Y. H. Teng, Synthesis of Novel Fused Tropones and Colchicinoids Through Rh(I)-Catalyzed [2+2+2+1] Cycloaddition of Triynes with Carbon Monoxide Ph, 2011.

X. Liu, Y. J. Hu, B. Chen, L. Min, X. S. Peng et al., Org. Lett, p.4612, 2017.

J. E. Baldwin, J. Chem. Soc. Chem. Commun, p.734, 1976.

G. Blond, C. Bour, B. Salem, and J. Suffert, Org. Lett, p.1075, 2008.

C. Hulot, G. Blond, and J. Suffert, J. Am. Chem. Soc, vol.130, p.5046, 2008.

C. Hulot, S. Amiri, G. Blond, P. R. Schreiner, and J. Suffert, J. Am. Chem. Soc, p.16587, 2009.

M. Charpenay, A. Boudhar, G. Blond, and J. Suffert, Angew. Chem. Int. Ed, p.4379, 2012.

S. Blouin, V. Gandon, G. Blond, and J. Suffert, Angew. Chem. Int. Ed, vol.55, p.7208, 2016.

J. Joussot, A. Schoenfelder, J. Suffert, and G. Blond, Comptes Rendus Chim, p.665, 1920.

T. Kang, K. L. White, T. J. Mann, A. H. Hoveyda, and M. Movassaghi, Angew. Chem. Int. Ed, vol.56, p.13857, 2017.

W. H. Chiou, A. Schoenfelder, L. Sun, A. Mann, and I. Ojima, J. Org. Chem, p.9418, 2007.

E. Airiau, T. Spangenberg, N. Girard, A. Schoenfelder, J. Salvadori et al., Chem. Eur. J, vol.14, p.10938, 2008.

E. Airiau, N. Girard, M. Pizzeti, J. Salvadori, M. Taddei et al., J. Org. Chem, p.8670, 2010.

Y. Shibata and K. Tanaka, Synthesis (Stuttg). 2012, 44, 323. H. Morita, J. Nat. Prod, vol.78, p.1656, 2015.

F. He, Y. Bo, J. D. Altom, and E. J. Corey, J. Am. Chem. Soc, p.6771, 1999.

J. Xie, A. L. Wolfe, and D. L. Boger, Org. Lett, p.868, 2013.

G. I. Elliott, J. Velcicky, H. Ishikawa, Y. Li, and D. L. Boger, Angew. Chem. Int. Ed, p.620, 2006.

D. Kato, Y. Sasaki, and D. L. Boger, J. Am. Chem. Soc, p.3685, 2010.

J. P. Lajiness, W. Jiang, and D. L. Boger, Org. Lett, p.14, 2012.

J. E. Sears, T. J. Barker, and D. L. Boger, Org. Lett, p.5460, 2015.

I. Coldham, A. J. Burrell, L. E. White, H. Adams, and N. Oram, Angew. Chem. Int. Ed, vol.46, p.6159, 2007.

T. Ishikawa, K. Kudo, K. Kuroyabu, S. Uchida, T. Kudoh et al., J. Org. Chem, p.7498, 2008.

S. H. Tan, M. G. Banwell, A. C. Willis, and T. A. Reekie, Org. Lett, p.5621, 2012.

J. M. Janey, C. J. Orella, E. Njolito, J. M. Baxter, J. D. Rosen et al.,

I. W. Kowal and . Davies, J. Org. Chem, p.3212, 2008.

M. Lounasmaa and A. Tolvanen, Alkaloids, vol.42, 1992.

M. F. Bartlett and W. I. Taylor, J. Am. Chem. Soc, vol.82, p.5941, 1960.

M. E. Kuehne, J. Am. Chem. Soc, 1964.

D. B. England and A. Padwa, J. Org. Chem, p.2795, 2008.

L. Salacz, C. Charpentier, J. Suffert, and N. Girard, J. Org. Chem, p.2257, 2017.

J. A. Pigza, J. Han, A. Chandra, D. Mutnick, M. Pink et al., J. Org. Chem, p.822, 2013.

D. Martin, S. Kehrli, M. D'augustin, H. Clavier, M. Mauduit et al., J. Am. Chem. Soc, vol.128, p.8416, 2006.

H. Hénon, M. Mauduit, and A. , Angew. Chem. Int. Ed, p.9122, 2008.

W. Bartmann, E. Guntrum, H. Urbach, and J. Wunner, Synth. Commun, vol.18, p.711, 1988.

C. L. Kingsbury, K. S. Sharp, and R. A. Smith, Tetrahedron, vol.55, p.14693, 1999.

A. S. Vellekoop and R. A. Smith, Tetrahedron, vol.54, p.11971, 1998.

D. J. Collins and J. D. Cullen, Aust. J. Chem, p.735, 1988.

H. Irikawa, S. Mutoh, M. Uehara, and Y. Okumura, Bull. Chem. Soc. Jpn, vol.62, p.3031, 1989.

Y. Ito, T. Hirao, and T. Saegusa, J. Org. Chem, p.1011, 1978.

Y. Lu, P. L. Nguyen, N. Lévaray, and H. Lebel, J. Org. Chem, p.776, 2013.

K. C. Nicolaou, D. Pappo, K. Y. Tsang, R. Gibe, and D. Y. Chen, Angew. Chem. Int. Ed, vol.47, p.944, 2008.

J. Zhang, H. Shi, Y. Ma, and B. Yu, Chem. Commun, vol.48, p.8679, 2012.

X. Zhao, W. Li, J. Wang, and D. Ma, J. Am. Chem. Soc, p.2932, 2017.

B. M. Stoltz, T. Kano, and E. J. Corey, J. Am. Chem. Soc, vol.122, p.9044, 2000.

K. Kakiuchi, M. Takeda, Y. Tobe, and Y. Odaira, Chem. Lett, p.305, 1985.

I. I. Popadyuk, A. V. Markov, O. V. Salomatina, E. B. Logashenko, A. V. Shernyukov et al.,

N. F. Zenkova and . Salakhutdinov, Bioorganic Med. Chem, p.5022, 2015.

K. Ravindar, P. Y. Caron, and P. Deslongchamps, J. Org. Chem, p.7979, 2014.

F. Oueslati, G. Dupas, and L. Barre, Org. Lett, p.153, 2007.

S. R. Harutyunyan, F. ??pez, W. R. Browne, A. Correa, D. Pe??a et al., J. Am. Chem. Soc, vol.128, p.9103, 2006.

P. Cottet, M. Daniel, and A. , Org. Lett, p.828, 2013.

. I-195a, 2-(hept-1-yn-1-yl)-1-(4-hydroxybut-2-yn-1-yl)cyclohex-2-en-1-ol

, I-195a was synthesised following general procedure II using I-196a (276.5 mg, 1.2 mmol, 1 eq.), paraformaldehyde (113.8 mg, 1.2 mmol, 1 eq, EtMgBr 40%, p.5

, THF (11.6 mL). Work-up and purification afforded I-195a as a clear oil in 74% yield

, 81.1 (C17), 77.6 (C7), 70.3 (C1), 51.4 (C18), vol.33

. I-195b, 1-(4-hydroxybut-2-yn-1-yl)-2-((trimethylsilyl)ethynyl)cyclohex-2-en-1-ol

, I-195b was synthesised following general procedure II using I-196b (250 mg, 1.076 mmol, 1 eq.), paraformaldehyde (102 mg, 1.076 mmol, 1 eq, EtMgBr 40%, p.5

, 8 mL). Work-up and purification afforded I-195b as a clear oil in 83% yield (233.2 mg, 0.889 mmol)

, MHz, CDCl3): ? 6.31 (t, J = 4.0 Hz, 1H, H3), 4.28 (bs, 2H, H18), 2.87, 2.54 (ABq J = 16.6 Hz, 2H, H15), 2.27 (bd, J = 10.2 Hz, 1H, H19), 2.15 (m, 2H, H4), 1.90 (m, 2H, H6), 1.76 (m, 1H, H5), 1.63 (m, 1H, H5'), vol.1

, Experimental Data -Part I (m, 1H, H6'), 1.79 (m, 1H, H5'), 1.14 (t, J = 7.5 Hz, 3H, H24) 13 C NMR (100 MHz, CDCl3): ? 208.5 (C7), vol.128

. I-199a, 10-hexahydro-9aH-fluoreno[1,2-c]furan-9a-ol See synthesis of I-194a, vol.4, 2009.

, 11 (s, 2H, H20), 5.09, 5.01 (ABq J = 11.8 Hz, 2H, H18), 2.86, 2.76, ABq J = 17.0 Hz, 2H, H15), 2.75 (m, 2H, H9), 2.61 (m, 1H, H23), 2.51 (m, 1H, H23'), 2.41 (m, 1H, H4), vol.5

. Hz, 3H, H13) 13 C NMR (100 MHz, CDCl3): ? 143.8 (C16), 137.9 (C21), 137.3 (C2), 136.4 (C8), 134.5 (C22), 133.3 (C17), 133.0 (C7), 123.6 (C3), vol.76

. I-199c,

, See synthesis of I-194c

, 07 (s, 3H, H14), 2.98 (d, J = 16.4 Hz, 1H, H15), 2.77 (m, 2H, H9), 2.64-2.47 (m, 3H, H15', H23), 2.43 (m, 1H, H4), 2.36 (m, H6), 2.24 (m, H4'), 1.90 (m, 1H, H5), 1.70, vol.3

, 132.4 (C16), 124.7 (C3), 81.2 (C1), 73.4 (C18), 73.1 (C20), 50.7 (C14), vol.39

, Hz, 2H, H23), 2.06 (t, J = 7.2 Hz, 4H, H4, H9), 1.87 (m, 2H, H6), 1.76 (m, 1H, H5), 1.53 (m, 1H, H5'), 1.42 (m, 2H, H10), 1.30 (m, 4H, H11, H12), 1.15 (t, J = 7.2 Hz, 3H, H24), 0.89 (bt, J = 6.8 Hz, 3H, H13) 13 C NMR (100 MHz, CDCl3, vol.28

. Calculated-for, , vol.878, p.547, 1036.

. I-201p, -phenylprop-2-yn-1-yl)oxy)but-2-yn-1-yl)benzenesulfonamide

, Compound I-201p was obtained following general procedure III using compound I-203e (193 mg

, mL, 1.4 mmol, 3 eq.), tetrabutylammonium hydrogen sulfate (15.8 mg, 0.047 mmol, 0.1 eq, DCM (2.5 mL), and NaOH 50%

, MHz, CDCl3) : 7.83 (d, J = 8.4 Hz, 2H, H26), 7.44 (m, 2H, H24), 7.32 (m, 3H, H30, H31), 7.26 (d, J = 8.4Hz, 1H, H25), 7.25 (d, J = 8.4Hz, 1H, H25'), vol.6

, C6), 28.7 (C10), 25.6 (C4), 22.4 (C12), 21.7 (C29), 21.1 (C5, vol.19, p.547, 1036.

