Alkenes, enantioselective hydrogenation

Another important use for Wilkinson s catalyst is in the production of materials that are optically active (by what is known as enantioselective hydrogenation). When the phosphine ligand is a chiral molecule and the alkene is one that can complex to the metal to form a structure that has R or S chirality, the two possible complexes will represent two different energy states. One will be more reactive than the other, so hydrogenation will lead to a product that contains predominantly only one of the diastereomers. 

Table 6.2 Enantioselective hydrogenation of tri-substituted alkenes catalyzed by [(S,S,S)-(EBTHI)TiX2].a)...

Table 6.18 Enantioselective hydrogenation of alkenes catalyzed by Group III and lanthanide complexes.

Early transition-metal complexes have been some of the first well-defined catalyst precursors used in the homogeneous hydrogenation of alkenes. Of the various systems developed, the biscyclopentadienyl Group IV metal complexes are probably the most effective, especially those based on Ti. The most recent development in this field has shown that enantiomerically pure ansa zirconene and titanocene derivatives are highly effective enantioselective hydrogenation catalysts for alkenes, imines, and enamines (up to 99% ee in all cases), whilst in some cases TON of up to 1000 have been achieved. 

Enantioselective hydrogenation of 1,6-enynes using chirally modified cationic rhodium precatalysts enables enantioselective reductive cyclization to afford alky-lidene-substituted carbocycles and heterocycles [27 b, 41, 42]. Good to excellent yields and exceptional levels of asymmetric induction are observed across a structurally diverse set of substrates. For systems that embody 1,2-disubstituted alkenes, competitive /9-hydride elimination en route to products of cycloisomerization is observed. However, related enone-containing substrates cannot engage in /9-hydride elimination, and undergo reductive cyclization in good yield (Table 22.12). 

This chapter describes, from an historic perspective, the development of ligands and catalysts for enantioselective hydrogenations of alkenes. There is no in-depth discussion of the many ligands available as the following chapters describe many of these, as well as their specific applications. The purpose here is to provide an overall summary and perspective of the area. By necessity, a large number of catalyst systems have not been mentioned. The discussion is also limited to the reductions of carbon-carbon unsaturation. In almost all cases, rhodium is the transition metal to catalyze this type of reduction. In order to help the reader, the year of the first publication in a journal has been included in parentheses under each structure. 

Burk et al. showed the enantioselective hydrogenation of a broad range of N-acylhydrazones 146 to occur readily with [Et-DuPhos Rh(COD)]OTf [14]. The reaction was found to be extremely chemoselective, with little or no reduction of alkenes, alkynes, ketones, aldehydes, esters, nitriles, imines, carbon-halogen, or nitro groups occurring. Excellent enantioselectivities were achieved (88-97% ee) at reasonable rates (TOF up to 500 h ) under very mild conditions (4 bar H2, 20°C). The products from these reactions could be easily converted into chiral amines or a-amino acids by cleavage of the N-N bond with samarium diiodide. 

Enantioselective Hydrogenation of Alkenes with Ferrocene-Based Ligands... 

Enantioselective hydrogenation of functionalized alkenes is a well-developed field. A wide variety of rhodium and ruthenium catalysts and substrates are available for this purpose (see Chapters 23 to 28), and the reaction is widely used as a common synthetic tool in both academia and industry. 

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