CHIRALITY MEDAL

Andreas Pfaltz - Winner of the 2016 Chirality Medal

Andreas PfaltzAndreas Pfaltz, Professor of Chemistry at the University of Basel, Switzerland, will receive the 2016 Chirality Medal and will present the Award Lecture at the „Chirality 2016“, the 28th International Symposium on Chirality (ISCD-28), on July 24th, 2016 in Heidelberg, Germany.

Prof. Pfaltz receives the honor for his seminal contributions to enantioselective catalysis.

Professor Pfaltz and his group have been active in the development of chiral ligands and metal catalysts for many years. Starting point was the development of the semicorrins in the mid 1980's. Key features of the semicorrin structure are a conformationally rigid C2-symmetric ligand scaffold, with two substituents in close proximity to the coordination sphere that have a strong and direct influence in a metal-catalyzed process.

The high enantioselectivities induced by semicorrins in copper-catalyzed cyclopropanation and cobalt-catalyzed conjugate reduction of a,b-unsaturated carboxylic esters and amides prompted the development of various structurally related ligands in the Pfaltz lab as well as in many other research groups. Bisoxazolines, now known as BOX ligands, have found an impressive number of applications in asymmetric catalysis and today are regarded as privileged ligands. The most recent addition to the bisoxazolines are the BoraBOX ligands, which have been successfully applied in several metal-catalyzed reactions.

 

C2-symmetric bidentate ligands play a very important role in asymmetric catalysis. Although C2-symmetry offers a number of advantages, for certain reactions non-symmetrical ligands with two different coordinating centers can allow more effective enantiocontrol than C2-symmetric ligands. Transition metal-catalyzed allylic substitution via symmetric allyl intermediates is an example. In this reaction, the regioselectivity of nucleophilic attack determines the ratio of the two enantiomeric products. If the metal center is coordinated by two electronically different heteroatoms, the allylic termini become electronically nonequivalent and thus are expected to display different reactivity. Therefore, non-symmetric ligands with two different coordinating atoms such as P and N could be highly effective. Indeed, palladium complexes with phosphinooxazolines (PHOX) ligands, developed independently in the groups of Pfaltz, Helmchen and J. M. J. Williams, turned out to be efficient enantioselective catalysts for palladium-catalyzed allylic substitutions. Because of their modular structure, a wide variety of ligands are available, as the oxazoline rings, phosphine groups and backbones can be varied in numerous ways using convenient starting materials such as amino acids. In this way the ligand structure can be sterically and electronically tuned for a specific application. Oxazoline-based P,N-ligands have an application range complementary to the P,P-ligands developed by the Trost group, have allowed to significantly enhance the scope of enantioselective allylic substitutions. Further studies have shown that PHOX and related P,N-ligands can induce high enantioselectivities in numerous other metal-catalyzed reactions, such as Heck reactions, 1,4-additions of organozinc reagents to enones, and Ag(I)-catalyzed [3+2] cycloadditions of azomethine ylides.

The PHOX type P,N-ligands have found their prime application in asymmetric hydrogenation, where they have led to a major breakthrough. Since the early 1970s, when Kagan pioneered hydrogenations using C2-symmetric ligands and the famous L-Dopa process was established by Knowles at Monsanto, hydrogenation has played a dominant role in applied asymmetric catalysis. Numerous chiral phosphine ligands are available today, which induce very high enantioselectivity in rhodium- and ruthenium-catalyzed hydrogenations of suitably functionalized olefins. However, the application range of Rh and Ru catalysts is limited, as they require the presence of a polar functional group next to the C=C bond that can coordinate to the metal center. With unfunctionalized olefins, these catalysts generally show low reactivity and unsatisfactory enantioselectivity. In the course of their work on catalysts containing PHOX ligands, Pfaltz, noting their resemblance to the Crabtree catalyst, [(Cy3P)(pyridine)Ir(COD)]PF6, introduced iridium complexes with chiral P,N-ligands that can overcome the limitations.

In contrast to Rh and Ru catalysts, the Ir-catalysts do not require a coordinating group next to the C=C bond. However, Initial experiments with cationic PHOX complexes were disappointing because of rapid catalyst deactivation. Only after the seminal importance of the counter ion was recognized, highly active catalysts were developed that allow hydrogenation of unfunctionalized tri- and even tetrasubstituted olefins. Thus, with BarF (tetrakis[3,5-bis(trifluoromethyl)-phenyl]borate) as counter anion TONs of >5000 could be achieved, whereas the corresponding hexafluorophosphate salts usually lost catalytic activity after 40-200 turnovers. An extensive search for other P,N-ligands led to a diverse set of new Ir complexes, which have considerably expanded the scope of enantioselective hydrogenation to many different classes of unfunctionalized as well as functionalized olefins. Stimulated by this work, the Pfaltz and several other research groups have reported additional oxazoline- and pyridine-derived P,N-ligands. High enantioselectivity, low catalyst loadings, essentially quantitative yields, and mild conditions are attractive features of these transformations.

 

For a long time, purely alkyl-substituted olefins could not be hydrogenated with satisfactory enantioselectivity. However, bicyclic pyridine-based ligands finally led to a breakthrough. The potential of these catalysts was demonstrated with the highly enantio- and diastereoselective introduction of the two stereocenters of the side chain of tocopherol (vitamin E) by simultaneous hydrogenation of three C=C bonds.

Another current project of the Pfaltz group is focused on the development of new screening methods for chiral catalysts. Parallel screening based product analysis has potential pitfalls, because catalytically active impurities or competing unselective background reactions can strongly affect the enantiomeric purity of the product. Such problems would be avoided if the catalyst's ability for enantiodiscrimination could be determined directly from examining catalyst-reactant intermediates rather than by product analysis. The feasibility of this concept was demonstrated for the palladium catalyzed kinetic resolution of allylic esters, using electrospray ionization mass spectrometry (ESIMS) as an analytical tool.

 

With this award, Andreas Pfaltz joins 26 other distinguished scientists who have received this prize since its institution in 1991 by the Societa Chimica Italiana.

Chirality Medal
The Chirality Medal was instituted by the Societa Chimica Italiana in 1991 to honor internationally recognized scientists who have made a distinguished contribution to all aspects of chirality. It is awarded each year by a Chirality Medal Honor Committee comprising the Chirality International Committee members and the most recent recipients of the medal.


Previous Chirality Medals have been awarded to the following scientists:

 

CONFERENCE YEAR

CHIRALITY MEDAL WINNER

1991

E. Gil-Av (Israel) and J. Jacques (France)

1992

V. Prelog (Switzerland)

1993

K. Mislow (USA)

1994

W. Pirkle (USA)

1995

K. Nakanishi (USA)

1996

E. L. Eliel (USA)

1997

R. Noyori (Japan)

1998

H. Kagan (France)

1999

V. Davankov (Russia)

2000

K. B. Sharpless (USA)

2001

Y. Okamoto (Japan)

2002

D. Seebach (Switzerland)

2003

D. W. Armstrong (USA)

2004

V. Schurig (Germany)

2005

K. Soai (Japan)

2006

M. Lahav (Israel)

2007

N. Berova (USA)

2008

W. Lindner (Austria)

2009

B. L. Feringa (The Netherlands)

2010

K. Mori (Japan)

2011

L. Barron (UK)

2012

E. Jacobsen (USA)

2013

E. Yashima (Japan)

2014

M.T. Reetz (Germany)

2015

C. Welch (USA)