, -(hept-1-yn-1-yl)cyclohex-2-en-1-yl)oxy)but-2-yn-1-yl)-4-methyl-N-(prop-2-yn-1-yl)benzenesulfonamide

, Triyne I-201r was prepared following general procedure X using a solution of diethyl 2-(pent-2-yn-1

, malonate I-216 (35 mg, 0.155 mmol, 1 eq.) in dry THF (0.6 mL), a suspension of NaH (7.4 mg, pp.0-186

, eq.) in dry THF (0.6 mL) and a solution of propargyl bromide I-213a (50 mg, 0.155 mmol, p.1

, Work-up and purification afforded triyne I, dry THF (0.6 mL)

, Rf = 0.55 (pentane:AcOEt 9:1) 1 H NMR (400 MHz, CDCl3): ? 6.17

, C8), 85.3 (C21), 81.0 (C7), 80.7 (C16), 80.1 (C17), 73.7 (C22), 73.2 (C1), vol.61

, ppm) IR: ? 2932, vol.858, p.669, 0914.

. I-201s, -(hept-1-yn-1-yl)cyclohex-2-en-1-yl)undeca-3,8-diyne-1,1,6, vol.1, p.6

, Triyne I-201s was prepared following general procedure X using a solution of diethyl 2-(pent-2-yn-1

, 477 mmol, 1.2 eq.) in dry THF (1.54 mL), a suspension of NaH (19.1 mg, 0.477 mmol, 1.2 eq.) in dry THF (1.54 mL) and a solution of propargyl bromide I-213f

. Mhz, CDCl3): ? 143.6 (C28), 137.4 (C3), 136.0 (C25), 129.5 (2C, C26), 127.7 (2C, C27), vol.121

, HRMS: (ESI)+ Calculated for

, -(hept-1-yn-1-yl)cyclohex-2-en-1-yl)oxy)but-2-yn-1-yl)oxy)acetonitrile, ppm) IR: ? b3285, vol.659, 1064.

, Compound I-201u was obtained following general procedure III using alcohol I-203a (566 mg, vol.2, p.17

, bromoacetonitrile (0.19 mL, 2.609 mmol, 1.2 eq.), tetrabutylammonium hydrogen sulfate (73.8 mg, 0.217 mmol, 0.1 eq, DCM (9 mL), and NaOH 50%

, Rf = 0.45 (pentane:AcOEt 9:1) 1 H NMR (400 MHz, CDCl3): ? 6.18 (bs, 1H, H3)

. Hz, 3H, H24), 0.90 (t, J = 7.2 Hz, 3H, H13) 13 C NMR (100 MHz, CDCl3): ? 137.7 (C3), vol.121

, C8), 86.0 (C17), 80.8 (C7), 78.8 (C16), 73.7 (C1, vol.31

, 3 (C5), vol.17, p.572, 1136.

. I-202a, 3-ethyl-1-pentyl-6,7,8a, vol.9, p.11

, Compounds I-202a and I-206a were obtained following the general protocol VI using triyne I-201a (50 mg, 0.153 mmol, 1 eq.), [Rh(COD)Cl]2 (3.8 mg, 0.008 mmol, 5 mol%)

, pentane:AcOEt 8:2) 1 H NMR (400 MHz, CDCl3): ? 5.82 (bs, 1H, H3, vol.13

. Hz,

. Hz, C20), 136.8 (C16), 135.7 (C7), 135.4 (C17), 131.1 (C3), 74.1 (C20), 73.3 (C18), 73.2 (C1), vol.143, p.946, 1075.

, I-202b. 1-pentyl-6,7,8a, vol.9, p.11

, Purification yielded I-202b as a white amorphous solid with 53% yield (0.089 mmol, 29.0 mg) and I-206b as yellow oil with 38% yield, Compounds I-202b and I-206b were obtained following the general protocol VI using triyne I-201b (50 mg, 0.168 mmol, 1 eq.)

, 99 (m, 1H, H9), 2.65 (bt, J = 10.6 Hz, 1H, H9'), 2.23 (bs, 2H, H4), 1.99 (m, 1H, H6), 1.85 (m, 1H, H5), 1.78-1.67 (m, 2H, H6', H5'), 1.58 (m, 1H, H10), 1.31 (m, 5H, H10', H11, H12), 0.87 (bs, 3H, H13) 13 C NMR (100 MHz, CDCl3): ? 186.2 (C=O), vol.13

. I-202f, -nitrophenyl)-1-pentyl-6,7,8a, vol.9, p.11

, Compounds I-202f and I-206f were obtained following the general protocol VI using triyne I-201f (50 mg, 0.119 mmol, 1 eq.), [Rh(COD)Cl]2 (2.9 mg, 0.006 mmol, 5 mol%)

1. Hz, 1H, H9), 2.27 (bs, 2H, H4), 2.03 (m, 1H, H6), 1.91 (m, 1H, H5, vol.144

, 1 (C24), 139.6 (C23), 139.6 (C16), 137.7 (C17), 135.5 (C28), 135.4 (C25), 135.3 (C3), 131.8 (C3), 129.5 (C27), vol.124, p.730, 0910.

. I-202g, 3-(4-methoxyphenyl)-1-pentyl-6,7,8a, vol.9, p.11

, Purification yielded I-202g as a Experimental Data white amorphous solid with 43% yield (0.053 mmol, 23.0 mg), and I-206g as yellow oil with 46% yield, Compounds I-202g and I-206g

2. Hz, , vol.142

, 2C, C25), 75.1 (C20), 73.5 (C1), 73.0 (C18), 63.8 (C15), 55.5 (C29), vol.33

, 8 (C5), 14.2 (C13) HRMS: (ESI)+ Calculated for, C4), 22.5 (C12, vol.19, p.829, 1033.

. I-202h, -methoxyphenyl)-1-pentyl-6,7,8a, vol.9, p.11

, Compounds I-202h and I-206h were obtained following the general protocol VI using triyne I-201h (50 mg, 0.124 mmol, 1 eq.), [Rh(COD)Cl]2 (3.1 mg, 0.006 mmol, 5 mol%)

, MHz, CDCl3): ? 7.30 (m, 1H, H27), vol.6

, Experimental Data -Part I

. Calculated-for, found : 433.2368 (Diff. : 1.22 ppm) IR: ? 2925, vol.773, p.695, 0918.

. I-202i, 1-pentyl-3-(thiophen-2-yl)-6,7,8a, vol.9, p.11

I. Compounds and I. , were obtained following the general protocol VI using triyne I-201i (50 mg, 0.132 mmol, 1 eq.), [Rh(COD)Cl]2 (3.2 mg, 0.007 mmol, 5 mol%)

. Hz, 1H, H25), 6.98 (bs, 1H, H24 or H26), 5.80 (bs, 1H, H3), 5.10, 4.92 (ABq , J = 13.9 Hz, 2H, H20, vol.137

, C17), 134.9 (C2), 134.7 (C16), 131.6 (C22), 130.8 (C3), 130.0 (C24 or C26, vol.128

, Experimental Data HRMS: (ESI)+ Calculated for, (C4), 22.5 (C12), 19.8 (C5), 14.1 (C13) HRMS: (ESI)+ Calculated for [C25H29O3S] + : 409.1837, found : 409.1827 (Diff. : 1.23 ppm) IR: ? 2924, vol.704, p.778, 1051.

. I-202m, -((tert-butyldimethylsilyl)oxy)ethyl)-3-phenyl-6,7,8a, vol.9, p.11

, Compounds I-202m and I-206m were obtained following the general protocol VI using triyne I-201m (50 mg, 0.108 mmol, 1 eq.), [Rh(COD)Cl]2 (2.7 mg, 0.005 mmol, 5 mol%)

, MHz, CDCl3): ? 7.38 (m, 3H, H26, H25), 7.25 (m, 2H, H24), vol.6

1. Hz,

, 132.6 (C3), vol.128

, 62.7 (C10), 37.4 (C9), 27.8 (C6), vol.26

, ppm) IR: ? 2926, p.699, 1079.

. I-202n, , vol.1, p.11

, Compounds I-202n and I-206n were obtained following the general protocol VI using triyne I-201n (50 mg, 0.132 mmol, 1 eq.), [Rh(COD)Cl]2 (3.2mg, 0.007 mmol, 5 mol%)

, Rf = 0.26 (pentane:AcOEt 8:2) 1 H NMR (400 MHz, CDCl3): ? 7.37 (m, 2H, Harom), 7.32 (m, 3H, Harom), 7.26 (m, 2H, Harom), 7.17 (m, 3H, Harom), 5.43 (bs, 1H, H3), vol.137, pp.128-131

, C12 or C26), 75.2 (C20), 73.9 (C1), 73.3 (C18), vol.127

, 3 (C5) HRMS: (ESI)+ Calculated for, vol.25, p.648, 1074.

. I-202o, 3-ethyl-1-pentyl-8-tosyl-7,8,8a, vol.9

I. Compounds and I. , were obtained following the general protocol VI using triyne I-201o (50 mg, 0.104 mmol, 1 eq.), [Rh(COD)Cl]2 (2.6 mg, 0.005 mmol, 5 mol%)

2. Hz, , vol.143

, 142.7 (C7), 142.2 (C21), 136.2 (C17), 135.5 (C25), 134.4 (C2), vol.133

, 3 (C24) HRMS: (ESI)+ Experimental Data Calculated for, C23), 25.6 (C4), 22.5 (C12), 21.6 (C29), 20.7 (C5, vol.14, p.547, 1035.

, I-202p. 1-pentyl-3-phenyl-8-tosyl-7,8,8a,9, vol.10

, were obtained following the general protocol VI using triyne I-201p (50 mg, 0.095 mmol, 1 eq.), [Rh(COD)Cl]2 (2.3 mg, 0.005 mmol, 5 mol%), Compounds I-202p and I-206p

, pentane:AcOEt 8:2) 1 H NMR (400 MHz, CDCl3): ? 7.39 (m, 5H, H27, H30, H31), vol.7

. Hz, 2H, H22), 7.04 (d, J = 8.0 Hz, 2H, H26), 5.72 (bs, 1H, H3), 5.00, 4.83 (ABq, J = 13.7 Hz, 2H, H18

C. Mhz, , vol.137

, C1), 45.8 (C15), 34.1 (C9), 32.5 (C11), 30.1 (C6), 30.0 (C10, C23), 136.2 (C17), 135.7 (C16), 135.1 (C25), 134.2 (C2), 131.5 (C3), 129.6 (2C, C26), 128.8 (2C, C30), 128.5 (2C, C22, vol.128, 0811.

