Stereochemistry of hydrogenation

The stereochemistry of hydrogenation cannot be determined by studying the reactions of acychc alkenes such as 1-octene. The product of the hydrogenation of 1-octene is octane, a conformationally flexible molecule. When octene is converted to octane, the hydrogen atoms have added to adjacent carbon atoms, but we cannot tell how the individual atoms approached the plane of the alkene molecule. However, the stereochemistry of hydrogenation can be determined with cycloalkenes. 

The hydrogenation of 1,2-dimethylcyclopentene produces c -l,2-dimethylcyclopentane. Therefore, hydrogenation of an alkene occurs by the addition of two hydrogen atoms to the same side of the plane of the double bond. The process is called syn addition. Syn addition can only occur if the cycloalkene remains attached to the metal surface, allowing the two hydrogen atoms to add to the same side of the double bond. 

Linstead et al. explained the selective formation of cw-Yyn-cw-perhydrophnan-threne in the hydrogenation of phenathrene over Adams platinum in acetic acid on the basis that the hydrogen atoms were added to one side of the molecule from the catalyst 

Rylander et al. studied the effect of carriers and water on the stereochemistry of hydrogenation of o-, m-, and / -xylenes over rhodium and ruthenium catalysts at room temperature and an initial hydrogen pressure of 0.44 MPa.66 As seen from the results shown in Table 11.6, carbon-supported catalysts give less trans isomers than do the other supported catalysts. With a few exceptions, rhodium catalysts tend to produce the trans isomers more than do ruthenium catalysts. It is noted that the presence of water greatly reduced the proportion of trans isomer in the hydrogenations of o- and m-xylenes with Ru-C and of p-xylene with Rh-C. 

TABLE 11.5 Stereoselectivities of the Platinum Metals for Formation of the Cis Isomer in the Hydrogenation of o-Xylcnc, and 1,2- and l,6-Dimethylcyclohexenc fc 

TABLE 11.6 Effects of Carriers and Water on the Stereochemistry of Hydrogenation of o-, in-, andp-Xylenes with Rhodium and Ruthenium Catalysts 2  

Siegel et al. observed that, at low hydrogen pressures (0.03-0.2 MPa), about 80% of the initial products from 1,4-di-f-butylbenzene formed over 5% Rh-Al203 in cyclohexane was 1,4-di-f-butylcyclohexene the remainder was v-l,4-di-f-butylcyclo-hexane.69 By means of kinetic analysis, the intermediate 1,4-di-f-butylcyclohexene, which amounted to about 33% at -70% conversion, was estimated to desorb from the catalyst surface to the extent as large as 80% at 30°C and 0.084 MPa H2. v-3,6-Di-f-butylcyclohexene amounted only to 1 % at the maximum. At low pressures, however, over 80% of the 1,4-di-f-butylcyclohexene appeared to be converted to saturated prod- 

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The stereochemistry of hydrogen-deuterium exchange at the chiral carbon in 2-phenylbutane shows a similar trend. When potassium t-butoxide is used as the base, the exchange occurs with retention of configuration in r-butanol, but racemization occurs in DMSO. The retention of configuration is visualized as occurring through an ion pair in which a solvent molecule coordinated to the metal ion acts as the proton donor... 

While the foregoing concepts have been utilized to rationalize the product distribution obtained on hydrogenation of a number of monocyclic olefins, it should be noted that the effect of pressure on the stereochemistry of hydrogenation of steroidal double bonds has not been critically evaluated. 

The product stereochemistry obtained on hydrogenation of a, -unsaturated ketones is generally the same as that observed on saturation of the corresponding desoxy olefin. However, the stereochemistry of hydrogenation of these polarized species can be affected by the nature of the solvent (see section II-C). 

The first step in the reaction is adsorption of Pronto the catalyst surface. Complexation between catalyst and alkene then occurs as a vacant orbital on the metal interacts with the filled alkene tt orbital. In the final steps, hydrogen is inserted into the double bond and the saturated product diffuses away from the catalyst (Figure 7.7). The stereochemistry of hydrogenation is syn because both hydrogens add to the double bond from the same catalyst surface. 

In this type of reaction, called hydrogenation, the regiochemistry will always be irrelevant, regardless of what alkene we use (we are adding two of the same group). However, we do need to explore the stereochemistry of hydrogenation reactions. In order to do this, let s take a close look at how the reaction takes place. 

Dimethylcyclohexene is an example of an alkene for which the stereochemistry of hydrogen chloride addition is dependent on the solvent and temperature. At —78° C in dichloromethane, 88% of the product is the result of syn addition, whereas at 0° C in ether, 95% of the product results from anti addition.8 Syn addition is particularly common with alkenes having an aryl substituent. Table 4.1 lists several alkenes for which the stereochemistry of addition of hydrogen chloride or hydrogen bromide has been studied. 

