REQUERIMIENTOS TECNOLOGICOS

D ib u ty ltin c h lo rid e h y d rid e was g e n e ra te d fro m d ib u ty ltin d ich lo rid e and d ib u tyltin d ihydride by the d isp rop o rtio n a tio n m ethod. D ibutyltin dichloride was obtained from the A ldrich Chem ical Com pany w hilst dibutyltin dihydride was obtained by van der Kerk's m ethod.3

5 . 4 . 1 P r e p a r a t i o n of ( Z ) - 4 - d i b u t y I c h l o r o s t a n n y 1-2 - m e t h y l - 3 - b u t e n - 2 - o l a n d 3 - d i b u t y l c h l o r o s t a n n y l - 2 - m e t h y l - 3 - b u t e n - 2 - o l .

The above com pounds were obtained by three different methods, firstly at 80°C using AIBN as a radical in itiator, secondly conducting the reaction betw een -25°C and 25°C w ith o u t radical in itia to r and finally by the in situ generation of BuaSnHCI from NaBH4. and Bu2S n C l2-

Method 1.

2-M ethyl-3-butyn-2-ol (0.18 g, 2.245 mmol) in toluene (20 cm3) was added dropwise over 10 minutes to a solution of Bu2S n C l2 (0.082 g, 2.245 mmol) and Bu2S n H2 (0.56 g, 2.215 mmol) in toluene with AIBN (0.2245 mmol). The reaction mixture was heated at 80°C for 3 hours and follow ed by tic with n-hexane-ethyl acetate (6:4 v/v) as eluent.

The solvent was removed in vacuo and the re sulta n t oil was purified by colum n chrom atography using n-hexane-ethyl acetate as e lu e n t.

The proton NMR spectrum of the product showed that the Z- and a - isomers were obtained in a 4:1 ratio:

B u2S n C l2 (0.452g, 1.486 mmol) in monoglyme (10 ml) was added dropw ise to solution of NaBH4 (0.2896 g, 7.65 mmol) in glyme (40 cm3) at -10°C to -15°C. To this solution was added 2-m ethyl-3-butyn-2-ol (0.25 g, 2.97 mmol). The reaction mixture was stirred at -15°C for 30 m inutes and then slowly warmed to room tem perature.

The so lve n t was rem oved in vacuo at 0°C and the product extracted by washing with diethyl ether (3 x 50 cm3).

Removal of the ether left a colourless oil, proton NMR spectrum of which showed that the Z and a isomers had been obtained in a 2:1 r a tio .

Met hod 3.

Using the same mole ratio of reactants as in Method 1 w ithout AIBN, the reaction was repeated at -25°C to give a 1:1 ratio of Z- and a -is o m e rs and at 25°C to give a 2:1 ratio of Z- and a -is o m e rs . The Z- and a -is o m e rs were separated by flash column chrom atography using n- hexane-ethyl acetate (6.5 - 3.5 v/v).

Yield, 0.588 g, (98%)

ÔH (CDCI3) 0.8 - 1.63 (24 H, m, 2 X C4H9 and 2 x CH3)

Z - i s o m e r

Found: C, 44.10; H, 7.85, C l,10.30,

Required for: C i3H 2 7 0SnCI; 0, 44.17; H, 7.70; 01, 10.03%

-3). ÔC (C D C I3 ); 13.65 (Cô); 21.59 ( lJ ll^ S n 456.3 Hz, 477.5 Hz; C-a); 30.04 (C-1); 75.59 ( 3 j i l 7 / l l 9 g n 39.0 Hz; 0-2); 128.91 561.5 Hz, l J l l 9 s n 586.7 Hz; 0-4); 150.51 (0-3). a - l s o m e r ÔH 5.72 (1H, s, 3 J ll7 s n 97.5 Hz, 3 jH 9 s n 102.0 Hz; H-4A); 5.81 (1H, s, 192.9 Hz, 3 jH 9 s n 201.7 Hz; H-4B). ÔC 80.03 (1Jll^Sn 450.7 Hz. 480.0 Hz; 0-a); 26.19 ( 3 J 1 1 7 / I i 9 s n 76.4 Hz; 0-y), 27.82 (J2 1 17 / 1 1 9g^ 30.36 Hz; 0-p); 70.07 (3J117/Il9sn 39.6 Hz; 0-2); 122.06 (0-4); 164.78 (0-3). 5 . 4 . 2 ( Z ) / ( E ) - 4 - ( d i b u t y l c h l o r o s t a n n y l ) - 2 - ( t r i m e t h y l s i l y l o x y ) - 2 - m e t h y l - 3 - b u t e n e a n d 3 - ( d i b u t y l c h l o r o s t a n n y l ) -2 - ( t r i m e t h y l s i l y l o x y ) -2 - m e t h y l- 2 - b u t e n e .

The above products were obtained by Method 3 using 2-methyI-2- (trim e th y ls ily lo x y )-3 -b u ty n e . (0.500g, 3.20 mmol) Bu2S n O l2 (0.486 g, 1.60 mmol) and Bu2S n H2 (0.358, 1.60 mmol), and separated by flash colum n chrom atography using n-hexane-ethyl acetate (6:4 v/v).