, I-202q. 1-pentyl-5-tosyl, vol.10, pp.11-13, 2009.

, Compounds I-202q and I-206q were obtained following the general protocol VI using triyne I-201q (50 mg, 0.111 mmol, 1 eq.), [Rh(COD)Cl]2 (2.7 mg, 0.006 mmol, 5 mol%)

2. Hz, , vol.143

, 5 (C5), 14.0 (C13) HRMS: (ESI)+ Calculated for, ppm) IR: ? 2924, vol.22, 1070.

. I-202r, diethyl 3-ethyl-2-oxo-1-pentyl, vol.10, pp.11-16, 2009.

, Compounds I-202r and I-206r were obtained following the general protocol VI using triyne I-201r (50 mg, 0.107 mmol, 1 eq.), [Rh(COD)Cl]2 (3.8 mg, 0.008 mmol, 5 mol%)

, 3.53, 3.38 (ABq, J = 16.8 Hz, 2H, H20), 3.38, 3.25 (ABq, J = 16, 2H, H18), 3.04 (m, 1H, H9), 2.74 (m, 1H, H23), 2.49 (m, 2H, H9', H23'), 2.19 (bs, 2H, H4), 1.97 (m, 1H, H6), 1.87 (m, 1H, H5), 1.71 (m, 2H, H6', H5'), 1.50 (m, 1H, H10), 1.30 (m, 5H, H10, vol.8

, 6 (C11), 30.5 (C10), C20), 40.0 (C18, vol.33

, 4 (C24) HRMS: (ESI)+ Calculated for, found : 497.2905 (Diff. : -1.43 ppm) IR: ? 2930, vol.13, 0917.

. I-202s, diethyl 3-ethyl-2-oxo-1-pentyl, vol.10, pp.11-16, 2009.

, Compounds I-202s and I-206s were obtained following the general protocol VI using triyne I-201s (50 mg, 0.082 mmol, 1 eq.), [Rh(COD)Cl]2 (3.8 mg, 0.008 mmol, 5 mol%)

, MHz, CDCl3): ? 5.51 (bs, 1H, H3), 4.26-4.11 (m, 6H, H26, H29), 3.95 (m, 1H, H29), 3.87 (m, 1H, H29'), 3.59 (bd, 1H, H1), 3.44 (m, 4H, H18, H20)

3. Hz and J. H27)-;-t, C28), 170.2 (C28), 147.1 (C8), 145.9 (C17), 145.2 (C22), 143.3 (C21, 3H, H27), 0.90 (t, J = 7.1 Hz, 3H, H24), 0.86 (t, J = 7.1 Hz, 3H, H13) 13 C NMR (100 MHz, CDCl3): ? 189.1 (C=O), 171.2 (C25), 171.0 (C25), vol.1, 0913.

, EtMgBr 40% in 2-methylTHF (5.10 mL, 17.450 mmol, 5 eq.), THF (35 mL) and paraformaldehyde (440 mg, 4.641 mmol, 1.33 eq.). Work-up and purification afforded propargyl alcohol I, Compound I-203a was obtained following general procedure II using compound I-204a (803.8 mg, 3.490 mmol, 1 eq.)

C. Nmr, MHz, CDCl3): ? 137.6 (C3), vol.122

, 3 (C6), 26.0 (C4), 22.4 (C10), 57.5 (C15), 51.5 (C18), 31.3 (C9), 28.8 (C11), vol.28, p.501, 1068.

. I-203c, tyldimethylsilyl)oxy)but-1-yn-1-yl)cyclohex-2-en-1-yl)oxy)but-2-yn-1-ol, vol.4, p.4

, EtMgBr 40% in 2-methylTHF (2.07 mL, 7.079 mmol, 5 eq.), THF (14 mL) and paraformaldehyde (178.6 mg, 1.883 mmol, 1.33 eq.). Work-up and purification afforded propargyl alcohol I, Compound I-203c was obtained following general procedure II using compound I-204c (451.0 mg, 1.416 mmol, 1 eq.)

, Hz, 2H, H9), 2.13 (m, 1H, H4), 2.03 (m, 1H, H4'), 1.86 (m, 1H, H6), vol.84

, 1 (C7), 73.6 (C1), vol.82

, Experimental Data -Part I found : 349.2186 (Diff. : 2.22 ppm) IR: ? 3406, vol.17, p.666, 1007.

. I-203d, -(phenylethynyl)cyclohex-2-en-1-yl)oxy)but-2-yn-1-ol, vol.4

, EtMgBr 40% in 2-methylTHF (2.67 mL, 9.132 mmol, 5 eq.), THF (18 mL) and paraformaldehyde (234.3 mg, 2.429 mmol, 1.33 eq.). Work-up and purification afforded propargyl alcohol I, Compound I-203d was obtained following general procedure II using compound I-204d (431.0 mg, 1.826 mmol, 1 eq.)

, Rf = 0.10 (pentane:AcOEt 9:1) 1 H NMR (400 MHz, CDCl3): ? 7.45 (m, 2H, H10), 7.29 (m, 3H, H11, H12), 6.37 (bs, 1H, H3)

, 123.6 (C9), 121.7 (C2), vol.89

, Compound I-203e was obtained following general procedure II using compound I-204e (100 mg, p.235

, EtMgBr 40% in 2-methylTHF (0.34 mL, 1.173 mmol, 5 eq.), THF (2.4 mL) and paraformaldehyde (29.6 mg, 0.312 mmol, 1.33 eq.). Work-up and purification afforded propargyl alcohol I

, Rf = 0.64 (pentane:AcOEt 7:3) 1 H NMR (400 MHz, CDCl3): ? 7.80 (d, J = 7.2 Hz, 2H, H26), 7.25 (d, J =, vol.7

2. Hz, 1.87 (m, 2H, H6), 1.75 (m, 1H, H5), 1.53 (m, 1H, H5'), 1.38 (m, 2H, H10), 1.28 (bs, 4H, H11, H12), 0.87 (bs, 3H, H13) 13 C NMR (100 MHz, CDCl3): ? 143, vol.21

, 3 (C9), 14.1 (C13) HRMS: (ESI)+ Calculated for, vol.20, p.547, 1036.

. I-203f, -(hept-1-yn-1-yl)cyclohex-2-en-1-yl)-2-(4-hydroxybut-2-yn-1-yl)malonate, vol.2

, M) under argon, a solution of malonate I-211 (603.4 mg, 1.804 mmol, 1 eq.) in dry DMF (4 mL, 0.47 M) was added dropwise. The mixture was allowed to reach room temperature and stirred for 30 min. Then a solution of 2-((4-chlorobut-2-yn-1-yl)oxy)tetrahydro-2H-pyran (408.4 mg, 2.165 mmol, 1.2 eq.) in dry DMF (2 mL, 0.94 M) was added, followed by NaI (324 mg, 2.165 mmol, and the mixture was stirred at room temperature for 22 h. The mixture was quenched with 1 M HCl, then extracted 2 times with DCM. The organics were dried over MgSO4 and the solvent was removed in vacuo. The crude was used in the following deprotection reaction without further purification, 0 °C in dry DMF (10 mL, 0.19

M. , 2 mg, 0.280 mmol, 0.2 eq.) was added. The mixture was stirred at room temperature for 1 day, then washed diluted with water and washed 3 times with Et2O. The crude was purified by flash chromatography (pentane:AcOEt 9:1) to yield I, vol.53

, 3.12 (dt, J = 17.0, 2.1 Hz, 1H, H15), 3.01 (dt, system, MHz, CDCl3): ? 6.17 (bs, 1H, H3), 4.19 (m, 6H, H18, H29), 3.30 (m, 1H, H1)

. Mhz, CDCl3): ? 170.0 (C28), 169.7 (C28'), 138.7 (C3), 121.4 (C2), 90.4 (C8), 83.7 (C17), vol.81

, (ESI)+ Calculated for, 85.6 (C7), 82.1 (C8), 80.8 (C16), 74.0 (C17), 73.6 (C1), vol.62, p.664, 1069.

I. , -(prop-2-yn-1-yloxy)cyclohex-1-en-1-yl)ethynyl)benzene

, 3 mg, 1.959 mmol, 1 eq.), two times propargyl bromide (0.68 mL, 6.267 mmol, 3.2 eq.), tetrabutylammonium hydrogen sulfate (122.1 mg, 0.352 mmol, 0.2 eq, Compound I-204d was obtained following general procedure III using compound I-205d, vol.388

, 1H, H17), 2.24 (m, 1H, H4), 2.10 (m, 1H, H4'), 1.95 (m, 1H, H6), 1.80-1.68 (m, 2H, H6', H5), 1.61 (m, 1H, H5') 13 C NMR (100 MHz, CDCl3): ? 139.4 (C3), 131.7 (2C, C10), vol.128, p.633, 1071.

. I-204e, N-(2-(hept-1-yn-1-yl)cyclohex-2-en-1-yl)-4-methyl-N-(prop-2-yn-1-yl)benzenesulfonamide

, 12 mmol, 1.2 eq.), dry THF (15 mL), DEAD (0.50 mL, 3.12 mmol, 1.2 eq.), N-(but-3-yn-1-yl)-4-methylbenzenesulfonamide (598.5 mg, 2.86 mmol, 1.1 eq.) and a solution of alcohol I-205a, Compound I-204e was obtained following general procedure IX using PPh3 (826.6 mg, vol.3

, Work-up and purification afforded the diyne I-204e quantitatively as a clear oil (3.12 mmol, 1195 mg), dry THF (5 mL)

, Rf = 0.64 (pentane:AcOEt 9:1) 1 H NMR (400 MHz, CDCl3): ? 7.82 (d, J = 7.2 Hz, 2H, H26), 7.25 (d, J =, vol.7

2. Hz, , p.13

C. Nmr, MHz, CDCl3): ? 143.0 (C28), 139.7 (C3), 138.6 (C25), vol.129

, 25.6 (C4), 22.4 (C12), 21.7 (C29), 21.0 (C5), vol.19, p.547, 1036.

, Compound I-205a was obtained following general procedure V using compound I-186a (3567 mg, 18.75 mmol, 1 eq.), THF (150 mL), and DIBAL-H 1 M in heptane (20.62 mL, 20.62 mmol, 1.1 eq.). Workup and purification afforded I

, Rf = 0.43 (pentane:AcOEt 9:1) 1 H NMR (400 MHz, CDCl3): ? 6.11 (t, J = 3.6 Hz, 1H, H3), 4.13 (bs, 1H, H1), 2.32 (t, J = 7.2 Hz, 2H, H9), 2.09 (m,2H, H4), 1.88 (m, 1H, H6), 1.72 (m, 2H, H6', H5), 1.56 (m, 3H, H5', H10), 1.35 (m, 4H, H11, H12), vol.19

, 2 (C13) HRMS: FI+(eiFi) Caculated for, C9), 18.6 (C5, vol.14, p.913, 0990.

