 g, 0

H. Nmr, MHz, issue.500

1. Hz and N. ). ,

C. Nmr, MHz, CDCl3): 15.4 (CH3, OCH2CH3), vol.15

, 16 mmol) in H2O (40 mL) was added acrolein (0.94 mL, 13.38 mmol). The reaction mixture was stirred at 50 °C for 16 h. The mixture was allowed to cool to room temperature and AcOEt (50 mL) was added. The layers were separated and the aqueous layer extracted with AcOEt (1x 50 mL) and CH2Cl2 (3x 50 mL). The combined organic layers were dried over Na2SO4

H. Nmr, , vol.2, pp.2-2

C. Nmr, MHz, CDCl3): 25.2 (CH2, CH2-CH2-CHO), vol.35, p.2

, The reaction mixture was stirred at room temperature for 5 min. Then, water (10 mL) and AcOEt (15 mL) were added to the mixture. The layers were separated and the aqueous layer extracted with AcOEt (3x 20 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel, EtOH (6 mL) was added Cs2CO3 (50 mg, 0.15 mmol)

H. Nmr,

C. Nmr, CDCl3): 26.8 (CH2); 31.5 (CH2), MHz, vol.34, issue.125

, HRMS (ESI) m/z: C11H14O3 [M-H

, imidazole (147 mg, 2.1 mmol), DMAP (9 mg, 0.072 mmol). The reaction mixture was stirred at room temperature for 16 h. Then, water (10 mL) was added to the mixture. The layers were separated and the aqueous layer extracted with CH2Cl2 (3x 20 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel, g, 0.36 mmol) in CH2Cl2 (4 mL) was added TBSCl (108 mg, 0.72 mmol)

H. Nmr, s, 3H, SiCH3); 0.05 (s, 3H, SiCH3); 0.84 (s, 9H, SiC(CH3)3); 1.50 (m, 2H, MHz, issue.500

. Hz, CH=C(OTBS), vol.1

C. Nmr, MHz, CDCl3):-4.7 (CH3, Si-CH3);-4.7 (CH3, Si-CH3), vol.17

, )3); 28.1 (CH2); 31.6 (CH2); 34.2 (CH2); 39.2 (CH2); 54.8 (CH, CHCHOTBS); 61.8 (Cq)

, IR (ATR): ? (CO) : 1767, pp.1722-1723

, g, 0.29 mmol) in THF (6 mL) was added bromovinylmagnesium (0.32 mL, 0.32 mmol, 1 M in THF) at 0 °C. The mixture was allowed to warm to room temperature and was stirred at room temperature for 2 h. Then, the reaction was quenched with sat. NH4Cl (15 mL). The layers were separated and the aqueous layer was extracted with AcOEt (2x 20 mL) and CH2Cl2 (2x 20 mL). The combined organic layers were dried over Na2SO4, HRMS (ESI) m/z

H. Nmr, MHz, issue.500

, 42 (m, 1H); 5.88 (m, 2H) ppm

C. Nmr, Si-CH3);-4.5 (CH3, Si-CH3), MHz, CDCl3):-4.7 (CH3, vol.17

, )3); 26.8 (CH2); 27.8 (CH2); 34.5 (CH2), vol.36

, 2193 solution of alkene (+)-685-B (12 mg, 0.035 mmol) in CH2Cl2 (3 mL) was added Grubbs second-generation catalyst (3 mg, 0.0035 mmol) at room temperature. Then, the mixture was stirred at 40 °C for 3h. After concentration under reduced pressure, the crude product was purified by column chromatography on silica gel, HRMS (ESI) m/z: C19H32O3Si [M+H] + calc. 337.2199, found. 337

H. Nmr, MHz, issue.500, p.2

, CH2CO); 2.14 (dt, J = 16.8 Hz, 1.9 Hz, 1H, CH=CH-CH2); 2.58 (d, J = 19.1 Hz, 1H, CH2CO); 2.64 (m, 1H, CHCHOTBS); 2.66 (m, 1H, CH=CH-CH2)

