Catalytic asymmetric hydrogenation

Abstract

Catalytic asymmetric hydrogenations have been reported using soluble complexes of rhodium and chiral phosphines. 1-5 These results suggest that any prochiral olefin or other unsaturated group that will hydrogenate with these soluble systems can be reacted to produce a predominance of one enantiomer when an optically active ligand is used. Then, the problem of achieving high efficiency becomes a purely synthetic one and is limited only by the ingenuity and skill of the chemist to make the proper ligand.We report the successful application of this principle for the preparation of optically active N-acyl-a-amino acids. Using phosphine ligands in which the phosphorus possesses asymmetry, we have been able to proceed from an initial lead of 1 5 2 5 % optical bias to 85-90% in a rational manner. The net result is a directed synthesis of chiral a-amino acids that, similar to enzymatic processes, do not require the usual resolution step.Our initial success reducing a-phenylacrylic acid with the known methylpropylphenylphosphine" as a complexing ligand gave an optical bias up to 28%.? This result encouraged us to use more complex systems, and we found that a-acylamidocinnamic acids reduced more readily with the same catalyst. A variety of tertiary phosphines gave efficiencies in the 28-32% range, as shown in TABLE 1.These results, though too low to be of practical use, did indicate that the asymmetric phosphine was integral to the catalytic process. However, we felt that further exchanging of R groups with other hydrocarbon radicals to increase

Pioneering Perspectives on Asymmetric Hydrogenation

“…4 Within a relatively short period, the first efficient chiral ligand, CAMP, was discovered, giving an 80% enantiomeric excess (ee) on dehydroamino acids. 5 This modest result, fortunately coupled with easy separations, enabled the commercial production of the anti-Parkinsonian drug L-DOPA at Monsanto, where AH was the key step. 1 The field really got underway with the discovery of C 2 -chiral DIOP by Dang and Kagan, 6 followed by Monsanto's improved C 2 bisphosphine Di-PAMP.…”

Asymmetric autocatalysis: Novel structures, novel mechanism?

“…Examples of effective asymmetric induction for almost all of the common catalytic processes of organic synthesis are on hand. Only recently has the predominance of chelating ligands been challenged by carefully designed unidentate ligands (2,3), redeveloping an early strand (4), but this work does not seriously undermine the effectiveness of basic principles of chelate catalyst synthesis. These principles are as follows.…”

Asymmetric Catalytic Synthesis of Organic Compounds using Metal Complexes in Supercritical Fluids

“…The first chiral catalytic reactions giving high enantiomeric excess were described by Knowles for the enantioselective hydrogenation of a-amidocinammic acids as part of a route to the anti-Parkinsons disease drug, l-DOPA (l-dihydroxyphenylalanine). [1] Knowles was awarded the Nobel Prize for this work, along with other pioneers of asymmetric catalysis, Sharpless and Noyori, in 2001.…”