. I-205c, 2-(4-((tert-butyldimethylsilyl)oxy)but-1-yn-1-yl)cyclohex-2-en-1-ol

, Compound I-205c was obtained following general procedure V using compound I-186c (737.7 mg, 2.649 mmol, 1 eq.), THF (23 mL), and DIBAL-H 1 M in heptane (2.84 mL, 2.835 mmol, 1.1 eq.). Workup and purification afforded I

, Experimental Data

, 2H, H9), 2.06 (m, 3H, H4, H6), 1.88 (m, 1H, H6'), 1.67 (m, 2H, H6', H5), 1.57 (m, 1H, H5'), 0.90 (s, 9H, H13), 0.08 (s, 6H, H11) 13 C NMR (100 MHz, vol.19

, (C5), -5.0 (2C, C11) HRMS: (ESI)+ Calculated for, vol.836, p.668, 1106.

. I-205d, 2-(phenylethynyl)cyclohex-2-en-1-ol

, Compound I-205d was obtained following general procedure V using compound I-186d (565 mg, vol.2, p.879

, 17 mL, 3.167 mmol, 1.1 eq.). Work-up and purification afforded I-205d in 68% yield (1.96 mmol, 385.8 mg), toluene (25 mL), and DIBAL-H 1 M in heptane

. I-206a,

, See synthesis of I-202a

, 12 (s, 2H, H20), MHz, CDCl3): ? 6.06 (bs, 1H, H3), vol.5

. Hz, 3H, H13) 13 C NMR (100 MHz, CDCl3): ? 136.9 (C8), 136.7 (C17), 135.4 (C22), 134.0 (C7), vol.133

, 131.8 (C21), 128.1 (C3), 128.1 (C2), 73.4 (C20), 72.6 (C18), 71.8 (C1), vol.64, 0811.

. I-206b, 10-pentyl-3,4,5a, vol.6, pp.8-9

, m, 2H, H6', H5), 1.67-1.62 (m, 3H, H5', H10), 1.37 (bs, 4H, H11, H12), 0.92 (bs, 3H, H13) 13 C NMR (100 MHz, CDCl3): ? 139.4 (C8), 137.5 (C17), 133.0 (C7, vol.132, p.901, 1049.

. I-206c, 11-methyl-10-pentyl-3,4,5a,6,7,8-hexahydro-1H-isobenzofuro

, See synthesis of I-202c

, MHz, CDCl3): ? 6.02 (t, J = 4.0 Hz, 1H, H3), 5.09 (s, 2H, H18), vol.3

, 2 (C11), 30.6 (C10), 29.6 (C6), 29.2 (C9), 26.3 (C4), 22.6 (C12), vol.64, 1050.

, See synthesis of I-202d

, Rf = 0.59 (pentane:AcOEt 8:2) 1 H NMR (400 MHz, CDCl3): ? 7.41-7

1. Hz, 2H, H4), 2.07 (m, 1H, H6), 1.94-1.80 (m, 2H, H6', H5), 1.68 (m, 1H, H5'), 1.29 (m, 2H, H10), 1.08 (m, 4H, H11, H12), 0.73 (t, J = 6.8 Hz, 3H, H13) 13 C NMR (100 MHz, CDCl3): ? 140.1 (C23), 137.3 (C16), vol.7, p.703

. I-206e, 11-(4-nitrophenyl)-10-pentyl-3,4,5a, vol.6, pp.8-9

, AcOEt 8:2) 1 H NMR (400 MHz, CDCl3): ? 8.30 (d

. Hz, 2.47 (m, 1H, H9'), 2.29 (bs, 2H, H4), 2.06 (m, 1H, H6), 1.91-1.82 (m, 2H, H6', H5), 1.68 (m, 1H, H5'), 1.25 (m, 2H, H10), 1.08 (m, 4H, H11, H12)

, 31.8 (C11), vol.30

. Calculated-for, found : 420.2162 (Diff. : 1.78 ppm) IR: ? 2928, vol.856, p.731, 0906.

. I-206f, 11-(3-nitrophenyl)-10-pentyl-3,4,5a, vol.6, pp.8-9

, MHz, CDCl3): ? 8.24 (d, J = 7.2 Hz, 1H, H26), vol.8

. Hz, 1H, H1), 2.77 (m, 1H, H9), 2.48 (m, 1H, H9'), 2.28 (bs, 2H, H4), 2.06 (m, 1H, H6), 1.91-1.82 (m, 2H, H6', H5), 1.68 (m, 1H, H5'), 1.25 (m, 2H, H10), 1.07 (m, 4H, H11, H12), 0.73 (t, J = 6.8 Hz, 3H, H13) 13 C NMR (100 MHz, CDCl3): ? 148.5 (C25), 141.8 (C23), 137.0 (C21), 136.9 (C8), 135.6 (rotamer, C28), vol.135

, C13) HRMS: (ESI)+ Calculated for, ppm) IR: ? 2927, vol.13, p.734, 0811.

. I-206g, 11-(4-methoxyphenyl)-10-pentyl-3,4,5a, vol.6, pp.8-9

. Hz, 1H, H24'), 6.94 (d, J = 8.0 Hz, 2H, H23), 6.11 (bs, 1H, H3), 5.05, 5.04 (ABq, J = 13.9 Hz, 2H, H18

, = 6.8 Hz, 3H, H13) 13 C NMR (100 MHz, CDCl3): ? 158.8 (C26), 137.7 (C8), 137.5 (C21), 135.4 (C16), vol.134

, + : 405.2429, found : 405.2412 (Diff. : 2.85 ppm) IR: ? 2928, p.832, 0904.

. I-206h, 11-(3-methoxyphenyl)-10-pentyl-3,4,5a, vol.6, pp.8-9

1. Hz,

, ), 6.13 (bs, 1H, H3), 5.07, 5.03 (ABq, J = 13.5 Hz, 2H, H18

. Mhz, CDCl3): ? 159.7 (C25), 141.4 (C23), 137.2 (C8), 137.1 (C21), 135.5 (C22), vol.134

, 3 (rotamer, C24'), 113.0 (rotamer, C27), 112.8 (rotamer, C27'), 131.5 (C17), 129.7 (C26), 129.6 (C16), 128.3 (C3), 121.7 (rotamer, C28), 121.2 (rotamer, C28'), vol.114, 0905.

. I-206i, 10-pentyl-11-(thiophen-2-yl)-3,4,5a, vol.6, pp.8-9

, 3 (C20), 72.8 (C18), 132.6 (C2), 131.6 (C21), 130.7 (C16), 128.5 (C3), vol.127, p.696, 0904.

. I-206j,

, See synthesis of I-202j

, MHz, CDCl3): ? 7.21 (d, J = 6.8, 2H, H25), 7.11 (d, J = 6.8 Hz, 1H, H24), 7.05 (d, J = 6.8 Hz, 1H, H24'), vol.6

, = 6.8 Hz, 3H, H13) 13 C NMR (100 MHz, CDCl3): ? 137.5 (C22), 137.3 (C8), 137.0 (C23), vol.136

, 134.6 (C7), 132.9 (C2), 131.4 (C17), 129.5 (C16), 129.3 (2C, C25), vol.31, p.730, 1080.

. I-206k, 10-pentyl-11-(4-(trifluoromethyl)phenyl)-3,4,5a, vol.6, pp.8-9

, Rf = 0.90 (pentane:AcOEt 8:2) 1 H NMR (400 MHz, CDCl3): ? 7.69 (d, J = 7.7 Hz, 2H, H25), 7.38 (d, J = 7

, 1H, H1), 2.77 (m, 1H, H9), 2.48 (m, 1H, H9'), 2.28 (m, 2H, H4), 2.06 (m, 1H, H6), 1.93-1.80 (m, 2H, H6', H5), 1.68 (m, 1H, H5'), 1.26 (m, 2H, H10), 1.07

, 5 (C15), 31.8 (C11), 30.8 (C10), Hz, C27), 73.8 (C20), 72.7 (C18), vol.71, 1019.

, tert-butyl

, MHz, CDCl3): ? 6.13 (bs, 1H, H3), vol.5

, 11.9, 5.4 Hz, 1H, H9), 3.01 (ddd, J = 11.9, 11.9, 5.4 Hz, 1H, H9'), 2.61 (q, J = 7.4 Hz, 2H, H24), 2.28 (bs, 2H, H4), 2.01 (m, 1H, H6), 1.92-1.77 (m, 2H, H6', H5), 1.68 (m, 1H, H5), 1.15 (t, J = 7.6 Hz, 3H, H24), 0.90 (s, 9H, H13), 0.05 (s, 3H, H11), 0.04 (s, 3H, H11') 13 C NMR (100 MHz, CDCl3): ? 136, vol.9

, HRMS: (ESI)+ Calculated for, vol.836, p.776, 0938.

. I-206m, tert-butyldimethyl

, 2H, H10), 3.15 (m, 1H, H9), 2.89 (m, 1H, H9), 2.30 (bs, 2H, H4), 2.05 (m, 1H, H6), 1.95-1.80 (m, 2H, H6', H5), 1.70 (m, 1H, H5'), 0.77 (s, 9H, H13), -0.16 (s, 6H, H11) 13 C NMR (100 MHz

, 2C, C11) HRMS: (ESI)+ Calculated for [C29H39O3Si] + : 463.2668, found : 463.2675 (Diff. : -2.57 ppm) IR: ? 2928, vol.835, p.665, 0905.

. I-206n, , vol.10

, 1H, H1), 1.97 (m, 1H), 1.87 (m, 1H), 1.68 -1.54 (m, 3H), 1.41 (m, 1H) 13 C NMR, vol.12, p.698

. I-206o,

, See synthesis of I-202a

, pentane:AcOEt 8:2) 1 H NMR (400 MHz, CDCl3): ? 7

2. Hz,

3. Hz and J. H24)-;-t, 3H, H13) 13 C NMR (100 MHz, CDCl3): ? 142.4 (C28), 137.0 (C8), 136.6 (C17), 136.5 (C25), vol.135

, 24.1 (C23), 22.5 (C12), 21.5 (C29), 21.1 (C5), 15.0 (C24), vol.27, 1056.