Solvents regularly used in organic reactions are used in heterogeneous catalysis of organic reactions. When solvent information is known, it accompanies other reaction information in each chapter. It must be remembered, however, that the solvent may interact with the catalyst surface and be converted into something undesirable or may combine with or modify one or more of the reactants. The example in Table 1.351 shows the rather minor effect of solvents on the stereochemistry of hydrogenation of the exo double bond in a spatane precursor. 

Apparent trans addition of hydrogen to a carbon-carbon double bond has been the subject of intense investigations and several mechanism have been proposed the stereochemistry of hydrogenation of alkenes has been comprehensively reviewed by Siegel in 1966,66 by Molnar in 1983,67 and again by Bartok and Molnar in 1997,68 so only a brief history is related here. 

In the case of tri-substituted alkenes, the 1,3-syn products are formed in moderate to high diastereoselectivities (Table 21.10, entries 6—12). The stereochemistry of hydrogenation of homoallylic alcohols with a trisubstituted olefin unit is governed by the stereochemistry of the homoallylic hydroxy group, the stereogenic center at the allyl position, and the geometry of the double bond (Scheme 21.4). In entries 8 to 10 of Table 21.10, the product of 1,3-syn structure is formed in more than 90% d.e. with a cationic rhodium catalyst. The stereochemistry of the products in entries 10 to 12 shows that it is the stereogenic center at the allylic position which dictates the sense of asymmetric induction... 

Beedle, A. S., Munday, K. A., Wilton, D. C. The stereochemistry of hydrogen transfer from NADPH catalyzed by 3-hydroxy-3-methylglutaryl-coenzyme A reductase from rat liver. European J. Biochem. 28, 151—155 (1972). 

Biellmann, J.-F., Rosenheimer, N. Dogfish lactate dehydrogenase The stereochemistry of hydrogen transfer. FEBS Letters 34, 143—144 (1973). 

Explanations of the stereochemistry of hydrogenation have been dominated by ideas concerning the manner in which a given unsaturated compound may best be fitted onto a planar surface from which hydrogen is abstracted. Cis addition is readily understood in such terms. 

The stereochemistry of hydrogenation of 1,2-dimethylcyclQhexene and 1,2-dimethylcyclopentene is instructive. Each of these substances would be expected to yield only the ci5-l,2-dimethylcycloalkane via cis addition. Both cis and trans isomers, however, are formed from either of these two cycloalkenes when hydrogenated in the liquid phase (acetic acid) over reduced platinum oxide—one of the more stereoselective catalysts [57, 58). The ratio of isomers which is produced is a function of the pressure of hydrogen, the proportion of cis increasing with increasing pressure (Fig. 5). This fact implies that the trans isomer is formed via a... 

Similarly, to explain the stereochemistry of hydrogenation of dialkyl-cyclohexenes (other than 1,2 derivatives) at high pressures of hydrogen. 

Although the transition state for the exchange reaction may be described as the critical complex for the conversion of the half-hydrogenated state to either a jr-complexed olefin or an eclipsed vicinal diadsorbed alkane, the stereochemistry of hydrogenation of cycloalkenes on platinum at low pressures can be understood if the transition state has a virtually saturated structure. 

Evidence derived from a study of the stereochemistry of hydrogenation of 1,2-cyclononadiene and 1,2-cyclodecadiene led Moore (108) to conclude that allyl complexes like those postulated above must be intermediates. He noted that, of the four ways in which either allene could be adsorbed on a surface, two, a and b, would yield via cis addition of hydrogen the cis-cycloalkene and two, c and d, the tram isomer. Examination of... 

The Stereochemistry of Hydrogenation of , -Unsaturated Ketones Robert L. Augustine Asymmetric Homogeneous Hydrogenation J. D. Morrison, W. F. Masler, and M. K. Neuberg... 

The stereochemistry of hydrogenation of anhydrovinblastine was initially misassigned. See also ref. 70-74. 

The stereochemistry of hydrogen transfer has been studied with the liver enzyme by using the labeled NAD derivative354 (91). The reduced pyridine nucleotide was shown to have the structure 92, thus indicating that both hydride ions that are transferred from 89a... 

The stereochemistry of hydrogenation, the long recognized predominantly cis addition103-105 (see Section IV.A.3) is also consistent with the stepwise addition of the two H atoms via the half-hydrogenated intermediate. H-D exchange reaction of alkanes is also interpreted with the involvement of the surface alkyl intermediate106,107. 

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