C. Nmr, Si-CH3);-4.5 (CH3, Si-CH3), MHz, CDCl3):-4.7 (CH3, vol.17

, TBSOCH-CH2-CH2), vol.2

, CH=CH-CH2), vol.35

, Cq, COH), vol.88

, IR (ATR): ? (OH) : 3479 cm-1 , ? (CO) : 1723 cm-1 , ? (C=C, pp.771-772

, HRMS (ESI) m/z: C17H28O3Si [M + H] + calc. 309.1886

, Compound 638

, To a solution of 637 (1.8 g, 13.03 mmol) in H2O (40 mL) was added acrolein (1.0 mL, vol.14, p.33

, The reaction mixture was stirred at 50 °C for 16 h. The mixture was allowed to cool to room temperature and AcOEt (50 mL) was added. The layers were separated and the aqueous layer extracted with AcOEt (1x 50 mL) and CH2Cl2 (3x 50 mL). The combined organic layers were dried over Na2SO4

, 67 mmol) in CH2Cl2 (42 mL) was added 1(triphenylphosphoranylidene)-2-propanone (6.05 g, 19 mmol). The reaction mixture was stirred for 20h at room temperature and the solvent was evaporated under reduced pressure. The crude material was purified by silica gel chromatography (petroleum ether / ethyl acetate, 70/30 to 60/40) to afford compound 638, vol.12

H. Nmr, 500 MHz, CDCl3): 1.80 (m, 2H, pp.2-2

2. Hz,

C. Nmr, CDCl3): 26.8 (CH3, C(O)CH3), MHz, issue.125

, 4 (CH2); 60.6 (Cq); 120.5 (=CH2); 130.6 (=CH), vol.36

, 97 mmol) in EtOH (60 mL) was added Cs2CO3 (0.2 g, 0.59 mmol). The reaction mixture was stirred at room temperature for 10 sec. Then, water (100 mL) and AcOEt (100 mL) were added to the mixture. The layers were separated and the aqueous layer extracted with AcOEt (2x 80 mL) and CH2Cl2 (2x 80 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel

H. Nmr, CDCl3): 1.30 (m, 1H); 1.81 (m, 2H); 1.90 (m, 1H); 2.16 (s, 3H, C(O)CH3); 2.31 (m, 2H); 2.46 (m, 3H), MHz, issue.500

C. Nmr, CDCl3): 24.6 (CH2); 30.4 (CH3, C(O)CH3), MHz, vol.31, issue.125

, The reaction mixture was heated to 75 °C for 5 h, after cooling at room temperature the reaction mixture was quenched with sat. NH4Cl. The layers were separated and the aqueous layer was washed with AcOEt (2x 10mL) and CH2Cl2 (2x 10 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure. The crude material was purified by silica gel chromatography, toluene (4 mL) was added n-Bu3P (0.085 mL, 0.34 mmol)

H. Nmr, MHz, vol.5, issue.500

. Hz,

C. Nmr, CDCl3): 24.6 (CH2); 25.2 (CH2); 29.7 (CH3, C(O)CH3); 30.4 (CH), MHz, issue.125

, HRMS (ESI) m/z: C16H20O5 [M + H] + calc. 293.1389

H. Nmr, CDCl3) : 1.63 (m, 1H); 1.80 (m, 1H); 1.97 (m, 1H); 2.11 (s, 3H, C(O)CH3); 2.14 (m, 3H), MHz, issue.500

C. Nmr, CH2); 30.4 (CH3, C(O)CH3); 32.8 (CH2); 34.0 (CH2), MHz, vol.34, issue.125, p.1

, HRMS (ESI) m/z

, 51 mmol) in CH2Cl2 (4 mL) was added Et3N (0.42 mL, 3.09 mmol) and the reaction mixture was stirred for 0.2 h at room temperature. TBSOTf (0.52 mL, 2.26 mmol) was added and the reaction mixture was stirred 1h at room temperature. Then, the reaction mixture was quenched with water, the layers were separated and the aqueous layer was washed with CH2Cl2 (3x 15mL). The combined organic layers were washed with sat. NaHCO3 and were dried over Na2SO4, filtered and concentrated under reduced pressure. The crude material was purified by silica gel chromatography

H. Nmr, MHz, issue.500

, Si-C(CH3)3); 0.94 (s, 9H, Si-C(CH3)3); 1.07 (td, J = 13.2 Hz, 5.6 Hz, 1H), vol.9