. I-206p,

, See synthesis of I-202p

, pentane:AcOEt 8:2) 1 H NMR (400 MHz, CDCl3): ? 7.34 (m, 5H, H25, H31, H26), vol.7

. Hz, 1H, H24), 7.01 (d, J = 8.0 Hz , 2H, H27), 6.91 (d, J = 7.2Hz, 1H, H24'), vol.5

, = 15.7 Hz, 2H, H15), 2.68 (m, 1H, H9), 2.37 (m, 1H, H6), 2.31 (s, 3H, H29), 2.25 (m, 2H, H4), 2.17 (m, 1H, H9'), 1.90 (m, 2H, H6', H5), 1.80 (m, 1H, H5'), vol.1

, C11), 30.9 (C10), 30.8 (C6), 28.6 (C9, 135.6 (C23), 132.1 (C2), 131.8 (C16), 129.5 (C3), 129.1 (2C, C27), vol.128, p.558, 1032.

. I-206q, 10-pentyl-2-tosyl-1,2,3,4,5a, vol.6, p.8

2. Hz,

, C18), 33.0 (C9), 31.8 (C11), C21), 128.7 (C3), 127.6 (2C, C26), 122.5 (C22), 71.6 (C1), 64.7 (C15), 53.6 (C20, vol.51, p.548, 1064.

. I-206r,

. Hz,

3. Hz, H27'), 1.15 (t, J = 7.2 Hz, 3H, H24), 0.91 (bs, 3H, H13) 13 C NMR (100 MHz, CDCl3): ?, vol.171

, 129.6 (C3), 71.7 (C1), 64.8 (C15), 62.0 (2C, C26), 60.3 (C19), 39.6 (C18), vol.38, 1065.

. I-206s,

. Hz, 2H, H15), 2.92 (m, 1H, H9), 2.56 (m, 3H, H9', H23), 2.20 (m, 2H, H4), 1.89 (m, 1H, H5), 1.69 (m, 2H, H5', H6), 1.53 (m, 1H, H10), 1.44 (m, 1H, H6')

. Hz, 3H, H13) 13 C NMR (100 MHz, CDCl3): ? 172.2 (C25), 172.1 (C25'), 171.1 (C28), vol.170

, 4 (C3), 61.8 (C26), 61.8 (C26'), 61.5 (C29), 137.3 (C8), 137.0 (C21), 136.2 (C22), 135.3 (C2), 134.2 (C7), 129.7 (C16), vol.127

, C27') HRMS: (ESI)+ Calculated for, vol.14, p.633, 1066.

, Compounds I-206t was obtained following the general protocol VI using triyne I-201t (50 mg, p.107

, Rh(COD)Cl]2 (2.6 mg, 0.005 mmol, 5 mol%)

, Rf = 0.65 (pentane:AcOEt 8:2) 1 H NMR (400 MHz, CDCl3): ? 7.66 (d, J = 7.2 Hz, 2H, H26), vol.7

2. Hz, , vol.70

, 3 (C18), 42.2 (C20), 31.7 (C9), vol.62

, 3 (C5), 13.0 (C13) HRMS: (ESI)+ Calculated for, 21.5 (C12), 20.5 (C26), vol.18, p.548, 1070.

, Compounds I-206u was obtained following the general protocol VI using triyne I-201u (50 mg

, Experimental Data -Part I

, MHz, CDCl3): ? 6.20 (t, J = 4.0 Hz, 1H, H3), 5.01 (bs, 4H, H18, H20), 4.67 (s, 2H, H15), 4.09 (t, J = 6.0 Hz, 1H, H1), 8.92 (t, J = 7.6 Hz, 2H, H9), 2.20 (m, 2H, H4), 2.10 (m, 1H, H6), 1.78 (m, 2H, H6', H5), 1.64 (m, 2H, H5', H10), 1.34 (m, 5H, H10', H11, H12), 0.91 (m, 3H, H13) 13 C NMR (100 MHz, CDCl3): ? 159.0 (C8), 157.2 (C21), 138.0 (C16), 130.3 (C2), 129.4 (C3), vol.127, 0811.

, 987 mmol, 1 eq.uiv) in DCM (22.4 mL) at 0 °C was added NEt3 (3.00 mL, 21.57 mmol, 2.4 eq.) and tosyl chloride (1.75 g, 8.897 mmol, 1 eq.). The mixture was stirred at room temperature for 3 days then diluted with Et2O, washes with HCl 1 M, sat NaHCO3 and brine. The crude was dried over MgSO4 and concentrated in vacuo, vol.8

. I-208a, 2-(hept-1-yn-1-yl)cyclohex-2-en-1-yl acetate

, To a solution of 205a (1818 mg, 9.454 mmol, 1 eq.) and DMAP (117.1 mg, 0.945 mmol, 0.1 eq.) in dry

, 09 mL, 65.4 mmol, 6.92 eq.) and acetic anhydride (1.33 mL, 14.18 mmol, 1.5 eq.). The mixture was allowed to reach room temperature and stirred for 22 h. After this time, 1.5 eq. of acetic anhydride was added, and the mixture was stirred for 5 additional hours. The mixture was poured on water, extracted 3 times with Et2O and the organics were dried over MgSO4 and concentrated in vacuo. The crude was purifies by silica flash chromatography, DCM (18.2 mL) at 0 °C in a dry flask, was added freshly distilled Et3N

, MHz, CDCl3): ? 6.24 (t, J = 3.6 Hz, 1H, H3), vol.5, p.100

. Mhz, CDCl3): ? 170.7 (C14), 138.1 (C3), vol.120

, + : 235.1698, found : 235.1689 (Diff. : 0.21 ppm) IR: ? 2931, vol.668, 1236.

, To a solution of I-205a (100 mg, 0.52 mmol, 1 eq.) and pyridine (0.25 mL, 3.12 mmol, 6 eq.) in dry DCM (1.53 mL) at 0 °C was added methyl chloroformate

, DCM, dried over MgSO4 and concentrated in vacuo. Purification by silica flash chromatography (pentane:AcOEt 95:5) afforded I-208b as a white

, Rf = 0.76 (pentane:AcOEt 9:1) 1 H NMR (400 MHz, CDCl3): ? 6.24 (t, J = 3.6 Hz, 1H, H3), vol.5, p.100

. Mhz, CDCl3): ? 155.5 (C14), 138.2 (C3), 120.1 (C2), 89.5 (C8), 79.1 (C7), 73.1 (C1), vol.54

, + : 235.1698, found : 235.1689 (Diff. : 0.21 ppm) IR: ? 2931, vol.668, 1236.

, 3 eq.) in acetone (63 mL) were added diethyl malonate (1.90 mL, 12.59 mmol, 1 eq.) and propargyl bromide 80% in toluene (1.35 mL, 12.59 mmol, 1 eq.). The mixture was stirred at room temperature for one day. It was then washed with water and extracted twice with Et2O, dried over MgSO4 and concentrated in vacuo. Silica flash chromatography afforded I-209 as a clear oil with 47% yield in 75% purity

, MHz, CDCl3): ? 6.12 (t, J = 3.6 Hz, 1H, H3)

3. Hz and J. H17'-;-t, 3H, H13) 13 C NMR (100 MHz, CDCl3): ? 169.5 (C15), vol.168

. Calculated-for, found : 335.2214 (Diff. : 1.12 ppm) IR: ? 2932, 1030.

. I-212, 2-((4-chlorobut-2-yn-1-yl)oxy)tetrahydro-2H-pyran

, 566 mmol, 1 eq.) in DCM (25 mL) was added dihydropyran (1.35 mL, 14.35 mmol, 1.5 eq.) and PPTS (240.4 mg, 0.957 mmol, 0.1 eq.). The mixture was stirred at room temperature for 4h, then washed with brine and extracted 3 times with DCM. The organics were dried over MgSO4 and concentrated in vacuo. Purification by silica flash chromatography (pentane:AcOEt 9:1) afforded I-212 as a clear oil, vol.9

. I-213a, -bromobut-2-yn-1-yl)oxy)-1-(hept-1-yn-1-yl)cyclohex-1-ene, vol.6

, Propargyl bromide I-213a was obtained following general procedure VII using propargyl alcohol I-203a (770 mg, 2.957 mmol, 1 eq.), PPh3 (949.8 mg, 3.549 mmol, 1.2 eq.) and CBr4 (1176 mg, 3.549 mmol, 1.2 eq.) in dry DCM (17.4 mL). Work-up and purification (pentane:AcOEt 95:5) afforded the propargyl bromide I

, 96 (s, 2H, H18), 3.96 (bs, 1H, H1), 2.30 (t, J = 6, MHz, CDCl3): ? 6.17 (bs, 1H, H3), 4.40 (s, 2H, H15), vol.3

, 3 (C6), 26.0 (C4), 22.5 (C12), 19.6 (C9), C1), 57.5 (C15), 31.3 (C11), 28.8 (C10), vol.73, p.614, 1073.

. I-213f, diethyl 2-(4-bromobut-2-yn-1-yl)-2-(2-(hept-1-yn-1-yl)cyclohex-2-en-1-yl)malonate

, Compound I-213f was prepared following general procedure VII using propargyl alcohol I-203f, vol.291, p.9

, PPh3 (232.9 mg, 0.870 mmol, 1.2 eq.) and CBr4 (288.6 mg, 0.870 mmol, 1.2 eq.) in dry DCM (17.4 mL). Work-up and purification (pentane:AcOEt 9:1) afforded the propargyl bromide I

, Rf = 0.56 (pentane:AcOEt 9:1) 1 H NMR (400 MHz, CDCl3): ? 6.19 (bs, 1H, H3), 4.23 (m, 4H, H29), 3.91 (t, J = 2.0 Hz, 2H, H18), 3.32 (m, 1H, H1), 3.16 (dt, J = 17.3, 2.0 Hz, 1H, H15), 3.03 (dt, J = 17.3, 2.0 Hz, 1H, H15'), 2.21 (t, J = 7.2 Hz, 2H, H9), 2.08 (m, 2H, H4), 1.80 (m, 3H, H6, H5), 1.52 (m, 3H, H5', H10), 1.32 (m, 4H, H11, H12), 1.29 (t, J = 7.2 Hz, 6H, H30), 0.90 (t, J = 7.2 Hz, 3H, H13) 13 C NMR (100 MHz, CDCl3): ? 170.0 (C28), 169.5 (C28'), vol.138, 1040.

