Reactivity and fluxionality of late transition metal cluster compounds

The first part of this work deals with oxidative addition reactions of the triangulo platinum cluster [Pt3(μ-CO)3(PCy3)3]. Reactions with the electrophilic molecules ICH2CN and X2 (X = I and Br) and with the weakly polar reagent Ph3SnH have been studied. All three reactants convert the starting cluster firstly to novel 44-electron clusters probably via a SN2 mechanism. In the case of ICH2CN the adduct [Pt3(μ-CO)3(PCy3)3(I)(CH2CN)] is the first example where a Pt(II)L3 moiety is bonded to two Pt(0)L units via direct metal-metal bonds. A similar adduct was observed in the oxidative addition of Ph3SnH to the starting cluster, e.g. [Pt3(SnPh3)(μ-CO)3(PCy3)3H] which is the first reported neutral hydrido Pt-Sn cluster. With elementary halogens oxidative addition is followed by nucleophilic substitution of a CO ligand giving adducts [Pt3X(μ-CO)2(μ-X)(PCy3)3] (X = I, Br). Excess of reactants led to fragmentation of these adducts giving Pt(I) dimers and Pt(II) monomers. The observed trends in the nuclear spin-spin coupling constants in Pt(I) dimers have been reproduced by computation at the DFT level. The second part reports novel synthetic routes for pentanuclear platinum cluster compounds starting from trinuclear ones. The first complete NMR characterization of these Pt5 phosphino-carbonyl clusters was achieved as well. The final part of our work deals with CO scrambling processes in tetranuclear iridium and rhodium carbonyl clusters as studied by variable pressure NMR. The two major processes are the 'merry-go-round' and the 'change of basal face' which may be distinguished by the sign of the activation volume, negative for the former, positive for the latter process. On the basis of a theoretical study at the DFT level, transition state structures of the 'change of basal face' were proposed in the case of Ir2Rh2(CO)12 and Ir4(μ-SO2)(CO)11. These transition state structures have larger molecular volumes compared to those of ground state geometries in accordance with the experimentally determined, positive values of activation volume for this fluxional process.

Ring-Opening Reactions of Aminocyclopropanes and Aminocyclobutanes

Mingming Wang

Nitrogen-containing compounds are an important class of molecules in medicinal chemistry, chemical biology, biochemistry, material sciences or environmental sciences. Organic nitrogen occurs in many forms, ranging from small building blocks such as urea, amino acids, nucleotides, to complex natural products, drug molecules, proteins, nucleic acids, among others. The transformation of easily-accessed nitrogen-containing building blocks into more complex nitrogen-containing structures is therefore important for the synthesis of bioactive compounds or functional materials. Interested in donor-acceptor aminocyclopropanes and aminocyclobutanes, we first developed a Lewis-acid catalyzed formal [4+1] cycloaddition of donor-acceptor aminocyclobutanes with isocyanides, which resulted in the formation of cyclopentene-1,2-diamines. We then attempted to develop a formal [3+2] cycloaddition of donor-acceptor aminocyclopropanes with electron-deficient alkenes, which was mechanistically inspired by the Morita-Baylis-Hillman reaction. Apart from the donor-acceptor system, we were also attracted by simple aminocyclopropanes without electron-withdrawing group at vicinal position. We anticipated that the incorporation of cyclopropylamine into carboxylic-containing compounds followed by ring opening functionalization reactions could be used for the synthesis of more complex products. Therefore, we first disclosed an oxidative ring-opening strategy to transform acyl, sulfonyl or carbamate protected aminocyclopropanes into 1,3-dielectrophilic carbon intermediates bearing a halide atom (Br, I) and a N,O-acetal. Replacing the alkoxy group of the N,O-acetal was achieved under acidic conditions via an elimination-addition pathway, while substitution of the halides by nucleophiles was done under basic conditions via a SN2 pathway, generating a wide range of 1,3-difunctionalized propylamines. Based on the transformation described above, we further discovered an efficient synthesis of 4-amino thiochromans starting from simple aminocyclopropanes and thiophenols through a formal [3+3] annulation reaction. Next, we developed an oxidative ring-opening strategy to transform cyclopropylamides and cyclobutylamides into fluorinated imines. The imines can be isolated in their more stable hemiaminal form, with the fluorine atom installed selectively at the terminal position. Both cheap benzophenone with UV A light or organic and inorganic dyes with blue light could be used as photoredox catalysts to promote this process. Various fluorinated amines were then obtained by nucleophilic attack on the hemiaminals in one pot, giving access to a broad range of useful building blocks for medicinal chemistry. Finally, we turned our attention to the synthesis of diamines, which are essential building blocks for the synthesis of agrochemicals, drugs and organic materials, yet their synthesis remains challenging, as both nitrogen moieties need to be differentiated and diverse substitution patterns (1,2-, 1,3 or 1,4) are required. We described a new strategy giving access to 1,2-, 1,3- and 1,4- amido azides as orthogonally protected diamines based on the nitrogen-directed diazidation of alkenes, cyclopropanes and cyclobutanes.Other unsuccessful efforts over the last four years have also been described, together with some preliminary results of ring-opening cyanation and arylation reactions.

