From monodentate to bidentate to monodentate with a trillion possibilities

摘要

The development of a chemical catalytic system, which is economically viable for the production of an unnatural amino acid (L-Dopa), in the late 1960's and early 70's was a major breakthrough in terms of enantioselectivity. The initial premise to substitute the triphenylphosphines of Wilkinson's catalyst with a chiral phosphines led to the discovery that PAMP gave a 50-60% ee of the reduced product but CAMP gave an improved 80-88% ee (Figure 1) (1). As the product can be crystallised to increase the enantioselectivity, the use of CAMP was good enough to consider an industrial process for the manufacture of L-Dopa that could compete with a resolution method (2). Kagan then found that DIOP provided about the same enantioselectivity as CAMP in the enamide reduction. This showed Knowles that his working hypothesis about the chirality needed to be very close to the metal was wrong. This led to Knowles two phosphines together, as in DIPAMP, and observing a dramatic increase the stereoselectivity of the reaction; DICAMP is not successful.