Stereochemistry of Catalytic Hydrogenation

Although all of the above elements catalyze hydrogenation, only platinum, palladium, rhodium, ruthenium and nickel are currently used. In addition some other elements and compounds were found useful for catalytic hydrogenation copper (to a very limited extent), oxides of copper and zinc combined with chromium oxide, rhenium heptoxide, heptasulfide and heptaselen-ide, and sulfides of cobalt, molybdenum and tungsten. 

Catalytic hydrogenation giving optically active compounds was accomplished over palladium on poly() -S-aspartate) and on poly(y-S-glutamate) [75] and over rhodium on phosphine-containing substrates [16,17,18,19,20. Optical yields up to 93% were reported [76], 

More general statements about catalytic hydrogenation are difficult to make since the results are affected by many factors such as the catalyst, its supports, its activators or inhibitors, solvents [27], pH of the medium [27] (Auwers-Skita rule acidic medium favors cis products neutral or alkaline medium favors Irons products [22]) and to a certain extent temperature and pressure [5]. 

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In spite of the large number of investigations, the characteristic conclusion with respect to the stereochemistry of catalytic hydrogenation of cyclic ketones is that it depends on many factors, namely on the structure of the substrate, the nature of the catalyst and the reaction conditions (solvent, reaction temperature, hydrogen pressure, additives). 

Having controlled the preferred geometry of an allylic system, A( L3) strain influences the stereochemistry of catalytic hydrogenation of substituted allylic alcohols in a manner that is analogous to the control by A -1 2- strain. With the prior... 

Although many details remain uncertain, a rudimentary understanding of the mechanism and stereochemistry of catalytic hydrogenation has been developed. It is... 

A modification of the Auwers-Skita rule for predicting stereochemistry of catalytic hydrogenations has been proposed, with particular reference to the desorption step. It is stated that the isomer formed preferentially has the more (most) masked polar or electron-rich groups. Thus the Auwers-Skita rule predicts formation of trans-ketone (595) from catalytic hydrogenation of (594) i ia purported delivery of hydrogen trans-to angular methyl, whereas in experiment the more compact isomer (596) was formed... 

The stereochemistry of metal-ammonia reduction of alkynes differs from that of catalytic hydrogenation because the mechanisms of the two reactions are different The mechanism of hydrogenation of alkynes is similar to that of catalytic hydrogenation of alkenes (Sections 6 1-6 3) A mechanism for metal-ammonia reduction of alkynes is outlined m Figure 9 4... 

Syn stereochemistry in catalytic hydrogenation. A solid heterogeneous catalyst adds two hydrogen atoms to the same face of the pi bond (syn stereochemistry). 

The catalytic hydrogenation of alkynes is similar to the hydrogenation of alkenes, and both proceed with syn stereochemistry. In catalytic hydrogenation, the face of a pi bond contacts the solid catalyst, and the catalyst weakens the pi bond, allowing two hydrogen atoms to add (Figure 9-2). This simultaneous (or nearly simultaneous) addition of two hydrogen atoms on the same face of the alkyne ensures syn stereochemistry. 

Several factors such as the structure of the substrate, the catalyst, the solvent, the reaction temperature, the pressure of hydrogen and other reaction conditions determine the stereochemistry of the catalytic hydrogenation of cyclic ketones, and it is sometimes difficult to predict the major pn uct of catalytic hydrogenation. One reason for the complexity of the stereochemistry of the hydrogenation of cyclic ketones, at least in part, is related to the isomerization of the products under the reaction conditions. Some cyclohexanols were isomerized in the presence of platinum or nickel catalysts at room temperature or at higher temperature under a hydrogen atmosphere, and the isomerization reached a cis-trans equili-brium. For example, rranj-3,3,5-trimethylcyclohexanol isomerized in the presence of a nickel catalyst. 

Catalytic hydrogenation of 177 provided a variety of products, depending on the reaction conditions. The stereochemistry of the saturated ketoester 183 was not immediately known, but formation of 181 and lactone 182 were reminiscent of Dauben s work. Indeed, X-ray crystallography of 183 revealed the trans-stereochemistry of the hydrogenation product, indicating a predominance of carbomethoxy group directing effect over steric effects. ... 