Yield 0.954 g, (70%)

Z - i s o m e r

ÔH 5.95 (1H, d, 3Jh 12.2 Hz, 2 jii7 g ^ 74.8 Hz, 2 jii9 g ^ 78.4 Hz; H -4); 6.49 (1H, d, 3Jh 12.2 Hz, 3 jl1 7 g ^ 194.0 Hz, 3j119g^ 203.0

415.0 Hz; C-a); 26.65 (3J117/Il9gn 74.68; C-y); 27.95 ( 2 j l l 7 / l i 9 g „ 30.0 Hz; C-P); 30.76 (0 -1 ); 76.86 (3 J1 1 7 /Il9 g n 28.4 Hz; 0-2); 126.06 (IJ H ^ s n 561.0 Hz; ijH S g n 588.0 Hz; 0 -4); 152.38 (0-3). E - i s o m e r 5h 6.11 (1H, d, 3Jh 18.9 Hz, 2 j i i 7 g „ 75.9 Hz, 2 j i i 9 g „ 79.5 Hz; H- 4); 6.27 (1H, d, 3Jh 18.9 Hz, 3 j i l 7 g „ 95,4 Hz, 3 j l l 9 g „ 99.3 Hz; H-3). 5c 76.86 ( 3 J 1 1 7 / 1 1 9 28.4 Hz; 0-2); 122.86 ( 1 J H 7 534.0 Hz, 2J11.9 562.0 Hz; 0-4); 150.8 (0-3). a - l s o m e r Found: 0, 46.10; H, 8.47; 01, 8.14

Required for: OieHasOSiSnOI, 0 , 45.15; H, 8.28; 01 8.33%

5h 5.65 (1H, s, 2 jll7 g n 98.2 Hz, 3j119gn 102.9 Hz; H -4*); 5.71 (1H, s, 3 jll7 g n 192.9 Hz, 3 jll9 g n 201.8 Hz; H-4B).

5c 81.79 (3J117/I19gn 28.4 Hz; 0-2); 121.71 (2J117/I19gn 16.1 Hz; 0-4); 167.70 (1J” 7g„ 538.2 Hz; 1J’ l9 s n 563.4 Hz; 0-3).

5 . 4 . 3 P r e p a r a t i o n of ( E ) - 4 - d i b u t y I c h l o r o s t a n n y 1-2,2 - d l m e t h y l - 3 - b u t e n e

T his com pound w as obtained by M ethods 1 and 2 w ith the follow ing mol ratio of reactants:

By Method 1.

B u2S n C l2 (0.93 g, 3.043 mmol), Bu2S n H2 (0.68 g, 3.043 mmol) and 3 ,3-dim ethyl-1-butyne (0.5 g, 6.086 mmol). The proton NMR spectrum of the crude product showed that there were two products, the E- sta n n ylvin yl adduct and 3 ,3-dim e th yl-1-b u te n e in a 9:1 ratio. A fter colum n chrom atography the latter com pound was not observed. The E- adduct was obtained as an oil.

Yield, 1.48 g, (70%).

By Method 2.

3 ,3-D im ethyl-1-butyne (0.25 g, 3.043 mmol), Bu2S n C l2 (0.925 g, 3.043 mmol), NaBH4 (0.593 g, 15.67 mmol), glyme (30 cm3).

A fter ether extraction, the pure E-isom er was obtained as the only adduct.

Yield, 0.89 g, (84%).

E - I s o m e r

Found: C, 47.80, H, 8.35, Cl, 9.95,

5h (CDCI3); 0.9 - 1.95 (27 H, m, 2 X C4H9): 5.89 (1 H, d. 3Jh 19.2 Hz, 3 jll7 s n 113.5 Hz. 3 jl1 9 g n 118.6 Hz: H-3); 6.18 (1H, d, 3Jh 19.2, 2 j1 l7 g n 90.2 Hz, 2 j l l 9 g „ 94.6 Hz; H-4). 5c 13.58 (C-5); 17.52 ( iJ ll? s n 364.5 Hz, iJ H S s n 381.5 Hz; C -a); 26.67 (3J117/Ii9sn 66.4 Hz; C - y ) \ 17.69 ( 2 jll7 / ii9 g n 24.1 Hz; C-P); 29.46 (C-1); 120.63 ( iJ ll^ s n 447.4 Hz, lJ li9 g n 467.7 Hz; C-4); 162.34 (C-3). 5 . 4 . 4 Pr e pa r a t i on of 1 7 a - 2 - ( d l b u t y I c h l o r o s t a n n y l v l n y l ) ] e s t r a d i o l - 3 - a c e t a t e

The above compound was only obtained by Method 3 where 17a- e th y n y le s tra d io l-3 -a c e ta te (0.043 g, 0.12 mmol) B uaS nC Ia (0.039 g, 0.128 mmol) and Bu2S n H2 (0.028 g, 0.127 mmol) were reacted together under inert conditions at room temperature.