. I-214, 4-methyl-N-(pent-2-yn-1-yl)benzenesulfonamide

, mL) under argon was added Boc2O (572 mg, 2.570 mmol, 1.1 eq.), freshly distilled Et3N (0.325 mL, 2.336 mmol, 1 eq.), and DMAP (57 mg, 9.467 mmol, 0.2 eq.). The mixture was stirred at room temperature for 5 hours, then quenched with water, extracted 3 times with AcOEt, washed with brine and dried over MgSO4 then concentrated in vacuo, dry DCM

M. Charpenay, A. Boudhar, A. Siby, S. Schigand, G. Blond et al., Adv. Synth. Catal, vol.353, p.3151, 2011.

H. Lechuga-eduardo, M. Romero-ortega, and H. F. Olivo, European J. Org. Chem, p.51, 2016.

T. Yao, X. Zhang, and R. C. Larock, J. Am. Chem. Soc, vol.126, p.11164, 2004.

H. Liu, P. Yan, Y. Li, J. Liu, Q. Sun et al., Monatshefte für Chemie -Chem. Mon, vol.143, p.1055, 2012.

C. Praveen, P. Kiruthiga, and P. T. , Synlett, 1990.

N. Jeong, D. H. Kim, and J. H. Choi, Chem. Commun. (Camb), 1134.

J. S. Yadav, B. V. Reddy, and A. K. Mishra, Chem. Lett, p.280, 2010.

B. M. Trost and M. T. Rudd, J. Am. Chem. Soc, vol.127, p.4763, 2005.

B. M. Trost and C. A. Kalnmals, Org. Lett, 2017.

Y. Yin, W. Ma, Z. Chai, and G. Zhao, J. Org. Chem, p.5731, 2007.

K. Sugino, H. Yoshimura, T. Nishikawa, and M. Isobe, Biosci. Biotechnol. Biochem, 2008.

, Diamide II-135 (20 mg, 0.071 mmol, 1 eq) was dissolved in MeOH (3 mL) and m-CPBA was added

, The mixture was stirred at room temperature overnight, then an additional -CPBA was added. The mixture was then stirred for 48 hours, before being quenched with saturated NaHCO3 and extracted two times with DCM, then dried over MgSO4 and concentrated in vacuo. This crude was dissolved in DCM (2 mL) and TFA was added (0.5 mL). The mixture was stirred for 1 h, then quenched with saturated NaHCO3 and extracted two times with DCM, then dried over MgSO4 and concentrated in vacuo. Purification by silica flash chromatography

, Rf = 0.52 (AcOEt/MeOH 9/1) 1 H NMR (400 MHz, CDCl3): 8.39 (d, J = 7.6 Hz, 1H, H12), 7.49 (d, J = 7.2 Hz, 1H, H9), vol.7

C. Nmr, MHz, CDCl3): ? 167.9 (C14), 165.4 (C19), 135.1 (C13), vol.129

, (C6) HRMS: (ESI)+ Calculated for, vol.20

, 12(41H)-dione II-149 (49.3 mg, 0.113 mmol, 1 eq) was dissolved in CDCl3 (4.2 mL). The mixture was cooled to 0 °C then H2O2 30% in water (85 ?L, 2.55 mmol, 22.5 eq) was added dropwise, and the mixture was stirred for 1.5 hours. After this time, the stirring was stopped, and the mixture was allowed to settle. With a syringe, the organic bottom layer was taken and dried over Na2SO4 in an Erlenmeyer that had previously been cooled in ice

, Rf = / compound unstable on silica. 1 H NMR (500 MHz, CDCl3): ? 8.35 (d, J = 6.4 Hz, 1H, H12), vol.7, p.48

, J = 6.4 Hz, 1H, H9), 7.38 (ddd, J = 7.5, 6.4, 1.2 Hz, 1H, H10 or H11)

, indole-5-carboxylate II-195 (575 mg, 2.243 mmol, 1 eq) was dissolved in AcOH (5.26 mL) and NaBH3CN (423 mg, vol.6

, 12(41H)-concentrated in vacuo. Purification by silica flash chromatography

, Rf = 0.25 (AcOEt) 1 H NMR (500 MHz, CDCl3): ? 8.82 (d, J = 5.0 Hz, 1H, H5), vol.8

1. Hz,

, II-145. (13aR)-6a-hydroxy-6a1-methoxy, vol.13

, Diamide II-135 (40 mg, 0.143 mmol, 1 eq) was dissolved in MeOH (8 mL) and m-CPBA was added, p.9

, The mixture was stirred at room temperature for 7 hours before concentrated, dissolved in DCM, quenched with saturated NaHCO3 and extracted two times with DCM. The organics were dried over MgSO4 and concentrated in vacuo. Purification by silica flash chromatography (AcOEt:MeOH 10:0 to 93:7) afforded enamide II-145 as a yellow oil in 56% yield (26.3 mg, 0.080 mmol) and II-146 as a yellow

, MHz, CDCl3): ? 8.17 (dd, J = 8.0, 1.0 Hz, 1H, H12)

1. Hz, m, 1H, H20), 3.11 (t, J = 13.6 Hz, 1H, H5', vol.129, p.89

, C9), 121.74 (C10), 115.56 (C11), 93.26 (C2), 75.56 (C7), 62.67 (C3), 51.79 (C21, vol.39

. Ii-146, , vol.2, pp.13-16

, See synthesis of II-145

, AcOEt:MeOH 98:2) 1 H NMR (500 MHz, CDCl3): ? 8.40 (dd

, J =, vol.17, issue.5

1. Hz,

, 166.6 (C14), 136.0 (C13), 128.1 (C8), 127.7 (C2), vol.126

, mmol, 1 eq) was dissolved in hexafluoroisopropanol (3 mL) and m-CPBA was added (140.7 mg, 0.628 mmol, 8.8 eq). The mixture was stirred at room temperature overnight then quenched with saturated NaHCO3 and extracted two times with DCM, dried over MgSO4 and concentrated in vacuo. This crude was dissolved in DCM (2 mL) and TFA was added (0.5 mL). The mixture was stirred for 30 minutes, then quenched with saturated NaHCO3 and extracted two times with DCM

, Purification by silica flash chromatography (AcOEt:MeOH, vol.10, issue.2

H. Nmr, 500 MHz, CDCl3): ? 7.76 (dd, J = 7.8, 1.6 Hz, 1H, H9), 7.61 (td, J = 7.7, 1.7 Hz, 1H, H11), 7.54 (dd, J = 7.7, 1.6 Hz, 1H, H12), vol.7

C. Nmr, (C15), 30.1 (C18), 23.2 (C17). HRMS: (ESI)+ Calculated for, MHz, CDCl3): ? 200.5 (C7), 170.6 (C19), 170.4 (C2), 168.6 (C14), 134.8 (C8), 132.7 (C13), 132.2 (C11), 130.7 (C9), vol.128

, 12-((tert-butyldimethylsilyl)oxy)-1,2,41, vol.5

, The mixture was cooled to -78 °C then LiHMDS 1M in THF (0.25 mL, 0.250 mmol, 1 eq) was added. The mixture was stirred for 1.5 hours, then TBDMSCl (0.06 mL, 0.375 mmol, 1.5 eq) was added. The mixture was stirred an additional 1.5 hours before being diluted with AcOEt, washed with water, extracted with AcOEt 2 times dried over MgSO4 and concentrated in vacuo, a dry flash under argon was dissolved II-135 (70 mg, 0.250 mmol, 1 eq) in dry THF (5 mL)

. Rf-=-/-unstable-on and . Silica, Could not be isolated, Characteristic signals : 1 H NMR (500 MHz, CDCl3) : ? 7.81 (d, J = 8.1 Hz, 1H, H12)

, Experimental data -Part II

, 1 eq) was dissolved in dry THF (7.2 mL) in a dry flask under argon. The mixture was cooled to -78 °C then LiHMDS 1 M in THF (0.376 mL, 0.376 mmol, 1.05 eq) was added and the mixture was stirred 1 h. Then, a solution of phenylselenyl chloride, vol.1

, mL) was added in one go. The mixture was stirred for 1 hour then quenched with saturated NH4Cl, extracted twice with AcOEt, dried over MgSO4 and concentrated in vacuo. Purification by silica flash chromatography (AcOEt:MeOH 10:0 to 9:1) afforded II-149 and II-150 as a mixture of separable diastereomers (with Et2O:MeOH eluent system), dry THF

. Hz, 2H, H22), 7.44 (dd, J = 7.5, 1.0 Hz, 1H, H9), 7.40 -7.35 (m, 1H, H10), 7.33 (dt, J = 8.0, 1.0 Hz, 1H, H11)

1. Hz, Hz, 1H, H17), 2.46 (ddd, J = 18.6, 12.7, 6.8 Hz, 1H, H18'), 2.15 -1.96 (m, 1H, H16), 1.73 (qd, 5.5 Hz, 1H, H17'). 13 C NMR (101 MHz, CDCl3) : ? 168.2 (C14), 165.8 (C19), 135.5 (C22), 135.4 (C13), 131.0 (C8), 129.4 (C23), vol.12

, Experimental Data II-150. (41S,13S,13aS)-13-(phenylselanyl)-1,2,5, vol.6

, Et2O : MeOH 98 :2) 1 H NMR (500 MHz, CDCl3): ? 8.36 (d, J = 7.8 Hz, 1H, H12), 7.77 (dd, J = 7.5, 1.8 Hz, 2H, H22), 7.45 (d, J = 7.4 Hz, 1H, H9), 7.41 -7.28 (m, 5H, H13, H14, H23, H24), vol.5

. Ii-152a, dimethyl 3-allyl-3-formylhexanedioate II-133 (80 mg, 0.396 mmol, 1eq) was dissolved in chloroform (2 mL) in dry ?-wave tube under argon. Activated molecular sieves and pyrrolidine, p.1

, 54 (s, 1H, H9), MHz, CDCl3): ? 9, vol.173

, HRMS: (ESI)+ Calculated for, C12), 51.8 (2C, C1, C8), 50.1 (C4), vol.119

, 1 eq) was dissolved dry toluene (1.1 mL) in a dry flask under argon, the diallylamine (43 ?L, 0.346 mmol, 1 eq

, Purification by silica flash chromatography (pentane:AcOEt 7:3 to 0:10) afforded 3 fractions. The least polar fraction contained a mixture of II-152a (clear oil) and II-154, the second fraction contained II-156 (yellowish oil) and the most polar fraction contained II-155, H NMR analysis showed II

, :3) Obtained in a mixture with II-152a

C. Mhz,

, Rf = 0.51 (AcOEt) 1 H NMR (500 MHz, CDCl3): ? 5.92 (s, 1H, H9), vol.5

2. Hz, , vol.2

, Experimental Data II-156. methyl (E)-2-(6-oxo-1-(prop-1-en-1-yl)-1,4,5,6-tetrahydropyridin-3-yl)acetate See synthesis of II-154

, Rf = 0.60 (AcOEt) 1 H NMR (500 MHz, CDCl3): ? 7.00 (dd, J = 14.5, 1.9 Hz, 1H, H10), vol.6