Given the importance of catalytic hydrogenation reactions, it is not surprising that the oxidative addition of H2 to metal centers is among the best-studied systems. The prototypical reaction of H2 with Vaska s complex to yield the Ir(lll) dihydride derivative Ir(PPh3)2H2(CO)Cl (Scheme 6) displays second-order kinetics, a negative entropy of activation (i.e., an observation consistent with the intermediacy of a a-complex), overall CM-stereochemistry, and negligible solvent effects. 

From the mechanism of catalytic hydrogenation we notice that hydrogen adds to the alkene molecule in such a way that both H-atoms are added to the same side of the molecular plane. The stereochemistry of this reaction is called syn-addition. Addition of halogen follows qnite different stereochemistry two halogen atoms approach the alkene molecular plane from the opposite sides. Such stereochemistry is called anrt-addition. The mechanism is confirmed by the analysis of configurations of products of addition of chlorine to cyclopentene. 

Give the expected major product of catalytic hydrogenation of each of the following alkenes. Clearly show and explain the stereochemistry of the resulting molecules. 

Catalytic Hydrogenation. The mechanism of catalytic hydrogenation apparently consists in the cis-addition of hydrogen atoms to the double bond undergoing saturation with the formation of a quasi-ring (223). It is assumed that the substance undergoing hydrogenation becomes attached to the surface of the catalyst at its least sterically hindered side, i.e., the stereochemistry of the process is determined primarily by the accessibility of the reaction center. 

The results of catalytic hydrogenation are by no means always capable of such a simple interpretation in the majority of cases various other factors must be taken into account. Above all, the stereochemistry of hydrogenation may depend not only on the configuration of the initial sub-... 

Reaction of (T)-(-)-2-acetoxysuccinyl chloride (78), prepared from (5)-mahc acid, using the magnesiobromide salt of monomethyl malonate afforded the dioxosuberate (79) which was cyclized with magnesium carbonate to a 4 1 mixture of cyclopentenone (80) and the 5-acetoxy isomer. Catalytic hydrogenation of (80) gave (81) having the thermodynamically favored aH-trans stereochemistry. Ketone reduction and hydrolysis produced the bicycHc lactone acid (82) which was converted to the Corey aldehyde equivalent (83). A number of other approaches have been described (108). 

Catalytic hydrogenation of the 14—15 double bond from the face opposite to the C18 substituent yields (196). Compound (196) contains the natural steroid stereochemistry around the D-ring. A metal-ammonia reduction of (196) forms the most stable product (197) thermodynamically. When R is equal to methyl, this process comprises an efficient total synthesis of estradiol methyl ester. Birch reduction of the A-ring of (197) followed by acid hydrolysis of the resultant enol ether allows access into the 19-norsteroids (198) (204). 

The strategy of the catalyst development was to use a rhodium complex similar to those of the Wilkinson hydrogenation but containing bulky chiral ligands in an attempt to direct the stereochemistry of the catalytic reaction to favor the desired L isomer of the product (17). Active and stereoselective catalysts have been found and used in commercial practice, although there is now a more economical route to L-dopa than through hydrogenation of the prochiral precursor. 

Catalytic hydrogenation has been utilized extensively in steroid research, and the method has been found to be of great value for the selective and stereospecific reduction of various functional groups. A number of empirical correlations concerning selectivity and product stereochemistry compiled for steroid hydrogenations has been listed in a previous review. ... 

Since the stereochemical course of a catalytic hydrogenation is dependent on several factors, " an understanding of the mechanism of the reaction can help in the selection of optimal reaction conditions more reliably than mere copying of a published recipe . In the first section the factors which can influence the product stereochemistry will be discussed from a mechanistic viewpoint. In subsequent sections the hydrogenation of various functional groups in the steroid ring system will be considered. In these sections both mechanistic and empirical correlations will be utilized with the primary emphasis being placed on selective and stereospecific reactions. 

The reduction of 2-methyl-1,2,3,4-tetrahydro-y-carboline (92) with zinc and hydrochloric acid in the presence of mercuric chloride gives the indolenine derivative, 2-methyl-l,2,3,4,4a,9b-hexahydro-y-carbo-line (93). A related compound, 4,9b-diethyl-2-methyl-l,2,3,4,4a,9b-hexahydro-y-carboline (96), was obtained by catalytic hydrogenation of 95, which was prepared by Fischer ring closure of the phenyl-hydrazone 94. The stereochemistry of the B/C ring junction in these... 

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