Double bond-migration

Double-bond migration often passes unnoticed, for unless tracers are employed, there may be no direct evidence remaining that migration has occurred. Nonetheless, the fact that it does occur can have a number of important consequences. Selective removal of cis homoconjugated dienes and trienes in natural oils, used to make edible hydrogenated fats, depends mainly on prior isomerization of multiple unsaturation into conjugation under hydrogenation conditions (J9). 

A common consequence of migration in complex molecules is that tetrasubstituted olefins result, which can be hydrogenated only with difficulty, if at all. It is easier to try to prevent hindered olefin formation than it is to correct it. Attempted hydrogenation of the exocyclic methylene group in 15 proved difficult when using an aged 10% Pd-on-C catalyst there was a 

Another example is the hydrogenation of the homoallylic eompound 4-methyl-3-cyclohexenyl ethyl ether to a mixture of 4-methylcyclohexyl ethyl ether and methylcyclohexane. The extent of hydrogenolysis depends on both the isomerizing and the hydrogenolyzing tendencies of the catalysts. With unsupported metals in ethanol, the percent hydrogenolysis decreased in the order palladium (62.6%), rhodium (23 6%), platinum (7.1%), iridium (3.9%), ruthenium (3.0%) (S3). 

The cis ether was always formed in greater amounts than the Crans, but the cis-trans ratio varied considerably with the metal [Pd (2.0), Ru (3.0), Rh (4.0), Ir (4.4), Pt(5.2)]. 

Unsaturated alcohols may be converted to saturated carbonyl compounds as a result of migration (75). When migration relative to saturation is high, the isomerization gains synthetic utility (9,49). 

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The reaction is illustrated by the preparation of cholestenone from cholesterol the double bond migrates from the Py to the ap position during the oxidation ... 

Reactions of allylic systems that yield products m which double bond migration has occurred are said to have proceeded with allylic rearrangement, or by way of an allylic shift... 

Allylic rearrangement (Section 10 2) Functional group trans formation in which double bond migration has converted one allylic structural unit to another as in... 

Megestrol acetate (79) is stmcturaHy related to progesterone (1). It has been prepared from medroxyprogesterone acetate (74) by chloranil-mediated dehydrogenation. It also has been prepared from hydroxyprogesterone acetate (42) via 6-methylenation and double-bond migration (109,110). 

Hydroperoxides have been obtained from the autoxidation of alkanes, aralkanes, alkenes, ketones, enols, hydrazones, aromatic amines, amides, ethers, acetals, alcohols, and organomineral compounds, eg, Grignard reagents (10,45). In autoxidations involving hydrazones, double-bond migration occurs with the formation of hydroperoxy—azo compounds via free-radical chain processes (10,59) (eq. 20). 

In the alternative approach.the 1,3-dipolar system can be constructed in several ways. Treatment of a-chloroacylhydrazones of diaryl ketones and certain aralkyl and dialkyl ketones (382) with NaH in anhydrous THF gives l-(disubstituted methylene)-3-oxo-l,2-diazetidinium inner salts (383). Reaction of (383) with DMAD in methylene chloride gave (384), a 2 1 adduct with loss of CO. Double bond migration in (384) occurred on heating to give (385). The intermediate in the cycloaddition was found to be (386), which on heating lost CO to form a new ylide system which in turn underwent reaction with more DMAD <81JA7743). 

In chlorination, loss of a proton can be a competitive reaction of the cationic intermediate. This process leads to formation of products resulting from net substitution with double-bond migration ... 

Lithium aluminum deuteride treatment of 3j -benzoyloxy-A" -6j -chloro steroids (204) provides another example of double bond migration. This... 

Replacement of halides with deuterium gas in the presence of a surface catalyst is a less useful reaction, due mainly to the poor isotopic purity of the products. This reaction has been used, however, for the insertion of a deuterium atom at C-7 in various esters of 3j -hydroxy-A -steroids, since it gives less side products resulting from double bond migration. Thus, treatment of the 7a- or 7j5-bromo derivatives (206) with deuterium gas in the presence of 5% palladium-on-calcium carbonate, or Raney nickel catalyst, followed by alkaline hydrolysis, gives the corresponding 3j3-hydroxy-7( -di derivatives (207), the isotope content of which varies from 0.64 to 1.18 atoms of deuterium per mole. The isotope composition and the stereochemistry of the deuterium have not been rigorously established. 