, mmol, 1 eq) was dissolved in toluene (10 mL) and allyl alcohol (3 mL), and CSA (23.0 mg, 0.099 mmol, 0.1 eq) was added. The flask was fitted with a Dean-Stark apparatus under argon, which's finger had previously been filled with activated molecular sieves and toluene. The glassware was calorifugated with cotton and aluminium foil and the mixture was refluxed for 20 hours. xylene (10 mL), fitted with the Dean-Stark apparatus, now filled with molecular sieves and xylene. The mixture was refluxed in calorifugated glassware for 20 hours

, Rf = 0.63 (pentane:AcOEt 9:1) 1 H NMR (500 MHz, CDCl3): ? 9.55 (s, 1H, H13), 6.01 -5.81 (m, 2H, H2, H11), 5.78 -5.50 (m, 1H, H15), 5.37 -5.20 (m, 4H, H1, H12), 5.17 -5.05 (m, 2H, H16, vol.131

, 131.5 (C15), 120.0 (C16), vol.118

, Experimental data -Part II

, II-158. allyl 3-(3-allyl-2-(allyloxy)-5-oxotetrahydrofuran-3-yl)propanoate

, II-158 was obtained as a byproduct during several Claisen allylations using similar conditions as those described for the synthesis of II-157 (clear oil, max yield 22%)

, Rf = 0.48 (pentane : AcOEt 9:1) 1 H NMR (500 MHz, CDCl3): ? 5.97 -5.80 (m, 2H, H2, H12), 5.79 -5.61 (m, 1H, H15)

=. Rf, 19 (pentane:AcOEt 5:5) II-157 (103 mg, 0.350 mmol, 1 eq) was dissolved in degassed DCE, p.12

, 385 mmol, 1.1 eq) and AcOH (22 ?L, 0.385 mmol, 1.1 eq) were added. The mixture was stirred at room temperature for 5 hours, then heated in an oil bath overnight. It was then washed with saturated NaHCO3, extracted 3 times with DCM, dried over MgSO4 and concentrated in vacuo. Purification by silica flash chromatography, a dry ?-wave tube under argon, then tryptamine (62.9 mg, 0

, Inseparable mixture of diastereomers, Characteristic signals assigned by comparison with methyl ester analog 1 H NMR (500 MHz, CDCl3): ? 8.16 (s, 1H, H1), 6.15 (m, 1H, H24)

, Experimental Data II-160-trans. allyl 3-((1S,11bR)-1-allyl-3-oxo-2,3,5,6,11,11b-hexahydro-1H-indolizino

, Characteristic signals assigned by comparison with methyl ester analog 1 H NMR (500 MHz, CDCl3): ? 8.93 (s, 1H, H1), 5.92 (ddt, Rf = 0.19 (pentane:AcOEt 5:5) Inseparable mixture of diastereomers

, 1H-indol-3-yl)ethyl)imino)methyl)-3-allylhexanedioate II-157 (50 mg, 0.170 mmol, 1 eq) was dissolved in degassed DCE (2 mL) in a dry ?-wave tube under argon, then tryptamine (29.9 mg, 0.187 mmol, 1.1 eq) was added. The mixture was stirred at room temperature for 5 hours, then heated in an oil bath overnight. It was then washed with water

, 99 (s, 1H, H27), 6.01 -5.77 (m, 2H, H2, H11), 5.58 (dq, pentane:AcOEt 5:5) 1 H NMR (500 MHz, CDCl3): ? 8.05 (bs, 1H, H26), 7.62 (d, J = 7.8 Hz, 1H, H21), 7.35 (s, 1H, H16), 7.32 (d, J = 8.1 Hz, 1H, H24), 7.18 (t, J = 8.1 Hz, 1H, H23), 7.11 (t, J = 7.8 Hz, 1H, H22), vol.6

, Experimental data -Part II

. Ii-163, -(1H-indol-3-yl)ethyl)-3-allyl-2-(allyloxy)-5-oxopyrrolidin-3-yl)propanoate, vol.3

, pentane:AcOEt 5:5) 1 H NMR (500 MHz, CDCl3): ? 8.29 (bs, 1H, H26), 7.83 (d, J = 7.9 Hz, 1H, H21), 7.57 (d, J = 8.1 Hz, 1H, H24), vol.7

. Hz, 2H, H18), 2.55, 2.29 (ABq, J = 16.7 Hz, 2H, H8), 2.53 -2.45 (m, 2H, H5), 2.20 -1.95 (m, 4H, H14, H6). 13 C NMR (101 MHz, CDCl3) : ? 173.7 (C9), vol.172

, 3 (C24), vol.112

, 6615 mmol, 1 eq) was dissolved in toluene (6.6 mL) and allyl alcohol (2.1 mL) and CSA (30.7 mg, 0.132 mmol, 0.2 eq). The flask was fitted with a Dean-Stark apparatus under argon

, 6 mL), fitted with the Dean-Stark apparatus, now filled with molecular sieves and xylene. The mixture was heated in a bath at 140 °C in calorifugated glassware for 24 hours

, MHz, CDCl3): ? 9.46 (s, 1H, H15), 5.99 -5.83 (m, 2H, H2, H13), 5.73 -5.57 (m, 1H, H17), 5.34 -5.19 (m, 4H, H1, H14), 5.16 -5.05 (m, 2H, H18), 4.57 (m, 4H, H3, H12), 2.37 -2.33 (m, 2H, H7), 2.32 -2.22 (m, 4H, H10, H16), 1.92 -1.84 (m, 2H, H9), 1.57 -1.49 (m, 4H, H6, H5). 13 C NMR (101 MHz, CDCl3): ? 205.0 (C15)

, mL) in a dry ?-wave tube under argon, then tryptamine (49.7 mg, 0.310 mmol, 2 eq) and TFA (12 ?L, 0.171 mmol, 1.1 eq) were added. The mixture was ?-waved 3 times for 1.5 hours. It was then washed with saturated NaHCO3, extracted 3 times with DCM, dried over MgSO4 and concentrated in vacuo. Purification by silica flash chromatography (pentane:AcOEt 5:5 to 0:10) afforded II-160-cis (31.3 mg, 0.077 mmol) and II-160-trans (31.3 mg, 0.077 mmol) as light yellow foams. Note: on bigger scales

, Rf = 0.53 (AcOEt) 1 H NMR (500 MHz, CDCl3): ? 8.69 (bs, 1H, H1), vol.7

1. Hz, , vol.7

1. Hz, 1H, H26), 5.56 -5.44 (m, 2H, H22), 5.41 -5.28 (m, 2H, H27), vol.5

, HRMS: (ESI)+ Calculated for, 21.1 (C6), vol.18

, Rf = 0.22 (AcOEt) 1 H NMR (500 MHz, CDCl3): ? 10.33 (s, 1H, H1), 7.66 (dd, J = 7.2, 7.2 Hz, 2H, H9, H12), 7.34 (t, J = 7.2 Hz, 2H, H11), 7.26 (t, J = 7.2 Hz, 1H, H10), vol.6

, C9), 112.5 (C7), 111.4 (C12), 66.0 (C25), vol.118

, eq) and P(OPh)3 (76 ?L, 0.284 mmol, 0.04 eq) in THF (5 mL), prepared in a Schlenk glassware under an argon atmosphere, was introduced under argon into a stainless steel autoclave containing the substrate II-167 (2.02g, 7.096 mmol, 1 eq) in THF (67 mL). The reactor was purged three times with H2/CO (1:1, 10 bar) and filled with H2/CO (1:1, 20 vented to ambient pressure. The reaction mixture was evaporated

, MHz, CDCl3): ? 9.59 (d, J = 2.4 Hz, 1H, H13)

, HRMS: (ESI)+ Calculated for

, MHz, CDCl3): ? 8.11 (s, 1H, H1), 7.47 (dt, J = 7.9, 1.0 Hz, 1H, H3), vol.7

1. Hz, 13 C NMR (101 MHz, CDCl3): ? 136.7 (C7), vol.126

, 3 (C3), 113.6 (C8), 111.6 (C6), Hz, C16), 123.6 (C5), vol.119

, Experimental data -Part II

, 1 eq) was dissolved in dry THF (2.5 mL) in a dry flask under argon. The mixture was cooled to -78 °C then LiHMDS 1 M in THF (0.256 mL, 0.256 mmol, 2.1 eq) was added and the mixture was stirred 1.5. Then, a solution of phenylselenyl chloride (26.8 mg, 0.134 mmol, 1.1 eq) in dry THF (0.30 mL) was added in one go. The mixture was stirred for 2 hours then quenched with saturated NH4Cl, extracted twice with AcOEt, dried over MgSO4 and concentrated in vacuo. Purification by silica flash chromatography

, Rf = 0.28 (pentane:AcOEt 5:5) 1 H NMR (500 MHz, CDCl3): ? 9

. Hz, 1H, H11), 7.11 (t, J = 7.8 Hz, 1H, H10), 5.89 (ddt, J = 16.6, 11.1, 5.7 Hz, 1H, H26), 5.58 (m, 1H, H16), 5.41 -5.24 (m, 2H, H27), 5.19

C. Nmr, 3 (2C, C30), 129.2 (2C, C31), 127.1 (C28), 126.1 (C8), 121.8 (C11), MHz, CDCl3): ? 174.7 (C24), 169.8(C3), 136.8 (C13), 136.1 (C29), 132.6 (C16), 131.3 (C26), 129.8 (C2), vol.129

, Experimental Data

, Rf = 0.23 (pentane:AcOEt 5:5) The minor diastereomer was obtained in a mixture with the major diastereomer. Characteristic signals : 1 H NMR (500 MHz, CDCl3): ? 9

3. Hz and . H22, HRMS: (ESI)+ Calculated for

, 7S)-16-hydroxy-6, vol.10, pp.14-20

, mL) at -78 °C and ozone was bubbled in the media for 1h. Then dimethylsulfide (6.6 ?L, 0.089 mmol, 1 eq) was added and the mixture was allowed to reach rt and stirred overnight. The mixture was concentrated in vacuo and purification by silica flash chromatography, II-173-cis a and b (50 mg, 0.089 mmol, 1 eq) was dissolved in DCM:MeOH, vol.1

, Rf = 0.29 (AcOEt:MeOH 9:1) Mixture of diastereomers in 1:0.5 ratio, each of which show aldehyde-enol tautomeric equilibrium depending on the solvent. 1 H NMR (400 MHz, MeOD-d4): ? 7.87 -7.71 (m, 1H, H25 of tautomer 1), 7.53 (d, J = 8.7 Hz, 1H, H9 or H12), 7.47 -7.35 (m, 2H, H9 or H12, H10 or H11), 7.28 (t, J = 6.6 Hz, 1H, H10 or H11), 6.99 -6.85 (m, 1H, H18)

