I  U  P  A  C






News & Notices
.. Prize for Young Chemists
.... 2000 winners
.... 2001 winners

Organizations & People

Standing Committees

Divisions

Projects

Reports

Publications

Symposia

AMP

Links of Interest

Search the Site

Home Page

 

 

IUPAC Prize for Young Chemists - 2001
Honorable Mention

 

  Volker P.W. B�hm receives one of four Honorable Mention awards associated with the IUPAC Prize for Young Chemists, for his Ph.D. thesis work entitled "Catalytic Activation of Aryl Chlorides in Heck-Type Reactions"

Current address (at the time of application)

University of North Carolina at Chapel Hill
Venable and Kenan Laboratories CB#3290
Chapel Hill, NC 27599-3290, USA

Tel: +1 919 962-0363
Fax: +1 919 962-2476
E-mail: [email protected]

Academic degrees

  • Dr. rer. nat. (Ph.D.) in Chemistry; Technische Universit�t M�nchen, Germany; May 2000.
  • Diplom in Chemistry; Philipps-Universit�t Marburg, Germany; September 1997.
  • Vordiplom in Chemistry; Johannes Gutenberg-Universit�t Mainz, Germany; March 1994.

Ph.D. Thesis

Title Catalytic Activation of Aryl Chlorides in Heck-Type Reactions
Adviser Prof. Dr. Dr. h.c. mult. Wolfgang A. Herrmann
Thesis Committee Ivar Ugi, Institut f�r Organische Chemie und Biochemie, Technische Universit�t M�nchen; Wolfgang Beck, Lehrstuhl f�r Anorganische Chemie, Ludwig-Maximilians Universit�t M�nchen; Klaus K�hler, Institut f�r Anorganische Chemie, Technische Universit�t M�nchen.

Essay

Catalysis is of crucial importance for the development of environmentally benign synthetic processes. Especially homogeneous catalysis which combines aspects of organometallic chemistry and organic synthesis allows highly selective transformations at mild conditions. However, one of the major problems in homogeneous catalysis is the activation of strong carbon-heteroatom bonds in cheap and abundant starting materials. Therefore, the utilization of chloroarenes in the palladium-catalyzed Mizoroki-Heck vinylation (1) and related cross-coupling reactions (2) has been focused by catalyst development in recent years both from synthetic and fundamental points of view.[1]



At the beginning of this Ph.D. thesis, only rare examples of mostly activated chloroarenes were known to be reactive in transformations of type (1) or (2).[2] Broad application was hampered by either low stability of the catalyst or the demand of high catalyst loading. In order to develop catalyst systems which are capable of efficiently activating all types of chloroarenes at low catalyst loadings, three different approaches were used:

1) For the optimization of catalyst systems, the understanding of the reaction mechanism is of fundamental importance. As phospha-palladacycle 1 is an example for a highly active catalyst with bromoarenes, the Mizoroki-Heck vinylation (1) was carefully examined in order to determine the nature of the active species as well as the influence of salt additives.

The interest in catalyst 1 was also driven by a discussion in the literature about a possible, non-classical mechanism involving Palladium(IV)-intermediates. Data supporting and disproving this assumption had been presented in cause. In this Ph.D. thesis, hydrogen isotope effects, Hammett correlations and product distributions of catalyst 1 were compared to those of proposed intermediates in a potential classical mechanism. This revealed that the mechanism in case of catalyst 1 is related to classical proposals and that Palladium(IV)-intermediates are very unlikely.

Furthermore, the kinetic studies reveal that salt additives are responsible for a strong "special salt effect" induced by the anion and a moderate "normal salt effect" due to the increased polarity of the reaction medium. As a consequence, the reaction is best performed in salt melts, i.e. ionic liquids. The optimized reaction medium [NBu4]Br allows 1 and other frequently used catalysts, including highly desirable but least active ligand-free palladium salts like PdCl2, to perform substantially better. PdCl2 was previously only known to activate iodoarenes and can now be used to couple bromo and chloroarenes.

