Rendimiento Académico

T rib u ty ltin h y d rid e , 2 -m e th y l- 3 -b u ty n -2 -o l, 3 ,3 -d im e th y l-1 - butyne and 1 7a-ethynylestradiol were ai! com m ercial grade m aterials o b ta in e d from the A ld rich C hem ical C om pany, and 2 -m e th y l-2 - (trim e th y ls ily lo x y )-3 -b u ty n e was o b ta in e d by the s ily la tio n of the alcohol with trim ethylsilyl im idazole according to Chen

All NMR spectra were recorded on a Varian VXR-400 spectrom eter (400 MHz) on solutions in CDCI3 or de-benzene (CeDe) and the chemical shifts (Ô) were m easured in patrs per m illion (p.p.m ) The follow ing abbreviations are used in signal assignm ents; s (singlet), d (doublet), t (triplet), m (multiplet) and dd (doublet of doublets). and NMR spectra were recorded at 100.58 MHz and 74.6 MHz respectively on the Varian VXR-400 spectrom eter. Com mercially available M erck Kieselgel 60 F254 plates was used for analytical thin layer chrom a to g ra p h y (t.I.c.). They were visualised with ultra violet light or iodine. Column chrom atography were perform ed using Merck flash silica gel (200-400 mesh) stationary phase and hpIc was perform ed on a 5pm silica gel column with ethyl acetate-n-hexane as the mobile phase. All reactions were carried out under inert conditions using dry argon or nitrogen. All glassware for the reactions were dried in an oven at 130°C for at least 24 hours. Tem peratures below 0°C were obtained by cooling acetone with solid carbon dioxide (Cardice).

General Method for Hvdrostannation with Bu^SnH

Toluene (25cm3) was heated up to 80°C in a therm ostated oil bath and the alkyne was added. When the tem perature was steady at 80°C, trib utyltin hydride (BugSnH) and AIBN were added. The m ixture was then heated under an inert atm osphere for 3 hours, after which the tolu e n e was rem oved in vacuo. The resulting co lo u rle ss oil was

d is tille d in vacuo and the iso m e rs se p a ra te d by fla sh colum n chrom atography using n-hexane-ethylacetate (6.5 : 3.5 v/v) as eluent, or by hpic.

3 . 3 . 1 . P r e p a r a t i o n of E / Z - 4 - t r l b u t y l s t a n n y l - 2 - m e t h y l - 3

b u t e n -2 - o l

This was synthesised as an oil, giving a 4:1 ratio of Z- and E- isom ers, using the above m ethod and the follow ing m ole ratio of re a c ta n ts :

B ugS nH (1.7 g, 5.8 mmol, 1.57 ml), 2-m e th yl-3-b u tyn -2 -o l (1.34 g, 15.95 mmol, 1.55 ml) and AIBN (27 mg, 0.164 mmol).

Yield 4.57 g, 78%; B.p. 84 - 8 6°C (0.03 mmHg), [Lit2. 90 - 94°C (0.1 mmHg)];

IR (neat) 3330 (OH, st), 1620 (C=C, st) cm -i-

ÔH (C D C l3);1.00 - 0.80 (9 H, m; CH3); 1.75 - 1.25 (25H, m); Z - i s o m e r Found: C, 54.35; H, 9.62. Caic. fo r: C iy H3 6 0Sn; C, 54.43; H, 9.67% ÔH 5.75 (1H, d, 3Jh 13.4 Hz, 136.6 Hz, 3 jll9 s n 143.1 Hz; H-3); 6.58 (1H, d, 3Jh 13.4 Hz, 2 jll7 g ^ 65.5 Hz, 2 jll9 s n 68.6 Hz; H-4). 5c (C D C I3). 9.45 306.0 Hz, 343.5 Hz; Ca); 13.76 (05); 27.27 (3Jsn 53.4 Hz; C-y); 29.09 (2Jsn 20.4 Hz; C-p); 29.49 (0-1); 72.44 (3Jsn 57.40 Hz; 0-2); 124.90 (IJ^^^Sn 393.2 Hz, 411.3 Hz; 0-3); 152.0 (0-4).

E - i s o m e r 5h 6.07 (1H, d, 3Jh 19.2 Hz. 75.2 Hz, 2 jll9 $ n 78.5 Hz; H-4); 6.14 (1H, d, 3 j 19.2 Hz, 3 j i i 7 g „ 68.6 Hz, 3 jii9 s n 71.8 Hz; H-3). 5c 9.45 328.3 Hz, J i i9g „ 343.6 Hz; C-a); 13.75 (C-Ô); 27.27 ( 3 j l l 7 / l l 9 g „ 53.4 Hz; C-Y); 29.09 (2J117/Il9gn 20.4 Hz; G-P); 29.48 (0-1); 72.49 (3Jsn 57.4 Hz; 0-2); 122.44 ( Ij1 l7 g ^ 358.2 Hz; I j l l 9 g ^ 377.9 Hz; 0-4) 155.56 (0-3). S ll9 g n -4 0 .5 6 3 . 3 . 2 . P r e p a r a t i o n of ( E ) - 4 - T r l b u t y l s t a n n y l - 2 , 2 - d l m e t h y i - 4 - b u t e n e

Again this com pound was synthesised as an oil by the general m ethod using the following mole ratio of reactants.

BusS nH (1.77 g, 6.09 mmol); 3,3-dim ethyl-1-butyne (0.4 g, 6.09 mmol) and AIBN (0.61 mmol).

Yield: 2.04 g, (90%) B.p. 94 - 97°0/0.08 mmHg.

Found: 0 , 57.41; H, 10.66.