, CH=C(OTBS), vol.1

C. Nmr,

, )3); 25.6 (CH3, Si-C(CH3)3); 25.7 (CH3, SiC(CH3)3); 27.6 (CH2)

, HRMS (ESI) m/z

, 44 mmol) and methyl vinyl ketone 15 (0.1 mL, 1.12 mmol) in CH2Cl2 (6 mL) was added Grubbs second-generation catalyst (38 mg, 0.044 mmol) at room temperature. Then, the mixture was stirred at 40 °C for 3h. After concentration under reduced pressure, the crude product was purified by column chromatography on silica gel, vol.86

H. Nmr, MHz, issue.500

. Hz,

1. Hz and C. , 72 (ddd, J = 9.6 Hz, 5.8 Hz, 3.1 Hz, 1H, CHOTBS), vol.3

. Hz, CH=CH=C(O)) ppm, vol.1

C. Nmr,

, )3); 25.6 (CH3, Si-C(CH3)3); 25.7 (CH3, SiC(CH3)3); 26.6 (CH3, C(O)CH3)

, HRMS (ESI) m/z: C25H44O4Si2 [M+H] + calc. 465.2856, found, vol.465, p.2851

, 70 mmol) was added in small portions to a solution of alkene (+)-662 (0.6 g, 1.4 mmol) in methanol (15 mL) at 0 °C. The reaction mixture was stirred 3 h at 0 C and was allowed to warm to room temperature. The mixture was diluted with water (15 mL) and aqueous saturated NaHCO3 (15 mL), then CH2Cl2 (30 mL) was added and the layers were extracted. Then, the aqueous layer was extracted with CH2Cl2 (3x 30 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure. The crude material was purified by silica gel chromatography

H. Nmr, MHz, issue.500

9. and S. , CH3)3); 0.91 (s, 9H, Si-C(CH3)3); 1.08 (m, 1H); 1.47 (m, 2H), CH=C(OTBS), vol.1

C. Nmr, Si-C(CH3)3); 18.0 (Cq, Si-C(CH3)3); 22.1 (CH2); 25.6 (CH3, SiC(CH3)3), MHz, vol.25, issue.125

, HRMS (ESI) m/z

, 668 (0.1 g, 0.23 mmol) in CH2Cl2 (4 mL) was added Et3N (65 µL, 0.47 mmol) and the reaction mixture was stirred for 0.2 h at room temperature. TBSOTf (81 µL, 0.35 mmol) was added and the reaction mixture was stirred

, The combined organic layers were washed with sat. NaHCO3 and were dried over Na2SO4, filtered and concentrated under reduced pressure. The crude material was purified by silica gel chromatography, Then, the reaction mixture was quenched with a solution of HCl 10 % in water, the layers were separated and the aqueous layer was washed with CH2Cl2 (3x 10mL)

H. Nmr, MHz, issue.500

, )3); 1.13 (ddt, J = 12.3 Hz, 6.1 Hz, 1.5 Hz, 1H, TBSOCH-CH2-CH2), vol.1

1. Hz and T. , 27 (ddt, J = 14.1 Hz, 6.1 Hz, 1.6 Hz, vol.1, pp.2-2

C. Nmr, Si-CH3), MHz, CDCl3):-4.9, vol.3

, Cq, Si-C(CH3)3), vol.17

, TBSOCH-CH2-CH2), vol.26

C. H. and C. , 1 (CH, CHOTBS), vol.74, p.9

, HRMS (ESI) m/z

, To a solution of alkene (+)-670 (0.270 g, 0.63 mmol) and methyl vinyl ketone 15 (0.12 mL, 1.58 mmol) in CH2Cl2 (6 mL) was added Grubbs second-generation catalyst (54 mg

, mmol) at room temperature. Then, the mixture was stirred at 40 °C for 3h. After concentration under reduced pressure, the crude product was purified by column chromatography on silica gel

H. Nmr, MHz, issue.500

C. Nmr, )3); 18.0 (Cq, Si-C(CH3)3), MHz, vol.17, issue.125

, Cq); 66.1 (CH, CHOTBS), vol.74, p.1

, HRMS (ESI) m/z

, 21 mmol) in toluene (2 mL) was added n-Bu3P (53 µL, 0.21 mmol). The reaction mixture was stirred to room temperature for 72 h, then the reaction mixture was quenched with addition of sat. NH4Cl. The layers were separated and the aqueous layer was washed with AcOEt (2x 10mL) and CH2Cl2 (2x 10 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure. The crude material was purified by silica gel chromatography