EPFL2022

Rh-catalyzed C-H Bond Heteroarylation with Hypervalent Iodine Reagents and Pd-Catalyzed Tethered Functionalizations of Carbon-Carbon Multiple Bonds.

Ashis Kumar Das

Transition metal-catalyzed C-H activation is a powerful tool for the synthesis of organic building blocks, materials, and natural products. Over the last decade, directing-group-assisted metal-catalyzed C-H functionalization has attracted increasing interest as a means to target specific C-H bonds. Moreover, a large variety of electrophiles has been employed in this kind of processes. In this thesis, we describe a novel C-6 selective C-H heteroarylation of pyridine-2-ones using indoleBX reagents as coupling partners under Rh(I)-catalysis. The reaction worked efficiently also with other analogous heterocyclic substrates and with a quinoline-N-oxide. We were able to obtain 6-(indol-3-yl)pyridinone and 8-(indol-3-yl)quinolone after cleavage of the directing group or rearrangement of the N-oxide moiety. 1,2-Amino alcohols are important structural motifs in organic chemistry that can be observed in natural products, pharmaceutically and biologically active molecules. The palladium-catalyzed difunctionalization of C-C multiple bonds has been broadly investigated as an efficient strategy to access such substructures. This transformation has been reported using either Pd(0)/Pd(II) or Pd(II)/Pd(IV) catalytic cycles, in which the nucleophilic functionalization of a putative Pd(II)-alkyl intermediate is achieved prior to beta-hydride elimination. As a further topic of this thesis, we developed new methods for the synthesis of amino alcohols whereby the Pd-catalyzed difunctionalization of alkynes and alkenes was combined with the tethering approach previously established in our laboratories. We first investigated the Pd-catalyzed enantioselective hydroalkoxylation of propargylic amines. The latter were tethered in situ with a trifluoroacetaldehyde hemiacetal. Best results were obtained with commercially available DACH-Phenyl Trost ligand. Aryl iodides were required as an additive in catalytic amount for successful outcome. A large variety of chiral oxazolidines were obtained in good to excellent yields and ee, followed by a diastereoselective reduction to give protected enantioenriched amino alcohols. A possible mechanism for this transformation relies on a Pd(0)/Pd(II) catalytic cycle involving oxidative addition of aryl iodide with a subsequent oxypalladation/protodemetallation (or reductive elimination) reaction. This is necessary to generate the active complex, not as the start of a cross-coupling event. The use of a commercially available DACH-Ph Trost ligand to produce high enantioselectivity in an unprecedented DYKAT process was critical to success.The Pd-catalyzed amino acetoxylation of cinnamyl alcohols was next taken into consideration towards the synthesis of valuable amino diol derivatives. In this case, preformed substrates were used, where the alcohol moiety was tethered to N-nucleophilic groups. Conditions involving Pd(II)/Pd(IV) catalysis and employing PIDA as a strong oxidant were employed. The use of this hypervalent iodine reagent was key to the success of the transformation. Amino acetoxylated products were obtained in moderate to good yields and dr. The scope of this reaction remains mostly limited to cinnamyl derived substrates. The reaction conditions did not tolerate substituents on the alpha, beta, and gamma positions of the allylic chains. Alkyl chain containing unsaturated alcohols delivered Aza-Wacker-type products.

EPFL2022

Ring-Opening Reactions of Aminocyclopropanes and Aminocyclobutanes

Mingming Wang

EPFL2022

Rh-catalyzed C-H Bond Heteroarylation with Hypervalent Iodine Reagents and Pd-Catalyzed Tethered Functionalizations of Carbon-Carbon Multiple Bonds.

Ashis Kumar Das

EPFL2022