Los Alamos National Laboratory

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LANL researchers shine more light on the mechanism of one of the most efficient artificial catalytic reactions developed to date

In a review article published April 20th, 2016 and featured on the cover of the chemistry journal Dalton Transactions, Los Alamos researchers discuss new discoveries about the mechanisms of the Noyroi catalyst. This catalyst as become key to many industrial reactions since its discovery in 1995, making its function of great interest to chemists across the world.

Catalytic hydrogenations represent the largest-volume human-made chemical reactionsin the world.1 Many industrially important processes are based on a homogeneous version of this reaction. Homogeneous catalysis affords a number of convenient properties including mild reaction conditions, low cost, operational simplicity, high activities & selectivities that can be tuned via electronic and steric effects of the ligand, ease of catalyst structure determination and reaction mechanism analysis that can also be readily probed.

Among three functional groups (C=C, C=O, C=N), special attention is given to the hydrogenation of carbonyl groups2 with ketones being among the most common unsaturated substrates containing this fragment.3 After the discovery of Noyori’s molecular catalyst in 1995 (Figure 1, Nobel Prize 2001), the asymmetric hydrogenation of prochiral ketones with M/NH bifunctional catalysts has become one of the most efficient artificial catalytic reactions developed to date (enantiomeric excesses up to 99.9%, catalyst loadings of ~10-5mol %), the efficacy of which has closely approached to that of natural enzymatic systems. The process has become a practically realized and key technology for small- up to industrial-scale production of optically active compounds, including medicines, agrochemicals, and perfumes.The mechanism of this reaction has attracted a great deal of attention from different research groups worldwide. Over the past 15 years, Noyori’s catalyst (and other so-called bifunctional ones) was considered to reduce carbonyl substrates via a so-called non-classical metal–ligand bifunctional mechanism which is based on the concept of metal–ligand cooperation. The latter implies that both the metal and the ligand participate in the bond cleavage/formation events via their chemical modification. It was recently shown by LANL scientists that the reaction is much more sophisticated in reality and that Noyori’s catalyst indeed may operate via a completely different reaction mechanism.4 More details are discussed in their recent invited review article (Pavel A. Dub and John C. Gordon, C-IIAC).5

A reviewer’s comment on the paper is shown below:
“This perspective presents a comprehensive analysis of the recent advances, mainly coming from authors’ research, regarding the understanding of the mechanism of homogenous ketone hydrogenation by Noyori’s type catalysts. A series of groundbreaking papers from the authors have changed well established paradigms for this important reaction and, in a more general way, for the nowadays well accepted concept of metal-ligand bifunctional catalysis. In particular, accurate computational studies have given evidence that neither the mechanism is a concerted hydride/proton transfer nor necessarily the proton must come from the N-H ligand. These results are summarised, in a very educational manner, in this perspective. The paper begins with an illustrative critical overview of the experimental and computational techniques used in mechanistic studies of the reaction, and ends us with an updated and overwhelming references section.”

REFERENCES

  1. Kubas, G. J. Chem. Rev. 2007, 107, 4152.
  2. Magano, J.; Dunetz, J. R. Org. Process Res. Dev. 2012, 16, 1156.
  3. Noyori, R.; Ohkuma, T. Angew. Chem., Int. Ed. 2001, 40, 40.
  4. (a) P. A. Dub, N. J. Henson, R. L. Martin and J. C. Gordon, J. Am. Chem. Soc., 2014, 136, 3505; (b) P. A. Dub and T. Ikariya, J. Am. Chem. Soc., 2013, 135, 2604.

P. A. Dub, J. C. Gordon Dalton Trans.,invited review, Advance Article, appeared online 21st March, 2016; DOI: 10.1039/C6DT00476H, and references therein.

Figure 1. Recent research described by Dub and Gordon sheds light on how the industrially important Noyori catalyst operates.

Figure 1. Recent research described by Dub and Gordon sheds light on how the industrially important Noyori catalyst operates.

Figure 2. Artist’s conception of the conversion of starting material to a wide range of products.

Figure 2. Artist’s conception of the conversion of starting material to a wide range of products.

3/9/16


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