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C–H activation through late transition metal cyclometallation. Addressing selectivity and reactivity problems.

Kondrashov, Mikhail LU (2015) In Metal controlled regioselectivity in the cyclometallation of 2-(1-naphthyl)-pyridine, Kondrashov, M.; Raman, S., Wendt, O. F. Chem Commun. 2015, 51, 911–913.
Abstract (Swedish)
Popular Abstract in English

Synthetic chemicals are the basis of the modern civilisation. Nowadays, they have a bad reputation, but it is only due to them that we are able to live healthier, longer, receive improving medical treatments, use the comforts of modern technologies and not die of thirst and starvation, despite the immense population growth. The main task of organic synthesis is to transform molecules into other molecules. Since molecules consist of atoms bound to each other, transforming one molecule into another molecule is essentially a question of breaking some of the existing bonds and making new ones.

One typical recurrent problem in synthesis is breaking C—H bonds. Most of our organic chemical... (More)
Popular Abstract in English

Synthetic chemicals are the basis of the modern civilisation. Nowadays, they have a bad reputation, but it is only due to them that we are able to live healthier, longer, receive improving medical treatments, use the comforts of modern technologies and not die of thirst and starvation, despite the immense population growth. The main task of organic synthesis is to transform molecules into other molecules. Since molecules consist of atoms bound to each other, transforming one molecule into another molecule is essentially a question of breaking some of the existing bonds and making new ones.

One typical recurrent problem in synthesis is breaking C—H bonds. Most of our organic chemical feedstock consists of hydrocarbons (molecules that have only carbon and hydrogen atoms in them). This very special chemical composition makes these molecules suitable for a limited amount of applications. The majority of chemicals we need require nitrogen, oxygen, phosphorus, sulfur, halogens and other elements to be present in the molecule in order to have the required properties. Hence, we need to break C—C and C—H bonds and make new ones to get the molecules we want. At this point we stumble at a problem: not only is a C—H bond, typically, a very strong bond, but it is also fairly unpolar, which makes it difficult for this bond to undergo many interactions. Also, large organic molecules usually contain many C—H bonds, which can have fairly similar properties and only some of them should be broken to produce a certain target molecule. During the past decades metal-catalysed C—H bond activation has emerged as a huge field of research, providing numerous new methods for cheap and facile transformation of C—H bonds into other bonds.

The current work is dedicated to some of the auxiliary problems existing in this field. In order to progress faster in the creation of new methods, we need to know more about the properties of the metal catalysts and their interaction with C—H bonds. In this thesis I was able to study the behaviour of different metal catalysts towards a specific substrate, which could point out the difference between their properties. My attempt to expand the scope of catalysts and reagents used in C—H activation reactions was unsuccessful, but it indicated important specifics of the properties of relevant catalysts. At last, I was able to study an old, well-known reaction and show that it can proceed under completely unexpected conditions, resulting in a C—H activation at one of the lowest temperatures registered. (Less)
Abstract
The ligand-directed C—H activation relies on a coordinating donor atom being in proximity to the C—H bond activated. Cyclometallation of 2-(1-naphthyl)-pyridine – a substrate containing both γ- and δ-positions in proximity to the directing nitrogen atom – was studied. Cycloruthenation and cyclopalladation result in γ-substitution and formation of the corresponding 5-membered metallacycles, which is in agreement with published regioselectivities of the corresponding catalytic reactions. Simultaneously, cycloauration and cycloborylation result in δ-substitution and formation of the corresponding 6-membered metallacycles. X-ray structures of all the metallacycles are presented. Deuterium labelling studies show that the cyclopalladation and... (More)
The ligand-directed C—H activation relies on a coordinating donor atom being in proximity to the C—H bond activated. Cyclometallation of 2-(1-naphthyl)-pyridine – a substrate containing both γ- and δ-positions in proximity to the directing nitrogen atom – was studied. Cycloruthenation and cyclopalladation result in γ-substitution and formation of the corresponding 5-membered metallacycles, which is in agreement with published regioselectivities of the corresponding catalytic reactions. Simultaneously, cycloauration and cycloborylation result in δ-substitution and formation of the corresponding 6-membered metallacycles. X-ray structures of all the metallacycles are presented. Deuterium labelling studies show that the cyclopalladation and cycloauration are irreversible, while the cycloruthenation is reversible and happens in both γ- and δ-positions.

Attempts to synthesise bimetallic palladium complexes, consisting of two (2-phenyl-pyridine) palladium fragments connected via bridging ligands, resulted predominantly in the formation of monometallic species. While 1,8-naphthyridine and 7-aza-indole bind to palladium in an L-fashion with only one of the two nitrogen atoms, N-piperidine dithiocarbamic acid binds with both sulfur atoms in a chelating, rather than a bridging fashion. 3,3-Dimethylglutaric acid acts as a bridging ligand. X-ray structures of naphthyridine and dithiocarbamate complexes are presented. No increase in the reactivity is observed, when 1,8-naphthyridine, 7-aza-indole and N-piperidine dithiocarbamic acid were used as additives in palladium-catalysed acetoxylation and bromination of 2-phenyl-pyridine.

Oxidative anion metathesis was employed as a method of synthesis of organic salts. Trimethylsulfoxonium iodide salts can be converted to tetrafluoroborate, hexafluorophosphate, trifluoroacetate, tosylate and bis-triflimide salts in the presence of hydrogen peroxide and the corresponding acids. The scope of cations, suitable for this reaction also includes N-alkylpyridinium and quaternary phosphonium salts.