Calc, for: O igH sgSn: 0 , 57.93, H, 10.26% IR. (neat) 1618 (0 = 0 )c m -i

5h (ODOI3); 0.8 - 1.83 (36 H, m), 5.75 (1H, d, 3Jh 19.4 Hz, 2 jll7 g n

67.4 Hz, 2j119gn 70.6 Hz; H-4); 5.70 (1H, d, 3Jh 19.4 H z , 3 j l 1 7 g „ 75.6

Hz, 3 jll9 g n 79.2 Hz; H-3).

29.60 (2J117/Il9sn 20.5 Hz; C-p); 27.20 (2j i l 7/ i i9g^ 32.6 Hz; C -Y); 119.64 ( l j l l 7 g ^ 396.3 Hz, 1 j1 l9 $ n 404.3 Hz; C-4); 35.93 (3j l l 7/ i i9gn 55.1 Hz; 0 -2 ); 159.95 (C-3).

3 . 3 . 3 P r e p a r a t i o n of ( E ) - 4 - t r l b u t y i s t a n n y l - 2 - m e t h y l - 2

- ( t r i m e t h y l s i l y l o x y ) - 4 - b u t e n e

Again the reaction was carried out as detailed above, and the product obtained as an oil, with the following mole ratio of reactants:

B u s S n H (0.46 g, 1.59 mmol) AIBN (0.159 mmol) and 2-m ethyl-2- (trim e th ylsilylo xy)-3 -b u tyn e (0.1 g; 1.59 mmol)

Yield: 0.263 g (100%)

Found: C, 53.65; H, 9.91

Required for:, for C2oH4 4 0SiSn, C, 53.70; H, 9.91%

8h (CDCI3); 0.03 (9H, s, Si-(CH3)3); 0.8 - 1.91 (33H, m,); 6.09 (1H, d, 3Jh 19.4 Hz, 3 jil7 g n 77,5 Hz, 3 j i l 9 g „ 81.1 Hz; H-3); 5.95 (1H, d, 3 jy 19.4 H z ,2 jll7 g n 70.1, 2j l l 9gn 73.4 Hz; H-4).

8c (CDCI3); 2.34 (SI-CH3), 9.26 ( I j l l 7 g ^ 334.5 Hz, 350.0 Hz; C -a);1 3 .8 5 (C-8); 27.26 ( 3 jil7 / ll9 g n 55.6 Hz; C-y); 29.09(2 J1 1 7 /Il9 g n 23.7 Hz; C-p); 30.00 (C-1); 75.30 (2J117/Il9gn 50.6 Hz;); 122.40 ( i j l l 7 g n 338.1 Hz; i j n ^ s n 353.8 Hz; C-4); 157.83 (C-3).

3 . 3 . 4 . P r e p a r a t i o n of ( Z ) - 4 - t r i b u t y l s t a n n y l - 4 - o c t e n e , 2 , 7 - d i m e t h y l - 5 - o c t y n e - 2 , 7 - d l o l

The reaction was carried out by the same procedure as above in the follow ing mole ratios. The product was obtained as a solid and

re crysta llise d from ethanol:

BuaSnH (0.876 g, 3.0 mol), diyne (0.5 g, 3.00 mmol) and AIBN (0.003 m m oles). Yield, 1.17 g, 85%; M.p. 135 - 140°C Found: C 56.90, H, 9.01 ; Calc, for: C22H420Sn: C, 57.79, H, 9.29% ÔH (CDCI3) 0.88 - 1.55 (40H, m); 1.83 (2H, s, 2xOH); 6.28 (1H, s, 3 jll7 s n 1 1 1 .9 Hz, 3j119sn 117.08 Hz; H-3). ÔC (CDCI3) 11.70 ( lJ ll7 g n 326.6 Hz; C-a); 29.19 ( 3 jl 1 7 / 1 1 19.0 Hz; 0 -y); 30.08 (0-1); 31.31 (0-8); 65.57 (0-7); 75.47 ( J 1 1 7 / 1 1 9 2 0.I Hz; 0-2); 82.18 (0-5); 95.59 (0-6); 115.05 (0-3); 170.6 (0-4). 3 . 3 . 5 . P r e p a r a t i o n of Z / E - 1 7 a - [ 2 - ( t r i b u t y I s t a n n y I) v i n y i ] e s t r a d i o l

The reaction was carried out as above and the product was obtained as a solid and recrystallised from ethanol

1 7 a -E th y n y le s tra d io l (0.25 g, 0.843 m m ol), Bu3SnH (0.245 g, 0.843 mmol), AIBN (0.08 mmol).

Z

Yield, 0.27 g, (5,5%) M.p 140-141 °0 Found : 0, 66.03; H, 8.60,

Required for: C2oHs202Sn: C 66.08, H, 8.02%

8h (CDCI3) 0.7 - 2.4 (45H, m, steroid and BuaSn - envelope); 2.65 - 2.75 (2H, m, C-6 methylene); 5.84 (1H, d, 3Jh 13.2 Hz, z jiiT g ^ 69.8 Hz, 2 J 1 1 9 73.2 Hz; H-20); 6.75 (1H, d, 3J 13.2 Hz; 3 j l l 7 g „ 138.6 Hz, 3 jll9 s n 145.2 Hz; H-19) 6.7 - 7.2 (3H, m, arom atic protons).

Sc (C D C I3) 9.89 ( I j l l 7 / l l 9 g n 382.2 Hz; C -a); 13.89 (C-5); 27.65

( 3 j l i 7 / i i 9 g „ 86.70 Hz; C-17); 29.58 ( 2 j i i 7 / i i 9 g n 23.5 Hz); 14 - 49 (steroid envelope); 85.38 ( 3 J 1 1 7/ 119g^ 54.8 Hz; C-17); 122.30 (0

-20); 170.77 (C-19); 119.06; 124.18; 126.09; 139.00; 148.00; 152.08 (aryl).