Catalytic hydrogenation stereoselectivity

Asymmetric Hydrogenations. Catalytic asymmetric hydrogenations of p-disubstituted-a-phenylacrylic acids have been achieved using the Rh complex of (4) (eq 9). Asymmetric hydrogenation of unsymmetrically substituted trisubstituted acrylic acids leads to the formation of two stereocenters in high ee. The variation of the terminal dialkylamino substituents has little effect on enantioselectivity. A study of a Ru° complex of (1) was reported as a model for understanding the stereoselective transition state of asymmetric hydrogenations. ... 

PROBLEM 6.13 Hydroboration-oxidation of a-pinene (page 213), like catalytic hydrogenation, is stereoselective. Addition takes place at the less hindered face of the double bond, and a single alcohol is produced in high yield (89%). Suggest a reasonable structure for this alcohol. 

Increasing interest has been shown in recent years for the synthesis of biologically active secondary alcohols by homogeneous catalytic stereoselective and enantioselective hydrogenation reactions. 

Depending on the stereoselectivity of the reaction, either the R or the 5 configuration can be generated at C-2 in the product. This corresponds to enantioselective synthesis of the D and l enantiomers of a-amino acids. The hydrogenation using stereoselective chiral catalysts has been carefully investigated. The most effective catalysts for the reaction are rhodium complexes with chiral phosphine ligands. Table 2.1 records some illustrative results. The details of the catalytic mechanism need not be considered here. The fundamental point is that the chiral environment at the catalytic... 

SCHEME 30.31. Catalytic transfer hydrogenation in stereoselective synthesis. 

The Birch reductions of C C double bonds with alkali metals in liquid ammonia or amines obey other rules than do the catalytic hydrogenations (D. Caine, 1976). In these reactions regio- and stereoselectivities are mainly determined by the stabilities of the intermediate carbanions. If one reduces, for example, the a, -unsaturated decalone below with lithium, a dianion is formed, whereof three different conformations (A), (B), and (C) are conceivable. Conformation (A) is the most stable, because repulsion disfavors the cis-decalin system (B) and in (C) the conjugation of the dianion is interrupted. Thus, protonation yields the trans-decalone system (G. Stork, 1964B). 

The most common stereoselective syntheses involve the formation and cleavage of cyclopentane and cyclohexane derivatives or their unsaturated analogues. The target molecule (aff-cts)-2-methyl-l,4-cyclohexanediol has all of its substituents on the same side of the ring. Such a compound can be obtained by catalytic hydrogenation of a planar cyclic precursor. Methyl-l,4-benzoquinone is an ideal choice (p-toluquinone M. Nakazaki, 1966). 

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. 

Reduction of isoindoles with dissolving metals or catalytically occurs in the pyrrole ring. Reduction of indolizine with hydrogen and a platinum catalyst gives an octahydro derivative. With a palladium catalyst in neutral solution, reduction occurs in the pyridine ring but in the presence of acid, reduction occurs in the five-membered ring (Scheme 38). Reductive metallation of 1,3-diphenylisobenzofuran results in stereoselective formation of the cw-1,3-dihydro derivative (Scheme 39) (80JOC3982). 

The intramolecular cyclization of enolate of l-tryptophyl-3-((3-ketobutyl) pyridinium bromide (160) afforded enamine 161, which undergoes stereoselective acid cyclization with cone. HCl to give the pentacyclic ketone 162 (Catalytic hydrogenation of 162 led to (d,l)-pseudoyohimbone (163) (76JA3645). Again, H3-H15 were found to have the tmns configuration in 162. 

H )-Euranones are useful building blocks in the synthesis of a variety of organic compounds. In addition, they often serve as valuable synthetic intermediates in the stereoselective construction of substituted y-butyrolactones via conjugated addition to the Q ,/3-unsaturated carbonyl moiety or catalytic hydrogenation of the double bond (88JOC1560). 

A very efficient and universal method has been developed for the production of optically pue L- and D-amino adds. The prindple is based on the enantioselective hydrolysis of D,L-amino add amides. The stable D,L-amino add amides are effidently prepared under mild reaction conditions starting from simple raw materials (Figure A8.2). Thus reaction of an aldehyde with hydrogen cyanide in ammonia (Strecker reaction) gives rise to the formation of the amino nitrile. The aminonitrile is converted in a high yield to the D,L-amino add amide under alkaline conditions in the presence of a catalytic amount of acetone. The resolution step is accomplished with permeabilised whole cells of Pseudomonas putida ATCC 12633. A nearly 100% stereoselectivity in hydrolysing only the L-amino add amide is combined with a very broad substrate spedfidty. 

Triple bonds can be reduced, either by catalytic hydrogenation or by the other methods mentioned in the following two sections. The comparative reactivity of triple and double bonds depends on the catalyst. With most catalysts, (e.g., Pd) triple bonds are hydrogenated more easily, and therefore it is possible to add just 1 mol of hydrogen and reduce a triple bond to a double bond (usually a stereoselective syn addition) or to reduce a triple bond without affecting a double bond present in the same molecule. A particularly good catalyst for this purpose is the Lindlar catalyst (Pd-CaCOs—PbO). An alternative catalyst used for selective hydrogena-... 

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