Z -Oct-4-ene

These alkene isomers are separately available (4) by treatment of threo-5-trimethylsilyloctan-4-ol, prepared by reduction of the corresponding ketone with DIBAL in pentane at — 120°C, with base or acid. The preparation of 5-trimethylsilyloctan-4-one itself illustrates three general procedures the addition of alkyl lithium reagents to vinylsilanes to generate a-lithiosilanes, the preparation of complex /3-hydroxysilanes, as diastereoisomeric mixtures, and the oxidation of such compounds to /3-ketosilanes 

5-Trimethylsilyloctan-4-ol. To a solution of vinyltrimethylsilane (6.77mmol) in THF (15ml), cooled to —78°C, was added a solution of ethyllithium (8.8 mmol, 1.15 m in ether) with stirring. The mixture was stirred at —78°C for 2 h, wanned to — 30 °C over 1 h, and then cooled again to —78°C. n-Butanal (7.5 mmol) was added, and then the reaction mixture was allowed to come to ambient temperature and stirred for 3 h. It was then partitioned between brine and ether. The layers were separated, and the organic layer was dried, concentrated and the residue distilled (oven temperature 120 °C) to give the / -hydroxysilane (6.3 mmol, 89% based on n-butanal), as a 2 1 mixture of threo and erythro diastereoisomers. 

Base-induced elimination. KH (0.1 g, 50% slurry in oil, 1.25 mmol) was washed with pentane (4ml). To the residue was added THF (5 ml) and the alcohol (0.378 mmol), and the mixture was stirred for lh at ambient temperature. It was then partitioned between ether and saturated ammonium chloride solution, and the ethereal layer was separated, dried and concentrated to give the alkenes as a 95 5 mixture of ( ) (Z) isomers, in 96% yield (g.l.c.). 

Acid-induced elimination. To a solution of the alcohol (0.632 mmol) in THF (10ml) was added concentrated sulphuric acid (2drops), and the mixture was stirred at ambient temperature for 10 h. It was then partitioned between ether and saturated sodium hydrogen carbonate solution. Work-up as above gave the alkenes as an 8 92 mixture of (E) (Z) isomers, in 99% yield 

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To a solution of potassium methoxide (0.2 mmol) in HMPA (10 ml) (CAUTION—CANCER SUSPECT AGENT), heated to 65°C, was added (E)-oct-4-ene oxide (1.2 mmol), then hexamethyldisilane (1.8 mmol) in HMPA (5ml), and the yellow mixture was stirred at 65°C for 3h. The cooled mixture was poured onto saturated brine, and extracted with pentane (2 x 25 ml). The combined organic extracts were dried and concentrated, to give oct-4-ene (1.15 mmol, 96%, 99 1 (Z) (E) by g.I.c.). 

To a stirred suspension of sodium wire (105 mmol, freshly drawn) in ether (100ml) was added TMSCl (63 mmol). The resulting mixture was stirred at ambient temperature for 15 min, and then a solution of (Z)-4-iodo-oct-4-ene (42 mmol, prepared by the reaction of oct-4-yne with HI, isomeric purity 95% (g.l.c.)) in ether (50ml) was added dropwise. The resulting mixture, which turned blue, was stirred at ambient temperature for 24 h, and then quickly filtered through a pad of Celite, and the pad washed with ether. The filtrate was washed with saturated sodium hydrogen carbonate solution, water, and dried. Concentration and distillation afforded (Z)-4-tri-methylsilyloct-4-ene (28 mmol, 67%), b.p. 73-75 °C/18 mmHg, isomeric purity 91.6% (g.l.c.). 

The synthesis of bixin (533) requires the regiospecific introduction of a Z double bond. Attention was first focused on the total synthesis of (all- )-methylbixin (534) [35]. (3-Methylepichlorohydrin (180) was treated with sodium acetylide (68) to give the alcohol 181 which was transformed with dihydropyran and phosphorus oxychloride to the acetylenic compound 182. Condensation of two moles of 182 with oct-4-ene-2,7-dione (5) in the presence of PhLi resulted in the C2o-diol 183. Treatment with p-toluenesulphonic acid first in toluene gave the diether 184 and afterwards in ethanol led to the diol 185, which was oxidized with Mn02 to the dial 186. The Knoevenagel condensation with malonic acid (187) and methylation with diazomethane gave the diester 188, which was hydrogenated in the presence of Lindlar catalyst and isomerized with iodine to (all- )-methylbixin (534) in an overall yield of 0.04% referred to 180 (Scheme 41). 

Dissolving metal reductions works very well with aldehydes and ketones, but alkenes are not readily reduced under the same conditions. For example, 1-hexene is reduced to hexane in only 41% yield with Na/MeOH/liquid NHg.14 Alkynes, on the other hand, are reduced to alkenes in good yield using dissolving metal conditions, and the experimental evidence shows that the -alkene is the major product. In a typical example, 4-octyne (60) is treated with sodium in liquid ammonia, and oct-4 -ene (64) is isolated in 90% yield. None of the Z-alkene is observed in this reaction. The reaction with sodium in liquid ammonia is an electron transfer process similar to that observed with ketones and aldehydes, but how is the E geometry of the alkene product explained ... 

The first Z to E isomerization of a heterocyclic olefin (thiacyclo-oct-4-ene) has been reported. ... 

CN [6/ -[3(Z),6a,7p(Z)]]-7-[[(2-amino-4-thiazolyl)(methoxyimino)acetyl]amino]-3-[2-(4-methyl-5-thiazolyl)ethenyl]-8-oxo-5-thia-1 -azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid (2,2-dimethyl-1-oxopropoxy)methyl ester... 

C,(jH22N203 7239-08-5) see Ttopicamide [6J -[6a,7p(Z)J)-3-[(acetyloxy)methyl]-7-[[2-furanyl(wieth-oxyitnino)acetyl]amino]-8-oxo 5-thia-l-azabicyclo[4.2.0]-oct>2>ene>2-carboxylic acid diphenylmethyl ester... 

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