Hexenyl acetate isomers

Attempted Synthesis of Specific Hexenyl Acetate Isomers. From Hexanal. Hexanal (5 ml. of 40% technical material) and 25 ml. 2-propenyl acetate were mixed, and 750 mg. p-toluene sulfonic acid was added. This solution was heated at reflux for 12 hours. The solution was then poured into 100 ml. water and extracted with two 50-ml. portions of ether. The combined ether extracts were washed with water, dilute aqueous sodium bicarbonate, and water and dried over sodium sulfate. After evaporating the ether, a gas chromatogram showed two major components present in a 3 2 ratio (probably the trans- and cis-hex-l-en-l-ol acetates, respectively). These components had identical retention times in the gas chromatograms to two of the major components present in the hexene-1 vinylation reactions. 

Problems in characterizing and rationalizing these products are immediately apparent. It is necessary to know whether they are primary reaction products or products of isomerization or other secondary reactions, and it is desirable to know as far as possible the specific structures of the products even though 25 hexenyl acetate isomers (ester and ole-finic positional) are possible. In addition, the structures of the high boiling products must be elucidated, and a reasonable explanation for their formation presented. 

Several approaches were taken. Capillary-column gas chromatography on a vinylation reaction product showed 24 separate peaks present in the hexenyl acetate fraction however, six of the peaks accounted for about 90% of the total sample. Hydrogenation of the reaction mixture (hydrogen over platinum on carbon) reduced the hexenyl acetates to a mixture of three hexyl acetates and thereby greatly simplified determining the position of oxygen substitution with, however, loss of information on olefin position. We tried to synthesize the specific hexenyl acetate isomers by the ester interchange reactions (Reactions 7a, 7b, and 7c). Mixtures of isomers were obtained, but they corresponded to the main components of the vinylation reaction mixture. For example, the main products isolated from the vinylation of hexene-1 corresponded to the products from Reactions 7a and 7b—i.c., vinyl rather than allyl esters. 

To 2 mmol of freshly prepared ethereal LiCu(C.H3), are added 154 mg (1 mmol) of ( — )-m-5-melhyl-2-cyclo-hexenyl acetate (3a). [a]25 —2.7 (c = 3, CHC1,), in a centrifuge tube at 0°C. The mixture is kept at 0 °C for 8 h after which 1 mL of water is added. Methane is evolved and a reddish precipitate forms. After centrifuging, the supernatant liquid is decanted and concentrated, and the product trims-4 is isolated by preparative GC. Isolated yields range from 30% and 40%. However, it was reported in a similar reaction that the yields range from 90% and 95% 5. Analysis by capillary GC shows the product to be 99.5% trans-4 and 0.5% t -4. Capillary GC of the starting 3a shows the acetate 3a to be homogeneous except for a trace ( — 1.0%) of the trans-isomers. 

It is now possible to understand the curious phenomenon whereby the reaction of palladium acetate with I in vacuo first rapidly produces a metal precipitate and then slows at about 20% conversion and finally stops with much of the palladium (II) unreacted. These stages in the reaction correspond to oxidation first by Pd3(OAc)6 and then by IVa with ultimate formation of the inert species Va. A complex mixture of hexenyl acetates is formed in the oxidation of which the major constituent l-hexen-2-yl acetate (VI) is 0.68 mole fraction of the whole mixture. Overall the mixture is closely similar to that obtained in the catalytic reactions of 02 described later, suggesting that the same active palladium-containing species is involved. Much of I is isomerized to a 5 1 mixture of trans- and ds-2-hexene (85% at 6 hrs) with only 3% each of the 3-hexene isomers. This aspect of the selectivity problem in which only one shift of the double bond takes place is also reproduced in the catalytic reaction, but oxygen suppresses the rate of isomerization relative to oxidation. 

Tandem Oxidative Cydization of 4 to Afford 8. The utility of tandem cyclizations in which both addends are alkenes was demonstrated in the synthesis of bicyclo[3.2.1]octanone 8 (29, 36, 47). Oxidation of 4 with 2 equivalents of Mn(OAc)3 and 1 equivalent of Cu(OAc)2 in acetic acid afforded 86% of 8. Oxidation of 4 generated the a-keto radical 5 that underwent 6-endo cydization to afford tertiary radical 6. 5-Exo cydization of 5-hexenyl radical 6 provided primary radical 7 as a 2 1 mixture of exo and endo isomers. Oxidation of both stereoisomers of 7 by Cu(OAc)2 yielded alkene 8 and Cu(OAc), which was reoxidized to Cu(OAc)2 by the second equivalent of Mn(OAc)3. This process is therefore catalytic in Cu(OAc)2 but consumes 2 equivalents of Mn(OAc)3. Since this reaction proceeded selectively in very high yield, our initial goal was to make this reaction catalytic in Mn(OAc)3 by either electrochemical or chemical oxidative regeneration of Mn(ni) in the reaction mixture. 

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