Asymmetric hydrogenation

In 1956 a heterogeneous catalyst made of palladium deposited on silk was shown to effect asymmetric hydrogenation. Later, in 1968, the groups of William Knowles and Leopold Horner independently published the examples of asymmetric hydrogenation using a homogeneous catalysts. While exhibiting only modest enantiomeric excesses, these early reactions demonstrated feasibility. By 1972, enantiomeric excess of 90% was achieved, and the first industrial synthesis of the Parkinson's drug L-DOPA commenced using this technology. The field of asymmetric hydrogenation continued to experience a number of notable advances. Henri Kagan developed DIOP, an easily prepared C2-symmetric diphosphine that gave high ee's in certain reactions. Ryōji Noyori introduced the ruthenium-based catalysts for the asymmetric hydrogenated polar substrates, such as ketones and aldehydes. The introduction of P,N ligands then further expanded the scope of the C2-symmetric ligands, although they are not fundamentally superior to chiral ligands lacking rotational symmetry. Today, asymmetric hydrogenation is a routine methodology in laboratory and industrial scale organic chemistry. The importance of asymmetric hydrogenation was recognized by the 2001 Nobel Prize in Chemistry awarded to William Standish Knowles and Ryōji Noyori. Two major mechanisms have been proposed for catalytic hydrogenation with rhodium complexes: the unsaturated mechanism and the dihydride mechanism. While distinguishing between the two mechanisms is difficult, the difference between the two for asymmetric hydrogenation is relatively unimportant since both converge to a common intermediate before any stereochemical information is transferred to the product molecule. The preference for producing one enantiomer instead of another in these reactions is often explained in terms of steric interactions between the ligand and the prochiral substrate. Consideration of these interactions has led to the development of quadrant diagrams where 'blocked' areas are denoted with a shaded box, while 'open' areas are left unfilled. In the modeled reaction, large groups on an incoming olefin will tend to orient to fill the open areas of the diagram, while smaller groups will be directed to the blocked areas and hydrogen delivery will then occur to the back face of the olefin, fixing the stereochemistry. Note that only part of the chiral phosphine ligand is shown for the sake of clarity.