Stereospecificity catalytic hydrogenation

Two stereochemical aspects—stereospecificity and stereoselectivity—attend catalytic hydrogenation. Stereospecificity will be considered more fully in the next chapter, but we can apply one of its principles—that the stereochemical outcome of a particular reaction depends on the stereochemistry of the reactants—to catalytic hydrogenation. According to Mechanism 6.1, even though the two hydrogen atoms are not transferred from the catalyst surface to the double bond simultaneously, both do add to the same face of the double bond. This is called syn addition and is one of several terms applied to stereospecificity. Its counterpart—anti addition—signifies addition to opposite faces of a double bond. 

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 addition is therefore stereospecifically syn and, like catalytic hydrogenation, generally takes place from the less-hindered side of a double bond, though not much discrimination in this respect is observed where the difference in hulk effects is small.Diimide reductions are most successful with symmetrical multiple bonds (C=C, C=C, N=N) and are not useful for those inherently polar (C=N, C=N, C=0, etc.). Diimide is not stable enough for isolation at ordinary temperatures, though it has been prepared as a yellow solid at — 196°C. 

Hydrogenolysis of epoxides to alcohols by catalytic hydrogenation over platinum requires acid catalysis. 1-Methylcyclohexene oxide was reduced to a mixture of cis- and /ranj-2-methylcyclohexanol [652]. Steroidal epoxides usually gave axial alcohols stereospecifically 4,5-epoxycoprostan-3a-ol afforded cholestan-3a,4/J-diol [652 ]. 

In ethyl 3-keto-2-oximino-3-phenylpropanoate catalytic hydrogenation over palladium on carbon reduced both the keto and oximino group, giving a 74% yield of ethyl ester of -phenylserine (ethyl 2-amino-3-hydroxy-3-phenylpropionate). The reduction is stereospecific and only the erythro dia-stereomer was obtained, probably via a cyclic intermediate 11097]. Similarly, hydrogenation over Raney nickel at 25-30° and 1-3 atm converted ethyl a-oximimoacetoacetate quantitatively to ethyl 2-amino-3-hydroxybutanoate [45]. 

The carbon-nitrogen double bond of A1-piperideines is susceptible to reduction. This can be useful for the stereospecific introduction of ring substituents. An illustration is the preparation of ds-2,6-disubstituted piperidines (211) by catalytic hydrogenation of the corresponding A1-piperideine (210) (77T1569). 

A very efficient, stereospecific synthesis of DL-ribose was based26 on the use of l,l-diethoxy-5-(tetrahydropyran-2-yloxy)-2-pentyn-3-ol as the substrate. Catalytic hydrogenation of this alkyne to the cts-alkene was accompanied by cyclization, to give 2-ethoxy-2,5-dihydro-5-(tetra-hydropyran-2-yloxy)furan (35). cis-Hydroxylation of the double bond in 35 was effected with potassium permanganate, yielding the ethyl DL-ribofuranoside derivative 36, which was hydrolyzed to DL-ribose. 

In the catalytic hydrogenation, two new C—H a bonds are formed simultaneously from H atoms absorbed into the metal surface. Thus, catalytic hydrogenation is stereospecific, giving only the syn addition product. If the atoms are added on the same side of the molecule, the addition is known as syn addition. If the atoms are added on opposite sides of the molecule, the addition is called an anti addition. For example, 2-butene reacts with H2 in the presence of a metal catalyst to give n-butane. 

Palladium on charcoal (Pd/C) is commonly used in the catalytic hydrogenation of pyrimidines in acidic media to form 1,2,4,5-tetrahydro derivatives which are stabilized as amidinium salts (62JOC2170, 65JCS1406). Platinum effects hydrogenation of the 5,6-double bond of uracils, for example, in the addition of deuterium to produce [5,6-2H2]5,6-dihydrouracil. The use of rhodium-on-charcoal and Raney nickel also gives good results. The addition of hydrogen to the 5,6-bond of thymidine and other 5-substituted uridines is stereospecific with rhodium-on-alumina as catalyst. 

In general, a catalytic reaction may be named by adding the adjective catalytic to the standard chemical term for the reaction, for example, catalytic hydrogenation (or, if clarity demands, heterogeneous catalytic hydrogenation), catalytic hydrodesulphurisation, catalytic oxidative dehydrogenation, catalytic stereospecific polymerisation. 

There are other stereospecific olefin addition processes which occur with cis or syn stereochemistry. Common examples include catalytic hydrogenation, hydroboration/oxidation, and dihydroxylation using osmium tetroxide. The stereospecificity of these syn additions requires that die facial properties of the olefinic bond be maintained throughout die addition process and that both new bonds are formed to the same face of the olefin. This is normally accomplished by a concerted syn addition to the n system. 

When catalytic hydrogenation of the enonolactone 122 was performed with deuterium, stereospecific labeling took place at C-3 and at the 2R position of ascarylose.197... 

The alternative approach to the determination of the stereochemistry of hydroxylation )3 to the nitrogen occurring in the biosynthesis of haemanthamine involved the synthesis of stereospecifically labeled tyrosine. Catalytic hydrogenation of suitable acylaminocinnamic acids labeled with isotopic hydrogen in fi position proceeds stereoselectively to furnish an equimolecular mixture of L-(/3i -3H]-and D-[j8 -3H]tyrosine (419) and (420). Enzymic resolution of the racemic amino acid yielded the L and d isomers. The two optically active forms of tyrosine were... 

It was hoped that the resulting benzylic carbinols 59 could be stereose-lectively reduced by catalytic hydrogenation to the required protected kainoid derivatives 60 (Scheme 24). The reduction of benzylic alcohols varies in stereospecificity depending on the catalyst employed.53 Hydrogenation over Raney nickel generally proceeds via retention of configuration, whereas hydrogenation over palladium on charcoal leads to inversion at the benzylic carbon. 

A chemist allows some pure (2S,3R)-3-bromo-2,3-diphenylpentane to react with a solution of sodium ethoxide (NaOCH2CH3) in ethanol. The products are two alkenes A (cis-trans mixture) and B, a single pure isomer. Under the same conditions, the reaction of (2S,3S)-3-bromo-2,3-diphenylpentane gives two alkenes, A (cis-trans mixture) and C. Upon catalytic hydrogenation, all three of these alkenes (A, B, and C) give 2,3-diphenylpentane. Determine the structures of A, B, and C, give equations for their formation, and explain the stereospecificity of these reactions. 

Any method of making such bicyclic compounds will automatically form this stereochemistry. An important method of stereochemical control that we have not used so far in this chapter is catalytic hydrogenation of alkenes, which adds a molecule of hydrogen stereospecifically cis. If the reaction also makes a fused ring system, it may show stereoselectivity too. Here is an example with 5/5 fused rings. 

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