Cross-dehydrogenative N-N couplings.

The relatively high electronegativity of nitrogen makes N-N bond forming cross-coupling reactions particularly difficult, especially in an intermolecular fashion. The challenge increases even further when considering the case of dehydrogenative N-N coupling reactions, which are advantageous in terms of step and atom economy, but introduce the problem of the oxidant in order to become thermodynamically feasible. Indeed, the oxidizing system must be designed to activate the target N-H bonds, while at the same time avoid undesired N-N homocoupling as well as C-N and C-C coupled side products. Thus, preciously few intermolecular hetero N-N cross-dehydrogenative couplings exist, in spite of the central importance of N-N bonds in organic chemistry. This review aims at analyzing these few rare cases and provides a perspective for future developments.

Synthesis and [*C]CO-labelling of (C,N) gem-dimethylbenzylamine-palladium complexes for potential applications in positron emission tomography.

Various aryl-palladium complexes were synthesised from gem-dimethylbenzylamine derivatives by C-H activation under extremely mild conditions. Interestingly, these highly stable structures reacted with [13C]carbon monoxide to produce the desired labelled lactams in 29% to 51% yields over the C-H activation/carbonylation steps. As representative examples, a non-natural amino acid and an estradiol-based conjugate were prepared and labelled in model experiments with [13C]CO in homogeneous or heterogeneous conditions. Especially, the latter was radiolabelled with [11C]CO using a convenient procedure from the resin-supported palladium complex precursor. Thus, these results strongly suggest that cyclometallated palladium complexes obtained from gem-dimethylbenzylamine moieties are promising precursors for the practical synthesis of new [11C]tracers for Positron Emission Tomography.

Oxidative additions of alkynyl/vinyl iodides to gold and gold-catalyzed vinylation reactions triggered by the MeDalphos ligand.

The hemilabile Ad2P(o-C6H4)NMe2 ligand promotes fast, quantitative and irreversible oxidative addition of alkynyl and vinyl iodides to gold. The reaction is general. It works with a broad range of substrates of various electronic bias and steric demand, and proceeds with complete retention of stereochemistry from Z and E vinyl iodides. Both alkynyl and vinyl iodides react faster than aryl iodides. The elementary step is amenable to catalysis. Oxidative addition of vinyl iodides to gold and π-activation of alkenols (and N-alkenyl amines) at gold have been combined to achieve hetero-vinylation reactions. A number of functionalized heterocycles, i.e. tetrahydrofuranes, tetrahydropyranes, oxepanes and pyrrolidines were obtained thereby (24 examples, 87% average yield). Taking advantage of the chemoselectivity for vinyl iodides over aryl iodides, sequential transformations involving first a hetero-vinylation step and then a C-N coupling, a C-C coupling or an heteroarylation were achieved from a vinyl/aryl bis-iodide substrate.

Bioconjugated arylpalladium complexes on solid supports for a convenient last-step synthesis of 11C-labelled tracers for positron emission tomography.

Arylpalladium complexes prepared from o-iodobenzylalcohol-biomolecule conjugates and triphenylphosphine linked on polystyrene beads provided convenient supported and stable precursors. These heterogeneous substrates could react smoothly with [11C]CO, affording the corresponding 11C-labelled bioconjugates with isolated radiochemical yields ranging from 4% to 71%, and excellent radiochemical purities from 86% to >98% after a simple filtration. Thus, this method opens up a new pathway for an easier automation of Pd-catalysed syntheses of PET tracers.

Mechanistic and asymmetric investigations of the Au-catalysed cross-coupling between aryldiazonium salts and arylboronic acids using (P,N) gold complexes.

In order to explore the different mechanisms possibly occurring in the Au-catalysed cross-coupling of ArN2BF4 and ArB(OH)2 in the presence of CsF, various stoichiometric experiments were performed on gold complexes with (P,N) ligands. Employing 2-pyridylphenyl-diphenylphosphine allowed us to suggest three different mechanistic pathways, starting either with a transmetallation step, via two consecutive single electron transfers, or by implying a transmetallation between Au(i) and Au(iii) species. Moreover, when using commercially available chiral (P,N) ligands, the asymmetric formation of atropoisomeric biaryls from suitable aryldiazonium salts and arylboronic acids could be achieved with e.e. up to 26%.