New polynuclear catalysts for atom-transfer radical addition reactions

Homo- and heterobimetallic complexes of the late transitions metals have been synthesized by metathesis reactions of the corresponding chloro-bridged dimers. These reactions have the advantage of being fast and giving rise to structurally defined products in quantitative yield. Complexes with three chloro-bridges of the general formula [LM(μ-Cl)3RuLm] (LM = (arene)Ru, CpIr, or CpRh; RuLm = RuCl(PPh3)2 or RuCp*) were investigated in detail and several of these were structurally characterized. Evidence is provided that triply bridged complexes of this kind can undergo fast exchange reactions. The complexes with the fragment {RuCl(PPh3)2} were found to catalyze atom-transfer radical addition (ATRA) reactions. Structurally related complexes with chelating 1,4-bis(diphenylphosphino)butane (dppb) or 1,4-bis(dicyclohexylphosphino)butane (dcypb) ligands instead of the two PPh3 ligands could likewise be generated. A total of 69 different combinations were prepared and tested in a combinatorial fashion for their ability to catalyze the ATRA of CCl4 to styrene. Two combinations were found to be remarkably active and the corresponding complexes [CpRh(μ-Cl)3RuCl(PPh3)2] and [{(tpc)Rh(μ-Cl)3Ru(dcypb)}2(μ-N2)] were identified and structurally characterized. They proved to be among the most active catalysts described so far. Other ATRA catalysts were investigated. The cationic complex [CpRu(PPh3)2-(CH3CN)]OTf was found to display a higher stability than the related neutral catalyst [Cp*RuCl(PPh3)2]. Total TONs of up to 890 for the addition of CHCl3 to styrene were obtained at a temperature of only 40°C. For the first time, ATRA reactions are reported using a mixture of [(arene)RuCl2]2 and PCy3 as the catalyst precursors. As a product of the reaction between [(C6H3iPr3)-RuCl2]2 and PCy3, the tetranuclear complex [{(C6H3iPr3)Ru(μ-Cl)3RuCl(PCy3)}2(μ-N2)] was isolated, which itself proved to be highly active. When the arene and the N2 ligands of the latter were exchanged for a cymene ligand and an ethylene ligand, respectively, the resulting binuclear complex [(cymene)Ru(μ-Cl)3RuCl(PCy3)(η2-C2H4)] was obtained. It proved to be even more efficient than the dinitrogen complex and allowed the Kharasch addition of CCl4 to 1-olefins to be carried out at a temperature as low as 0°C. The observed TOFs (1100 h-1 at 24°C and 1550 h-1 at 40°C) are comparable to those reported for the most active catalysts.

Chiral Cyclopentadienyls: Enabling Ligands for Asymmetric Rh(III)-Catalyzed C-H Functionalizations

Nicolai Cramer, Baihua Ye

Transition-metal catalyzed C-H functionalizations became a complementary and efficient bond-forming strategy over the past decade. In this respect, Cp*Rh(III) complexes have emerged as powerful catalysts for a broad spectrum of reactions giving access to synthetically versatile building blocks. Despite their high potential, the corresponding catalytic enantioselective transformations largely lag behind. The targeted transformations require all the remaining three coordination sites of the central rhodium atom of the catalyst. In consequence, the chiral information on a competent catalyst can only by stored in the cyclopentadienyl unit. The lack of suitable enabling chiral cyclopentadienyl (Cp-x) ligands is the key hurdle preventing the development of such asymmetric versions. In this respect, an efficient set of chiral Cp-x ligands useable with a broad variety of different transition-metals can unlock substantial application potential. This Account provides a description of our developments of two complementary classes of C-2-symmetric Cp-x derivatives. We have introduced a side- and back-wall concept to enforce chirality transfer onto the central metal atom. The first generation consists of a fused cyclohexane unit having pseudo axial methyl groups as chiral selectors and a rigidifying acetal moiety. The second ligand generation derives from an atrop-chiral biaryl-backbone and which possesses adjustable substituents at its 3,3'-positions. Both ligand families can be modulated in their respective steric bulk to adjust for the specific needs of the targeted application. The cyclopentadienes can be metalated under standard conditions. The corresponding chiral rhodium(I) ethylene complexes are relatively air and moisture and represent storable stable precatalysts for the targeted asymmetric Rh(III)-catalyzed C-H functionalizations. These complexes are then conveniently oxidized in situ by dibenzoyl peroxide to give the reactive (CpRh)-Rh-x(III)(OBz)(2) species. For instance, this catalyst is used for directed C-H activations of aryl hydroxamates and the subsequent enantioselective trapping with olefins, providing dihydroisoquinolones in very high enantioselectivities. In addition, we have established highly selective intramolecular trapping reactions with tethered higher substituted alkenes giving dihydrobenzofurans with quaternary stereogenic centers. Concerning intermolecular reactions, allene coupling partners allow for an enantioselective hydroarylation yielding substituted allylated compounds. A trapping process of the cyclometalated intermediate with diazo reactants enables the enantioselective construction of isoindolinones. Moreover, the catalysts can be used for the construction of atropchiral biaryl motives using a dehydrogenative Heck-type reaction. The development of flexibly adjustable chiral Cp-x ligands is described in this Account showcasing their applicability for a variety of Rh(III) catalyzed CH functionalization reactions. These Cp-x derivatives hold promise as powerful steering ligands for further transition-metals used in asymmetric catalysis.

American Chemical Society2015

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

Rh(III)-Catalyzed C-H Functionalizations as Strategies for Versatile Organic Building Blocks

Van Manh Pham

Transition-metal catalyzed C-H functionalizations have impacted and changed synthetic approaches towards the construction of relevant complex molecules, comprising natural products, active pharmaceutical ingredients, and organic materials. This thesis describes the development of Rh(III)-catalyzed reactions via directed C-H functionalization and non-directed C-H functionalization. In this respect, acylated sulfonamides and N-sulfonyl ketimines were successfully employed as suitable directing groups, enabling directed C-H bond activation in the presence of a rhodium(III) catalyst. Subsequent migratory insertion of internal alkynes delivered a rich array of versatile benzosultams and chiral spirocyclic sultams, both of which are relevant structures in medicinal chemistry. Notably, the use of rhodium(III) complexes equipped with a suitable atropchiral cyclopentadienyl ligand enables enantioselective and high yielding access to the challenging spirocyclic sultam scaffolds. Complementary to the directed C-H bond functionalizations, application of CpRh(III) complexes in non-directed C-H functionalization reactions have been disclosed. Specific applications of this challenging strategy include the synthesis of highly valuable polyarenes from completely unbiased arenes via double C-H activation, and subsequent addition of internal alkynes. This method provides a convenient handle to access highly substituted and highly soluble acenes, possessing valuable electronic and photo physical properties. Furthermore, non-directed C-H functionalization of electron-rich heterocycles was also developed. In this context, a CpRh(III) catalyst enables a C2-selective activation of heteroarenes. Upon addition across an alkyne, a transmetalation to Cu(II) allows reductive C-O bond formation to deliver tetrasubstituted enol esters in a trans-selective fashion. A three-component coupling of heteroarenes, alkynes, and carboxylic acids was successfully demonstrated.

EPFL2016