The double bond migration in steroid hydrocarbons catalyzed by acids or noble metals (see, for example, ref. 185) will not be discussed here. A general review of nonsteroid olefin isomerization has recently been published. Iron carbonyl has been used to isomerize steroidal dienes. 

The double bond migration which normally occurs on forming ethylene ketals from A -3-ketones has frequently been utilized to form derivatives of the A -system. The related transformation of A -3-ketones into A -3-alcohols is usually accomplished by treatment of the enol acetate (171) (X = OAc) with borohydride. This sequence apparently depends on reduction of the intermediate (172) taking place faster than conjugation ... 

Another route to 5a compounds (57) proceeds from the dienol ether (58) by selective catalytic hydrogenation of the A -double bond with concomitant shift of the 3,4-double bond to the 2,3-position. If the hydrogenation is carried out in the presence of traces of base, double bond migration is suppressed and the difficultly accessible A -enol ethers of 5a-series (59) are thus obtained. 

HOCH2CH2OH, MgS04, PhH, L-tartaric acid, reflux, 20 h. 97% yield. These conditions were optimized for the protection of unsaturated aldehydes to prevent double-bond migration. ... 

Neither deuterium incorporation nor double bond migration occurred when 6-cyano-2,3,4,8,9,9n-hexahydropyrido[2,l-Z)][l,3]oxazine (44) was... 

The overall reaction includes allylic transposition of a double bond, migration of the allylic hydrogen and formation of a bond between ene and enophile. Experimental findings suggest a concerted mechanism. Alternatively a diradical species 4 might be formed as intermediate however such a species should also give rise to formation of a cyclobutane derivative 5 as a side-product. If such a by-product is not observed, one might exclude the diradical pathway ... 

Double-bond migrations during hydrogenation of olefins are common and have a number of consequences (93). The extent of migration may be the key to success or failure. It is influenced importantly by the catalyst, substrate, and reaction environment. A consideration of mechanisms of olefin hydrogenation will provide a rationale for the influence of these variables. 

Catalysts have a profound effect on the extent of double-bond migration. The influence is a property of the metal itself and its structure and is little altered by the support(7 7,7 ). It is related to the relative tendencies of the half-hydrogenated states to reform an unadsorbed olefin. A decreasing ordering of metals for double-bond migration (46) is Pd > Ni Rh Ru Os > Ir - Pt. 

Conversion of 4 to 6 consumes no hydrogen and appears to be a consequence of double-bond migration. In this case, however, the reaction proceeded in two stages, hydrogen addition (5) followed by hydrogen elimination and migration (2S). 

Solvents can have a large influence on the extent of double-bond migration (6). The factors involved are complex as shown in the hydrogenation of methylenecyclohexane, 3-methylcyclohexene, and 4-methylcyclohexene to methylcyclohexane in benzene-ethanol, in peniane, and in ethanol over 5% Pd, 5% Pt, and 5% Rh-on-carbon. The amount of isomerized 2-methylcy-clohexene was measured ai 25% completion and, depending on the system,... 

Hydrogenation of aromatics under mild conditions gives mainly the all-cis isomer as if hydrogen addition takes place from only one side of the molecule (23,24). Reductions under more vigorous conditions may give other isomers by isomerization of the initially formed all-cis product. Under mild conditions, other isomers are accounted for by desorption and readsorption in a new orientation of intermediate olefins, as well as by double-bond migration in the... 

Homoallylic systems may isomerize under hydrogenation conditions to allylic systems, causing hydrogenolysis to occur when it would not have been expected (39b,45a-45c). In these cases, if hydrogenolysis is unwanted, it is best to avoid those catalysts and conditions that favor isomerization. Double-bond migration to an allylic position may occur even if the double bond is required to leave a tetrasubstituted position (26a). 

Selectivity to primary metathesis products is usually less than 100%, as a consequence of side reactions, such as double-bond migration, dimerization, oligomerization, and polymerization. The selectivity can be improved by adding small amounts of alkali or alkaline earth metal ions, or, as has recently been shown, thallium 40), copper, or silver ions (41)-... 

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