, C9 or C10 or C11 or C12), vol.174

, 2 (C22), 128.4 (C9 or C10 or c11 or C12), vol.129

, C24), 47.2 (C19), 45.2 (C5), 44.6 (C6), vol.40

, S,8a'R)-8'-allyl-2,5'-dioxo-2',3',6',7',8',8a'-hexahydro-5'H-spiro

, To a solution of II-165-trans (50 mg, 0.123 mmol, 1 eq) in dry acetonitrile:dry ethylene glycol, vol.1, pp.1-1

, 3 mg, 0.492 mmol, 4 eq) at room temperature. The mixture was then warmed to 40 °C and stirred for 3 hours. It was then quenched with cold saturated NaHCO3 and extracted 3 times with DCM, dried over MgSO4 and concentrated in vacuo. Purification by silica flash chromatography (pentane:AcOEt 5:5 to 0:10) afforded II-180 as a yellow oil in 7% yield (3.8 mg, 0.009 mmol) and II-181 as a yellow, mL) under argon was added PIFA (58.2 mg, 0.135 mmol, 1.1 eq) and ammonium chloride, vol.26

, pentane:AcOEt 3:7) 1 H NMR (500 MHz, CDCl3): ? 7.60 (dd, J = 7.7, 1.0 Hz, 1H, H12), vol.7, p.49

, J = 7.5, 1.2 Hz, 1H, H9), 7.42 (td, J = 7.7, 1.2 Hz, 1H, H11), 7.31 (td, J = 7.5, 1.0 Hz, 1H, H10), 5.97 -5.77 (m, 2H, H18, H26), vol.121

, Experimental Data II-181. allyl 4-(1-allyl-7a-(2-hydroxyethoxy)-4-oxo-1,2,3,4,7a, vol.2, p.3

, MHz, CDCl3): ? 9.36 (s, 1H, H1), 8.41 (d, J = 5.2 Hz, 1H, H5), 8.10 (dd, J = 7.9, 1.1 Hz, 1H, H9), 7.86 (d, J = 5.2 Hz, 1H, H6), 7.65 -7.44 (m, 2H, H12, H11), 7.32 -7.26 (m, 1H, H10), 5.90 -5.67 (m, 2H, H26, H16), vol.137

, 1 (C15), 29.4 (C14), 19.3 (C16), vol.35

, mmol, 1 eq) in acetone (0.63 mL) was added NBS (56.6 mg, 0.317 mmol, 1.3 eq). The mixture was stirred at room temperature for 3.5 hours and concentrated in vacuo. Purification by silica flash chromatography (pentane:AcOEt 7:3) afforded II-183 as a yellow oil in 68% yield

, Experimental data -Part II

, MHz, CDCl3): ? 10.11 (s, 1H, H1), 7.56 -7.50 (m, 2H, H9, H12), 7.26 -7.21 (m, 1H, H10), vol.7

, 118.8 (C27), 118.7 (C9), 118.7 (C22), vol.113

, HRMS: (ESI)+ Calculated for

, II-184. (1S,7aR,12bR)-1-allyl-1-(4-(allyloxy)-4-oxobutyl

, 9 mL) in a dry flask under argon, then recrystallized benzoyl peroxide (87.4 mg, 0.270 mmol, 1.1 eq) was added and the mixture was stirred at room temperature. The reaction was monitored by TLC and benzoyl peroxide was added when the reaction did not advance (final quantity: 8.8 eq)

, pentane:AcOEt 5:5) 1 H NMR (500 MHz, CDCl3): ? 8.05 -7.96 (m, 2H, H30), 7.69 -7.56 (m, 2H, H12, H32), 7.46 (t, J = 7.8 Hz, 2H, H31), 7.44 -7.36 (m, 2H, H11, H9), 7.21 (td, J = 7.5, 1.0 Hz, 1H, H10), 6.05 -5.64 (m, 2H, H26, H16), 5.31 -5.17 (m, 2H, H27), vol.5

(. C18), HRMS : (ESI)+ Calculated for

, mmol, 1 eq) in acetone:water 10:1 (1.3 mL) was added 2,6-lutidine (57 ?L, 0.492 mmol, 4 eq), NMO (28.8 mg, 0.246 mmol, 2 eq) and K2

, 5 mol%) sequentially. The mixture was stirred at room temperature for 2 hours, then quenched with Na2S2O3 and extracted 3 times with DCM, dried over MgSO4 and concentrated in vacuo

, AcOEt:MeOH 10:0 to 8:2) afforded II-186 as a light foam in 33% yield (19.2 mg, 0.040 mmol) and II-187 as a light

, AcOEt:MeOH, vol.9, issue.1

1. Hz, , vol.7

1. Hz, H17'), 1.55 (dt, J = 13.9, 5.1 Hz, 1H, H15'), 1.44 -1.22 (m, 3H, H18, H19), 0.80 -0.65 (m, 1H, H19'). NH and OH exchangeable. 13 C NMR (101 MHz, vol.137

, 3 (C26), C13), 122.8 (C11), 120.3 (C10), 118.9 (C9), 113.2 (C7), 112.4 (C12, vol.132

, See synthesis of II-186

=. Rf, AcOEt:MeOH 3:7) This compound was obtained in a mixture, Characteristic signals: 1 H NMR, vol.46

. Mhz, CDCl3): ? 8.26 (s, 1H, H1), 7.51 (d, J = 6.1 Hz, 1H, H9 or H12), 7.35 (m, 1H, H9 or H12), 7.23 -7.17 (m, 1H, H10 or H11), vol.7

, mL) and NaIO4 (19.8 mg, 0.093 mmol, 2 eq) was added. The mixture was stirred at room temperature for 2 hours then quenched with Na2S2O3, extracted 3 times with DCM and concentrated in vacuo. Purification by silica flash chromatography

, Rf = 0.28 (acetone) 1 H NMR (400 MHz, DMSO-d6): ? 7.44 (d, J = 8.0 Hz, 1H, H12), 7.23 (d, J = 7.4 Hz, 1H, H9), 6.93 (ddd, J = 8.0, 7.4, 1.4 Hz, 1H, H11), vol.6

. Hz, 1H, H19'). 13 C NMR (101 MHz, DMSO-d6): ? 173.3 (C23), 169.0 (C3), 138.4 (C13), 133.0 (C2), vol.127

, HRMS: (ESI)+ Calculated for, 20.5 (C6), 18.5 (C18)

, 88 mL) and water (1 mL) was added a solution of II-173-cis (50 mg, 0.089 mmol, 1 eq) in THF (0.1 mL) at 0 °C

, Rf = 0.60 (AcOEt:MeOH 9:1) 1 H NMR (500 MHz, CDCl3): ? 7.97 (s, 1H, H1), 7.52 (d, J = 7.7 Hz, 1H, H9), 7.38 (td, J = 8.1, 0.9 Hz, 1H, H12), 7.23 -7.19 (m, 1H, H11), vol.7

, 114.1 (C7), 111.1 (C12), 65.5 (C25), 60.8 (C21), 40.9 (C5), vol.40

, HRMS: (ESI)+ Calculated for, vol.28

, 3 mL) in a dry shlenk under argon, then tryptamine (65.6 mg, 0.409 mmol, 1eq) was added. The mixture was refluxed for 1 hour, allowed to cool to room temperature and AcOH (0.02 mL, 0.409 mmol, 1 eq) was added. The flask was sealed and stirred at 130 °C overnight. The mixture was washed with NaHCO3, extracted 3 times with DCM and concentrated in vacuo. Purification by silica flash chromatography afforded II-191-trans in 33% yield (48.2 mg, 0.136 mmol) and II-191

, Et2O:MeOH 98:2) 1 H NMR (500 MHz, CDCl3): ? 7.99 (s, 1H, H1), 7.58 -7.46 (m, 1H, H9), 7.36 (dt, J = 8.1, 1.0 Hz, 1H, H12), 7.20 (ddd, J = 8.1, 7.0, 1.3 Hz, 1H, H11), vol.7

, 3 (C16), vol.29

, Experimental Data II-191-cis. methyl 3-((1S,12bR)-1-ethyl-4-oxo, vol.2, p.3

, Et2O:MeOH 98:2) 1 H NMR (500 MHz, CDCl3): ? 9

1. Hz,

C. Nmr, MHz, CDCl3) ? 175.6 (C22), 169.9 (C3), 136.5 (C13), vol.130

, HRMS: (ESI)+ Calculated for, C15), 24.1 (C19), 21.2 (C6), 7.0 (C18), vol.26

, (8'-ethyl-2,5'-dioxo-2',3',6',7',8',8a'-hexahydro-5'H-spiro

, Column chromatography afforded two fractions. The least polar fraction contained II-192-trans-trans and II-192-trans-cis, and the most polar contained II-192-cis-trans and

, 200 mg, 0.566 mmol, 1 eq) was dissolved in THF:water 1/1 (4 mL) at 0 °C and AcOH (32 ?L, 0.566 mmol, 1 eq) was added

, Rf = 0.30 (Et2O) 1 H NMR (500 MHz, CDCl3): ? 7.62 (dt, J = 7.7, 1.1 Hz, 1H, H12), vol.7

, C9), 122.2 (C12), 63.7 (C7), 62.0 (C21), 51.7 (C23), 41.5 (C6), 40.7 (C5), vol.122

, Rf = 0.24 (Et2O) 1 H NMR (500 MHz, CDCl3): ? 7.60 (dt, J = 7.7, 0.8 Hz, 1H, H12), vol.7

L. Salacz, C. Charpentier, J. Suffert, and N. Girard, J. Org. Chem, p.2257, 2017.

M. E. Kuehne, D. M. Rol, and R. Hafter, J. Org. Chem, p.3705, 1978.

R. Okabayashi, Y. Ohta, and T. Yokozawa, Macromolecules, vol.50, p.9589, 2017.

F. Wesche, H. Adihou, A. Kaiser, M. Wurglics, M. Schubert-zsilavecz et al., J. Med. Chem, p.3930, 2018.

M. E. Kuehne, J. Am. Chem. Soc, 1964.

M. Kaplan, J. Harley-mason, and L. Castedo, Chem. Commun, p.1444, 1969.

B. Flatt, R. Martin, T. Wang, P. Mahaney, B. Murphy et al., Experimental Data PUBLICATIONS Salacz, vol.335, 2009.

N. Girard, Desymmetrizing Hydroformylation of Dihydromuconic Acid Diesters: Application to the Synthesis of

&. J. Vindeburnol, . Org, and . Chem, , p.2257, 2017.

L. Salacz, N. Girard, J. Suffert, and G. Blond, * 'Carbonylative cycloaddition for the synthesis of medium-sized carbocycles, Monatsch. Chem, p.671, 2018.

L. Salacz, N. Girard, G. Blond, and J. Suffert, Synthesis of Polyheterocyclic Tropones by

, Org. Lett, p.3915, 2018.