Novel Approaches for Ruthenium Catalyzed Atom Transfer Radical Addition Reactions

A new catalytic procedure for atom-transfer radical addition (ATRA) and cyclization (ATRC) reactions is described. The combination of the ruthenium(III) complex [RuCl2Cp*(PPh3)] with magnesium allows these reactions to be performed under mild conditions with high efficiency. It is suggested that magnesium acts as a reducing agent that generates and regenerates the catalytically active ruthenium(II) species. With magnesium as the co-catalyst, various dinuclear ruthenium ethylene and β-diketiminato-ruthenium complexes were tested in ATRA and ATRC reactions. It was found that these complexes in combination with Mg are potent catalysts. Furthermore, the catalytic activity of [CpOsBr2(PPh3)] in conjunction with Mg as the co-catalyst has been evaluated. The Os complex allowed to perform the reactions with similar efficiency as the analogous Ru complex [CpRuCl2(PPh3)]. A novel method for the synthesis of substituted cyclopropanes is described. Olefins are reacted with 1,1'-dichlorides in a Ru-catalyzed atom transfer radical addition process and the resulting 1,3-dichlorides are directly converted into cyclopropanes by reductive coupling with magnesium. This one-pot reaction is applicable to a variety of substrates and can be performed in an inter – or intramolecular fashion. A sequential intermolecular ATRA reaction is reported. By using an excess of the olefin, the ATRA mono adduct can be directly coupled with a second equivalent of olefin to give 1,5-dichlorides. These "double Kharasch" products can be employed in a following dechlorination step to give substituted cyclopentanes. The possibility of performing ATRA reactions in an enantioselective fashion was explored. Ruthenium complexes with different P-chiral phoshines or phosphoramidites were tested for selectivity in combination with magnesium.

Atom-Transfer Radical Addition Reactions Catalyzed by RuCp* Complexes: A Mechanistic Study

Gregor Kiefer, Katarzyna Pierzchala, Kay Severin, Andrzej Sienkiewicz, Katrin Anne Thommes

Kinetic and spectroscopic analyses were performed to gain information about the mechanism of atom-transfer radical reactions catalyzed by the complexes [RuCl2Cp*(PPh3)] and [RuClCp*(PPh3)2] (Cp*=pentamethylcyclopentadienyl), in the presence and in the absence of the reducing agent magnesium. The reactions of styrene with ethyl trichloroacetate, ethyl dichloroacetate, or dichloroacetonitrile were used as test reactions. The results show that for substrates with high intrinsic reactivity, such as ethyl trichloroacetate, the oxidation state of the catalyst in the resting state is +3, and that the reaction is zero-order with respect to the halogenated compound. Furthermore, the kinetic data suggest that the metal catalyst is not directly involved in the rate- limiting step of the reaction.

2009

Novel Applications of Nitrous Oxide and Transition Metals for C-C and C-N Bond Formation

Gregor Kiefer

This thesis describes novel methods for and investigations into C–C and C–N bond formation reactions. Chapter 1 gives a very brief overview of established strategies for the formation of new C–C bonds in organic synthesis. In chapter 2, a multi‐step one‐pot synthesis is described. Arylalkynes and ethylene are converted to 2‐arylbutadienes by ruthenium catalyzed enyne metathesis. Upon addition of polyhalogenated substrates, the butadienes react in a 1,4‐atom transfer radical addition (ATRA) to yield 1,5‐dichloropen‐2‐enes. These form substituted vinylcyclopropanes via reductive 1,5 dechlorination with magnesium or manganese. Chapter 3 describes a study about two complex organometallic structures that form by reaction of rhodium(III) chloride with tert‐butylacetylene. The reaction products demonstrate the ability of rhodium to mediate various reactions of alkynes such as [2+2+1] cycloadditions, oxidative cleavages and others. Cobalt‐catalyzed reactions for C–C bond formation are reported in chapter 4. In the first part, the focus lies on the putative pre‐catalysts [CoX2(dppe)] (X = Cl, Br, I; dppe = diphenylphosphinoethane), which are used together with a reducing agent (e. g. zinc) in a wide range of C–C bond formation reactions. It is shown that they are, in reality, complex salts of the formula [CoX(dppe)2]2[X3Co(dppe)CoX3]. The second part describes the synthesis and characterization of the complexes [CoX(dppe)(PPh3)] and [CoX(dppe)(η4‐isoprene)]. Without addition of a reducing agent, these cobalt(I) complexes catalyze reactions that are usually accomplished with the catalyst system Co(II)/dppe/Zn. These results provide evidence that the active species in these reactions are indeed Co(I) complexes as supposed. In the fifth chapter, two methods for the use of nitrous oxide (N2O, laughing gas) in organic reactions are described. The challenge of using N2O in synthetic chemistry is to overcome its kinetic inertness. In the oxidative homo‐ and cross‐coupling of Grignard reagents, N2O takes the role of an oxidizing agent. The reactions proceed under mild conditions with copper, iron and cobalt salts as catalysts and exhibit high turnover numbers. The utilization of N2O has advantages compared to established methods with other oxidation agents such as oxygen. Furthermore, a procedure for the synthesis of triazenes from lithium dialkylamides, N2O and Grignard reagents is described. This method enables the synthesis of aryl and alkyl triazenes, but also alkenyl and alkynyl triazenes that are difficult to access via established procedures. Some alkynyl triazenes are selectively cytotoxic against certain cancer cell lines.

EPFL2015

Sequential ATRA-Reductive Cyclopropanation Reactions with a Ruthenium Catalyst in the Presence of Manganese

Charlotte Buron, Kay Severin

Atom-transfer radical addition (ATRA) reactions of ethyl trichloroacetate, dichloromalononitrile, or diethyl 2,2-dichloromalonate with olefins followed by dechlorination have provided functionalized cyclopropanes in one step. The RuIII complex [Cp*RuCl2(PPh3)] was used as a catalyst precursor and commercial Mn powder as reducing agent. Reactions with the less activated substrate ethyl dichloroacetate gave ATRA products with high turnover numbers but cyclopropanation was not observed.

Wiley-Blackwell2011

Novel Applications of Nitrous Oxide and Transition Metals for C-C and C-N Bond Formation

Gregor Kiefer

EPFL2015