The reaction was follow ed by tic with n-hexane-ethyl acetate (6:4 v/v) as eluent. When the reaction was com plete the solvent was removed in vacuo and the residue was chrom atographed on a silica gel colum n with n-hexane-ethylacetate as eluent to give the (Z)-isom er exclusively, which was then recrystallised from acetone.

Yield: 62 mg, (80%). M.p 192 - 196°C

Found: C, 59.10; H, 7.51 ; Cl; 5.85

Required for: G3oH4 5 0 3SnCI: 0 , 59.18; H, 7.46; 01, 5.83.

ÔH (CDCI3); 0.98-2.30 (36H, m, steroid envelope, 2 x C4 H9); 2.81 (3H, t, OCH3), 4.60 (1H, s, OH); 6.73 (1H, d, 4Jh 1.4 Hz, 3Jh 12.1 Hz, 3 jll7 s n

92.2 Hz, 2j119sn 96.5 Hz; H-4). ôc 13.68 {C-5); 14.05, 20.64 (IJ H ^ g n 449.8 Hz, lJ H 9 s n 470.3 Hz; C-a); 21.03, 23.32; 24.05; 24.26; 24.20; 27.32 (3J117/Il9g^ 29.0 Hz; C-y); 28.11 (2J117/Il9sn 27.8 Hz; C-p); 28.98; 32.38; 38.26; 39.86; 42.98; 46.51; 46.87; 88.06 (3J117/Il9g^ 23.4 Hz; C-17); 11 2.3 4; 114.50; 124.03; 128.91 (C-20); 132.16; 138.06; 144.67; 154.00 (C-19); 170.38. 5 . 4 . 5 P r e p a r a t i o n of ( Z ) - 2 - ( d l b u t y l c h l o r o s t a n n y l ) - 2 - b u t e n e - 2 , 3 - d i c a r b o x y l i c a c i d

The above com pound was prepared according to M ethod 3 with acetylene dicarboxylic acid (0.2 g, 1.75 mmol), Bu2S n H2 (0.195 g, 0.88 mmol) and Bu2S n C l2 (0.266 g, 0.876 mmol) in ether. Evaporation of the s o lv e n t le ft a yellow visco u s o il, w hich s o lid ifie d a fte r 4 hours refrigeration. The solid was purified by flash colum n chrom atography w ith n -h e x a n e -e th y la c e ta te (6 5 :3 5 v /v ) as e lu e n t, and then re c ry s ta llis e d from d im e th ylfo rm a m id e .

Yield, 0.47 g, (70%), M.p >285°C

Found: C, 37.65; H 5.55, Cl, 9.25

Required for: C i2H2i0 4SnCI; C, 37.59; H, 5.52; Cl, 9.25.

ÔH (CDCI3): 0.85 - 1.70 (18H, m, 2 X C4H9); 6.68 (1H, s, 3Jl17gn 156.2

5c 13.51(0-5); 19.24 ( l j l l 7 s n 516.2 Hz, ijH S g n 540.2 Hz; C-a); 26.45 (3 J ll7 s n 88.0 Hz, S jllS g n 92.1 Hz; C-y); 27.59 (2J117/Il9g^ 32.4 Hz; C-P); 168'74 (1 J ll7 g n 359.8 Hz, 1j119sn 376.5 Hz; C-3); 133.56 (C- 2)170.52 (2J117/Il9gn 24.9; C-4); 172.15 (3Jsn 12.5 Hz; C-1). 5 . 4 . 6 P r e p a r a t i o n of d i m e t h y l ( Z ) - 3 - d l b u t y i c h i o r o s t a n n y l - 2 - b u t e n e - 2 , 3 - d l c a r b o x y l a t e

The above compound was synthesised by Method 3 with dimethyl acetylene dicarboxylate (0.5 g, 0.43 ml, 3.52 mmol), Bu2S n C l2 (0.53 g, 1.74 mmol) and Bu2S nH2 (0.34, 1.75 mmol).

The reaction was follow ed by tic with n-hexane-ethyl acetate (7.5 : 2.5 v/v) as eluent and when complete the solvent was evaporated and the viscous oil was column chrom atographed on silica gel with n- hexane-ethyl acetate (6:3 v/v) as eluent.

Yield, 0.138 g, (80%)

Found: C, 40.50; H, 6.05; Cl, 8.41

Required for: C i4H2504SnCI: 0, 40.86, H, 6.12; 01, 8.62%.

M.S. m/z; 418 ; 376 (M-CI).

ÔH (CDCI3); 0.85-1.68 (18H, m, 2 X C4H9); 3.85 (6H, d, 2x CH3);

6.79 (1H, s, 3j117sn 117.6 Hz, 3 jH 9 s n 123.0 Hz; H-2).

ÔC (CDCI3); 13.51 (C-Ô); 19.56 (lJ l1 ^S n 516.3 Hz, 540.2 Hz; C-a); 26.25 ( 3 jil7 / ii9 g n 95.6 Hz; C-y); 27.60 ( 2 jll7 / ll9 g n

( 2 J 1 1 7 / I l 9 g „ 3 1 , 2 Hz; C=0); 172.56