Stereoselectivity olefin hydrogenation

Olefins are hydrogenated very easily, unless highly hindered, over a variety of catalysts. With active catalysts, the reaction is apt to be diffusion limited, since hydrogen can be consumed faster than it can be supplied to the catalyst surface. Most problems connected with olefin hydrogenation involve some aspect of regio- or stereoselectivity. Often the course of reduction is influenced greatly by the catalyst, by reaction variables, and by hydrogen availability at the catalyst surface. 

The hydrogenation of olefins with soluble metal complexes has been studied extensively" 5. This intensive study seems anomalous because soluble catalysts are seldom used for olefin hydrogenation in industry and in organic synthesis. The importance of homogeneous catalysts is great in asymmetiic reactions (L-Dopa, Dual herbicide synthesis) where the high stereoselectivity of optically active catalysts is the major advantage. 

Hydroalumination followed by protonolysis is less convenient for stereoselective cis hydrogenation of the double bond. Simple, vicinally disubstituted double bonds sluggishly undergo hydroalumination and the carbon-aluminum bond undergoes inversion in hydrocarbon solvents at moderate temperatures. Strained olefins are more reactive and can react stereoselec-tively under carefully controlled conditions126. 

Ruthenium catalysts are now widely used for olefin hydrogenation, and many examples of enantioselective ruthenium-catalyzed hydrogenation are discussed in Section 15.7. Here, before addressing the issues of stereoselectivity, the elementary steps of ruthenium-catalyzed hydrogenation are discussed. These catalysts react through monohydride species containing a second anionic ligand. 

Enzyme-catalyzed hydrogenations have a long history as an alternative for stereoselective olefin reduction [12, 72). Selected illustrative examples of enzymatic olefin reductions are depicted below. In an elegant series of studies by scientists at Hoffmann-La Roche, it was found that baker s yeast effects the reduction of unsaturated ester 96 (Scheme 8.10) [73]. Unsaturated alcohol 99 was selectively transformed into lactone 100 by use of the fungus Geotrichum candidum. The optically pure substituted lactones, 98 and 100, were subsequently utilized in a synthesis of a-tocopherol (vitamin E 101) [74]. 

In general, hydroboration—protonolysis is a stereoselective noncatalytic method of cis-hydrogenation providing access to alkanes, alkenes, dienes, and enynes from olefinic and acetylenic precursors (108,212). Procedures for the protonolysis of alkenylboranes containing acid-sensitive functional groups under neutral or basic conditions have been developed (213,214). 

Fluorine and sulfur (in the form of a methylthio group) are added to nucleophilic olefins with Markovnikov regwselectivity and anti stereoselectivity by di-methyl(niethylthio)sulfoninni fluoroborate and triethylamine tris(hydrogen fluoride) [777] (equation 21)... 

Wide variations in stereoselectivity are possible between the and Z isomers (79). In hydrogenation of several ( )- and (Z)-a-acylaminocinnamic acid derivatives, the Z isomers gave greater enantiomeric excesses at 15-100 times the rate of reduction of the isomer, but in all cases the 5 enantiomer was formed in greater excess (//7). The greater effectiveness of Z-olefins is general If8). 

The origin of the remarkable stereoselectivities displayed by chiral homogeneous catalysts has occasioned much interest and speculation. It has been generally assumed, using a lock-and-key concept, that the major product enantiomer arose from a rigid preferred initial binding of the prochiral olefin with the chiral catalyst. Halpren 48) on the basis of considerable evidence, reached the opposite conclusion the predominant product enantiomer arises from the minor, less stable diastereomer of the olefin-catalyst adduct, which frequently does not accumulate in sufficient concentration to be detected. The predominant adduct is in essence a dead-end complex for it hydrogenates at a much slower rate than does the minor adduct. 

The isomerization of an allylic amine to an enamine by means of a formal 1,3-hydrogen shift constitutes a relatively small structural change. However, this transformation could be extremely valuable if it could be rendered stereoselective. In important early studies, Otsuka and Tani showed that a chiral cobalt catalyst, prepared in situ from a Co(ii) salt, a chiral phosphine, and diisobutylaluminum hydride (Dibal-H), can bring about the conversion of certain pro-chiral olefins to chiral, isomeric olefins by double bond migra-... 

Redox-type reactions show by far the worst performance in meeting the golden atom economical threshold. Three reductions meet this criterion with (AE)min values of 1 hydrogenation of olefins using the Lindlar catalyst (1952), Noyori stereoselective hydrogenation reaction (1985), and Zincke disulphide cleavage reaction (1911) whereas, oxidations... 

Prior literature indicated that olefins substituted with chiral sulfoxides could indeed be reduced by hydride or hydrogen with modest stereoselectivity, as summarized in Scheme 5.10. Ogura et al. reported that borane reduction of the unsaturated sulfoxide 42 gave product 43 in 87 13 diastereomer ratio and D20 quench of the borane reduction mixture gave the product 43 deuterated at the a-position to the sulfoxide, consistent with the hydroboration mechanism [10a]. In another paper, Price et al. reported diastereoselective hydrogenation of gem-disubstituted olefin rac-44 to 45 with excellent diastereoselectivity using a rhodium catalyst [10b],... 

Treatment of the olefin 49 with Zeise s dimer leads to the chloroplatination complex 50 [26], The addition adduct 50 is hydrogenated stereospecifically to the trans-disubstituted chlorocyclohexane 51. The insertion of carbon monoxide into 50, in the presence of methanol, yields the ester 52 stereoselectively. 

When a chiral ansa-type zirconocene/MAO system was used as the catalyst precursor for polymerization of 1,5-hexadiene, an main-chain optically active polymer (68% trans rings) was obtained84-86. The enantioselectivity for this cyclopolymerization can be explained by the fact that the same prochiral face of the olefins was selected by the chiral zirconium center (Eq. 12) [209-211]. Asymmetric hydrogenation, as well as C-C bond formation catalyzed by chiral ansa-metallocene 144, has recently been developed to achieve high enantioselectivity88-90. This parallels to the high stereoselectivity in the polymerization. 

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