N-acetoxypyridinium chloride was employed as an oxidant in the palladium-catalysed C—H functionalisation of 2-aryl-pyridine resulting in the formation of the corresponding chloro-derivative. Trimethylsulfoxonium tetrafluoroborate, hexafluorophosphate and tosylate are unreactive as oxidants towards 2-(phenyl)-pyridine palladium acetate.

Cyclopalladation of PCP pincer ligands with aromatic and aliphatic backbones by (PhCN)2PdCl2 was shown to proceed at temperatures as low as -62⁰C. The initial interaction results in the formation of a mixture of coordinated species, only some of which react further to form metallacyclic pincer compounds. The formation of pre-cyclometallation intermediates is kinetically disfavoured. However, C—H activation is fast and not rate-limiting in case of neither sp2 nor sp3 C—H bonds. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Prof. Tilset, Mats, University of Oslo, Norway
organization
publishing date
type
Thesis
publication status
published
subject
keywords
C—H activation, cyclometallation, pincer ligands, anion exchange, bimetallic complexes, oxidative functionalisation
in
Metal controlled regioselectivity in the cyclometallation of 2-(1-naphthyl)-pyridine, Kondrashov, M.; Raman, S., Wendt, O. F. Chem Commun. 2015, 51, 911–913.
pages
79 pages
publisher
Department of Chemistry, Lund University
defense location
Kemicentrum, Sal B
defense date
2015-12-04 13:15
ISBN
978-91-7422-418-4
language
English
LU publication?
yes
id
fa4a6d82-f5da-4606-ad82-069bbf3fa02d (old id 8165585)
date added to LUP
2015-11-12 14:31:22
date last changed
2016-09-19 08:45:14
@misc{fa4a6d82-f5da-4606-ad82-069bbf3fa02d,
  abstract     = {The ligand-directed C—H activation relies on a coordinating donor atom being in proximity to the C—H bond activated. Cyclometallation of 2-(1-naphthyl)-pyridine – a substrate containing both γ- and δ-positions in proximity to the directing nitrogen atom – was studied. Cycloruthenation and cyclopalladation result in γ-substitution and formation of the corresponding 5-membered metallacycles, which is in agreement with published regioselectivities of the corresponding catalytic reactions. Simultaneously, cycloauration and cycloborylation result in δ-substitution and formation of the corresponding 6-membered metallacycles. X-ray structures of all the metallacycles are presented. Deuterium labelling studies show that the cyclopalladation and cycloauration are irreversible, while the cycloruthenation is reversible and happens in both γ- and δ-positions.<br/><br>
Attempts to synthesise bimetallic palladium complexes, consisting of two (2-phenyl-pyridine) palladium fragments connected via bridging ligands, resulted predominantly in the formation of monometallic species. While 1,8-naphthyridine and 7-aza-indole bind to palladium in an L-fashion with only one of the two nitrogen atoms, N-piperidine dithiocarbamic acid binds with both sulfur atoms in a chelating, rather than a bridging fashion. 3,3-Dimethylglutaric acid acts as a bridging ligand. X-ray structures of naphthyridine and dithiocarbamate complexes are presented. No increase in the reactivity is observed, when 1,8-naphthyridine, 7-aza-indole and N-piperidine dithiocarbamic acid were used as additives in palladium-catalysed acetoxylation and bromination of 2-phenyl-pyridine.<br/><br>
Oxidative anion metathesis was employed as a method of synthesis of organic salts. Trimethylsulfoxonium iodide salts can be converted to tetrafluoroborate, hexafluorophosphate, trifluoroacetate, tosylate and bis-triflimide salts in the presence of hydrogen peroxide and the corresponding acids. The scope of cations, suitable for this reaction also includes N-alkylpyridinium and quaternary phosphonium salts.<br/><br>
N-acetoxypyridinium chloride was employed as an oxidant in the palladium-catalysed C—H functionalisation of 2-aryl-pyridine resulting in the formation of the corresponding chloro-derivative. Trimethylsulfoxonium tetrafluoroborate, hexafluorophosphate and tosylate are unreactive as oxidants towards 2-(phenyl)-pyridine palladium acetate.<br/><br>
Cyclopalladation of PCP pincer ligands with aromatic and aliphatic backbones by (PhCN)2PdCl2 was shown to proceed at temperatures as low as -62⁰C. The initial interaction results in the formation of a mixture of coordinated species, only some of which react further to form metallacyclic pincer compounds. The formation of pre-cyclometallation intermediates is kinetically disfavoured. However, C—H activation is fast and not rate-limiting in case of neither sp2 nor sp3 C—H bonds.},
  author       = {Kondrashov, Mikhail},
  isbn         = {978-91-7422-418-4},
  keyword      = {C—H activation,cyclometallation,pincer ligands,anion exchange,bimetallic complexes,oxidative functionalisation},
  language     = {eng},
  pages        = {79},
  publisher    = {ARRAY(0x86ddb08)},
  series       = {Metal controlled regioselectivity in the cyclometallation of 2-(1-naphthyl)-pyridine, Kondrashov, M.; Raman, S., Wendt, O. F. Chem Commun. 2015, 51, 911–913.},
  title        = {C–H activation through late transition metal cyclometallation. Addressing selectivity and reactivity problems.},
  year         = {2015},
}