CAMP and DIPAMP

During the late 1960s, Homer et al. [13] and Knowles and Sabacky [14] independently found that a chiral monodentate tertiary phosphine, in the presence of a rhodium complex, could provide enantioselective induction for a hydrogenation, although the amount of induction was small [15-20]. The chiral phosphine ligand replaced the triphenylphosphine in a Wilkinson-type catalyst [10, 21, 22]. At about this time, it was also found that [Rh(COD)2]+ or [Rh(NBD)2]+ could be used as catalyst precursors, without the need to perform ligand exchange reactions [23]. 

It is interesting to note that a few rales of thumb and myths came out of these early studies. Many of these have been perpetuated for decades, and the myths are only just being put to rest. Knowles showed that only two phosphorus ligands were needed on the metal to achieve reduction, and not three as in Wilkinson s catalyst [10]. The success of DIPAMP and DIOP led to the belief 

Another trend that arose from Knowles results was that a wide range of en-amides (dehydroamino acids) could be reduced to amino acids [22, 25, 27, 29]. 

This was in contrast to the enzymatic reactions known then, where enzymes were believed to be very substrate specific. As we now know, there is no general catalytic system to perform asymmetric hydrogenations and even within a small class of substrates, some ligand variation is required to achieve optimal results. 

The results obtained with the Knowles catalyst system have led to a number of useful tools that have helped with the development of other ligand families. 

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Another advantage of the sequence in Figs. 12 and 13 was that CAMP and DIPAMP were prepared from a common intermediate (10) and no new resolution procedure needed to be worked out. Thus, the change to an improved ligand could be done with minimum dislocation, both at the synthesis and the utilization end. It is a dear advantage of catalytic processes that it is often easy to shift from the old to the new. 

Shortly afterwards, we came up with our own chelating bisphosphane ligand, by dimerizing PAMP through another Mislow procedure. We called it DIPAMP, and chirality resided on the phosphorus atom. DIPAMP worked at about 95% ee in our L-dopa system and we quickly converted our commercial process to be able to use it. Part of our motivation to make a quick change was that DIPAMP was easier to make than CAMP, and, in addition, it was a nice, crystalline air-stable solid (Fig. 7). 

This achievement was unique in two respects 1) it was the first example of industrial application of a homogeneous enantioselective catalysis methodology and 2) it represented a rare example of very quick convergence of basic knowledge into commercial application. The monophosphine ligand CAMP was shortly replaced by the related diphosphine ligand DIPAMP which improved the selectivity for the I-DOPA system up to 95% ee [45]. 

The history of bidentates was preceded by some successes of monodentates, but these were soon overshadowed by DIPAMP. For instance Knowles reported first about the monodentate homologues of DIPAMP, which gave respectively 55% (PAMP) and 88% e.e. (CAMP) in the hydrogenation of 2-acetamidocinnamate [13,24] (Figure 4.21). Since 1999 a renaissance of monodentates has taken place. 

Efficient asymmetric hydrogenation of alkenes other than the amino acid and dipeptide precursors described above has met with only limited success. This appears to be at least in part due to the inability of many alkenes to function as bidentate chelates. Ethyl 2-acetoxyacrylate was hydrogenated with an enantiomer excess of 89% using [Rh(cod)(R,R-DIPAMP)]+, giving the S-enantiomer (equation 53). The ligands CHIRAPHOS, PROPHOS, DIOP, BPPM and CAMP were less effective.266... 

A common way to generate a chiral catalyst involves a modification of Wilkinson s catalyst (340) in which an optically active tertiary phosphine, bis- or tris-phosphines are used as ligands in place of triphenyl-phosphine. If the phosphorous atom of the added phosphine is the stereogenic center, the optical yields are usually 4-22%, as in the conversion of atropic acid (447) to hydratropic acid (448) with 22% ee." " " An example of this type of phosphine is (-)-methylpropylphenylphosphine. bis(Phosphines) are commonly used, including 449 (called dipamp)" " and 450 (called R-camp)." " ... 

When these catalysts react with rhodium salts, many intermediate metal complexes can be formed, including Rh(diphos)cod+, Rh(diphos)Ac, Rh(dipamp)2, Rh(diop)NBD", and Rh(camp)2COD+. In work by Halpern,... 

Rh(diPAMP)(A )], Ac = acylaminocinnamic acid, could be monitored and bond lengths determined. In the adduct there was clear evidence of coordination to both the C-C double bond and a carbonyl oxygen. Monitoring a similar sequence for derivatives of the chiral monodentate phosphine, CAMP, also provided evidence for the solvated analogue, [Rh(CAMP)2(MeOH)2) but attempts to fit the data In the presence of the catalyst substrate were unsuccessful, apparently indicating a mixture of solution species. 

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