2) The first step in the catalytic cycles of the reactions (1) and (2) is the oxidative addition to palladium(0) complexes. Due to the reluctant activity of chloroarenes, we wanted to activate the catalysts for this reaction step. Lewis-basic, electron-donating ligands are known to promote oxidative additions.[3] A novel class of electron-donating ligands are N-heterocyclic carbenes 2 which have the advantage of forming extraordinarily strong metal-ligand bonds allowing the formation of highly defined catalyst structures including stable and recyclable immobilized catalysts as was shown in this thesis.

The first general synthetic route to homoleptic palladium(0) complexes bearing N-heterocyclic carbenes was developed within this thesis (reaction 3). In the Suzuki-Miyaura reaction (2), [M] = B(OH)2, the most active catalyst of this type achieves turnover-numbers and turnover-frequencies much higher than the best published phosphine-system.

 

By transfer of knowledge gained with palladium as the catalyst metal, highly active, homoleptic nickel(0) complexes of N-heterocyclic carbenes were developed which are extraordinarily active in the Kumada cross coupling reaction (2), [M] = MgCl. With the optimized catalysts, even the selective activation of fluoroarenes, which were until then considered to be unreactive in this type of reaction, could be transformed.

3) Combinatorial catalysis is a convenient means of screening a large amount of potential catalysts for their activity in a desired reaction. As an essential necessity for efficient screening, high-throughput must be achieved for (i) the synthesis of potential catalysts, (ii) the desired reaction under inert atmosphere, and (iii) the analysis of the reaction products.

For the first time, this thesis shows the use of N-heterocyclic carbenes 2 as ligands in screening assays to be possible. A modified synthesis route (4) of imidazolium salts as precursors to the N-heterocyclic carbenes was developed which allows the easy preparation of a large library of potential ligands. Taking advantage of the in situ formation of N-heterocyclic carbenes from imidazolium salts in the presence of a base, this library was combined with transition metal salts. New reaction vessels were designed to run the reactions under inert gas applying standard Schlenk-techniques. Novel screening assays based on 19F-NMR and color identification of the reaction products were developed and applied for the first time.

Highly active in situ catalyst systems consisting of an imidazolium and a nickel or palladium salt were discovered by these screening methods e.g. for the Kumada and the Negishi cross coupling reactions (2), [M] = MgCl, ZnCl. In comparison to the defined catalysts described above, these systems have the advantage of their components being easy to prepare and being less sensitive towards air and moisture.

 

In summary, within this thesis the activation of chloroarenes (and in one particular example even fluoroarenes) in Heck-type reactions (1) and (2) was achieved by novel catalysts and optimized reaction conditions: (i) Studying mechanistic details led to the optimization of the reaction conditions for the Mizoroki-Heck vinylation (1), (ii) the application of novel ligands favoring the first step in the catalytic cycles led to the discovery of novel, highly active catalysts for the reactions (2), and (iii) in situ systems, which are especially useful for organic synthesis in terms of handling, stability of the components as well as convenience of preparation, were optimized by high-throughput screening methods. In this thesis, no "magic" catalyst for all transformations was identified but different structures had to be optimized for each individual reaction owing to subtle differences in the rate determining steps of the catalytic cycles. Thus, both palladium and nickel complexes as well as phosphines and N-heterocyclic carbenes 2 as ligands were found to be most active in different reactions.

 

References:
[1] Applied Homogeneous Catalysis with Organometallic Compounds (Eds.: B. Cornils, W. A. Herrmann), Wiley-VCH, Weinheim, 1996.
[2] see references in: (a) T. H. Riermeier, A. Zapf, M. Beller, Top. Catal. 1998, 4, 301-309; (b) R. St�rmer, Angew. Chem. Int. Ed. 1999, 38, 3307-3308.
[3] V. V. Grushin, H. Alper, Chem. Rev. 1994, 94, 1047-1062.


Page last modified 23 April 2001.
Copyright ©2001 International Union of Pure and Applied Chemistry.
Questions or comments about IUPAC, please contact, the Secretariat.
Questions regarding the website, please contact Web Help.