Double-bond isomerisation

Similarly, the introduction of double bonds, isomerisation or hydrolysis are also frequently encountered reactions in central metabolism. Many of these reactions have their analogues in sterol/steroid interconversions. Below we will confine ourselves to a limited number of examples. 

The Pd(II)-catalysed asymmetric carbonylation of olefins with a chiral thiourea as the hgand has been reported recently. Since these ligands are stable in the presence of oxidising agents, they prevent Pd precipitation and double-bond isomerisation (Scheme 35) [141]. 

Janse van Vuuren, M.J., Govender, G.N.S., Kotze, R., Masters, G.J., Pete, T.P. 2005. The correlation between double bond isomerisation, water-gas-shift and acid production during Fischer-Tropsch synthesis. Prepr. Am, Chem. Soc. Div. Pet. Chem. 50 200. 

The intramolecular addition of hydroxyl groups to triple bonds might be utilised in the formation of furane derivatives. Enynols, having the appropriate double bond geometry, underwent ring closure and subsequent double bond isomerisation in the presence of both palladium and ruthenium catalysts to give substituted furans (3.52.),66... 

Depending on the nature of the catalyst, the transition-metal-catalysed isomerisation will proceed by an addition-elimination mechanism or by the formation of a it allyl complex followed by a 1,3-hydrogen shift (Scheme 2.7b). The equilibrium of the isomerisation lies strongly in favour of the propenyl ether because of resonance stabilisation between the oxygen lone pair and the it orbital of the double bond. Isomerisation can also be performed under strongly basic conditions by using potassium f-butoxide in dimethylsulfoxide (DMSO).18... 

The high conversion polymerisation of a-decene gave a monomer fraction which contained 60% a-decene, 35% internal alkenes and 5% methylnonenes. The conclusion was that, in addition to methyl group migration, isomerisation of the double bond could also take place, even with the monomer. As polyalphaolefins derived from internal olefins usually give products with inferior temperature/viscosity properties, double bond isomerisation can be a problem. 

Typical base-catalysed reactions that occur over alkali metal-exchanged zeolites include dehydrogenations, double bond isomerisations, side-chain alkylation of aromatics, conversion of methyl halides and a range of condensations. The reaction of alcohols over zeolites can be used to determine whether acid or base catalysis predominates. Whereas acid forms of zeolites catalyse dehydrations, leading to alkenes and the products of their subsequent reactions, basic sites catalyse dehydrogenations, leading to aldehydes and ketones. 

Scheme 9.20 Double-bond isomerisation on basic sites occurs via a carbanion intermediate.

Double bond isomerisation of alkenes is promoted over basic catalysts, where the carbon skeleton is retained, in contrast to the action of acid catalysts which are important catalysts for skeletal isomerisation. The difference lies in the mechanism, which for basic catalysts involves carbanions, rather than the carbenium ions that form in the presence of acids (Scheme 9.20). 

Hydrocodone (trade name in Germany Dicoditfl, though marketing approval has been withdrawn due to addiction risk) is an opioid as well, with a pharmacology that is comparable to codeine. Particularly pronounced is its antitussive activity. Hydrocodone has higher potency than codeine, and is therefore used for moderate to severe pain. It is formed by palladium- or platinum-catalysed double bond isomerisation of codeine. Hydrocodone production has seen an almost constant upward trend over the past 20 years, teaching 56 tonnes in 2011. It is exclusively manufactured in the United States, where it is used in combination products, e.g. with acetaminophen in Vicodin . [82]... 

Around 1940, cannabinol was isolated independently by Sir Alexander R. Todd (1907-1997) at the University of Manchester and Roger Adams at the University of Illinois. However, it was determined that this compound was not responsible for the psychotropic effects of cannabis, but actually an artefact, which originated by oxidation of THC dru-ing the isolation process. [125] An additional difficulty in determining the structure of THC was, that the double bond isomerises readily in presence of acid into the thermodynamically favoru-ed 8-position. The problem of isolation was simply technical in nature in contrast to the alkaloids, which are readily purifyable by salt formation as crystalline compounds, this is not possible with /4 -tetrahydrocannabmoL... 

For choosing the appropriate isomerisation conditions, it must however be taken into consideration, that double bonds isomerise for stereochemical reasons at various rates, and that the state of equilibrium does not necessarily lie at 100 % in favour of the (all )-isomers (Fig. 7.27). In case of (all )- -carotene, the (13Z)-isomer is the fastest to form, while this isomer accounts for 25 % at the final equilibrium. The (9Z)- and (13Z,13 Z)-isomers are formed at a distinctly slower rate. The proportion of (15Z)-jS-carotene is at equilibrium very small, and in the case of the double bonds at C-7 and C-11, the equilibrium lies exclusively on the side of the ( )-configuration. This has direct implications for the synthetic strategy. 

Sonesson, C., Larhed, M., Nyquist, C. and Hallberg, A. (1996) Regiochemical control and suppression of double bond isomerisation in the Heck arylation of l-(methoxycarbonyl)-2,5-dihydropyrrole. J. Org. Chem., 61, 4756-63. 

Shezad, N., Clifford, A.A. and Ra5mer, C.M. (2001) Suppression of double bond isomerisation in intramolecular Heck reactions using supercritical carbon dioxide. Tetrahedron Lett., 42, 323-5. 

A soln. of lithium naphthalenide in tetrahydrofuran added to a soln. of startg. bis(tricarbonylchromium) complex in 6 1 THF/HMPA at —78° under argon, the dark brown soln. stirred for 30 min, butyl bromide added at room temp., and the mixture decomplexed with iodine at —78° - product. Y 74%. With acyl halides the central double bond isomerises. F.e.s. R.D. Rieke et al., J. Org. Chem. 54, 21-4 (1989). 

In fungal sterol biosynthesis the A - A -double bond isomerisation involves the loss of the 70-hydrogen (derived biosynthetically from the 2-pro-R hydrogen of (-i-)-R-mevalonic acid [MVA]), whereas in animal, higher plant and chlorophyte algal sterol biosynthesis the 7p-hydrogen (ex 2-pro-S H of MVA) is lost. 

Moses and co-workers took this hypothesis one step further, speculating that the original biosynthetic polyene precursor was not the ( ,Z,Z, )-telraene 35 but the all E isomer 40 [17], Furthermore, they postulated that this polyene was the precursor to a number of y-pyrone polypropionate natural products, diversification occurring via selective double bond isomerisations followed by varying electro-cyclisations or cycloadditions. Thus the polyene 40 was synthesised by a Suzuki... 

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