H. Nmr, MHz, issue.500

C. Hz and . Ppm,

C. Nmr, MHz, issue.125

C. H. and C. , Cq); 67.4 (CH, CHOTBS); 77.8 (CH, CHOTBS), vol.54

, HRMS (ESI) m/z: C25H46O4Si2 [M+K] + calc. 505.2572, found. 505, p.2566

, 26 mmol) in TFH (6 mL) was added a solution of TBAF (0.51 mL, 0.51 mmol, 1 M in THF). The reaction mixture was stirred to room temperature for 0.5 h, then the reaction mixture was quenched with addition of water (10 mL). The layers were separated and the aqueous layer was washed with AcOEt (2x 10mL) and CH2Cl2 (2x 10 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure. The crude material was purified by silica gel chromatography

H. Nmr, s, 3H, SiCH3); 0.05 (s, 3H, SiCH3); 0.87 (s, 9H, SiC(CH3)3); 1.25 (m, 2H, MHz, issue.500

C. Nmr, MHz, issue.125

, )3); 26.1 (CH2); 28.2 (CH2); 36.1 (CH2); 38.1 (CH2); 42.8 (CH, CHOHCHCH); 53.5 (Cq), vol.65

, 2037 mp: 78.5 °C To a solution of alkene (+)-680 (0.250 g, 0.80 mmol) and methyl vinyl ketone 15 (0.16 mL, 2.01 mmol) in CH2Cl2 (8 mL) was added Grubbs second-generation catalyst (69 mg, HRMS (ESI) m/z

, mmol) at room temperature. Then, the mixture was stirred at 40 °C for 3h. After concentration under reduced pressure, the crude product was purified by column chromatography on silica gel

H. Nmr, SiCH3); 0.83 (s, 9H, SiC(CH3)3); 1.25 (m, 2H); 1.81 (m, 1H); 1.95 (m, 2H); 2.18 (s, 3H, C(O)CH3); 2.26 (m, 1H), MHz, issue.500, p.3

C. Nmr, , vol.17

, C(O)CH3); 28.1 (CH2); 34.6 (CH2); 38.1 (CH2); 43.1 (CH, HCOHCHCH); 53.8 (Cq)

, HRMS (ESI) m/z

, To a solution of alkene (+)-648 (0.178 g, 0.91 mmol) and methyl vinyl ketone 15 (0.19 mL, 2.29 mmol) in CH2Cl2 (10 mL) was added Grubbs second-generation catalyst (78 mg

, mmol) at room temperature. Then, the mixture was stirred at 40 °C for 3h. After concentration under reduced pressure, the crude product was purified by column chromatography on silica gel

H. Nmr, 18 (s, 3H, C(O)CH3); 2.30 (m, 1H); 2.48 (m, 3H); 2.98 (d, J = 19.2 Hz, 1H), 500 MHz, CDCl3): 1.58 (m, 2H); 1.82 (m, 2H); 2.07 (m, 1H), vol.2

C. Nmr, CDCl3): 26.8 (CH2); 27.1 (CH3, C(O)CH3); 30.2 (CH2), MHz, vol.34, issue.125

, 3 (Cq); 73.4 (OCH), vol.38

, HRMS (ESI) m/z

, 12 mmol) in toluene (3 mL) was added n-Bu3P (30 µL, 0.12 mmol). The reaction mixture was stirred to room temperature for 30 days, then the reaction mixture was quenched with sat. NH4Cl. The layers were separated and the aqueous layer was washed with AcOEt (2x 10mL) and CH2Cl2 (2x 10 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure. The crude material was purified by silica gel chromatography

H. Nmr, MHz, issue.500

, )3); 1.49 (m, 1H); 1.69 (m, 1H)

C. Nmr, MHz, issue.125

, )3); 22.4 (CH2); 25.8 (CH3, Si-C(CH3)3); 28.6 (CH2), CHOTMS

, CH=C-C(O)); 152.6 (CH=C-C(O)), vol.151

, RMS (ESI) m/z: C21H38O4Si2 [M+Na] + calc. 433.2207