Trifluoromethylation reactions have recently received increased attention because of the beneficial effect of the trifluoromethyl group on the pharmacological properties of numerous substances. A common method to introduce the trifluoromethyl group employs the Ruppert–Prakash reagent, that is, Si(CH₃)₃CF₃, together with a copper(I) halide. We have applied this method to the trifluoromethylation of aromatic alkynes and used electrospray-ionization mass spectrometry to investigate the mechanism of these reactions in tetrahydrofuran, dichloromethane, and acetonitrile as well as with and without added 1,10-phenanthroline. In the absence of the alkyne component, the homoleptic ate complexes [Cu(CF₃)₂]⁻ and [Cu(CF₃)₄]⁻ were observed. In the presence of the alkynes RH, the heteroleptic complexes [Cu(CF₃)₃R]⁻ were detected as well. Upon gas-phase fragmentation, these key intermediates released the cross-coupling products R−CF₃ with perfect selectivity. Apparently, the [Cu(CF₃)₃R]⁻ complexes did not originate from homoleptic cuprate anions, but from unobservable neutral precursors. The present results moreover point to the involvement of oxygen as the oxidizing agent.

Grignard reagents RMgCl and their so-called turbo variant, the highly reactive RMgCl⋅LiCl, are of exceptional synthetic utility. Nevertheless, it is still not fully understood which species these compounds form in solution and, in particular, in which way LiCl exerts its reactivity-enhancing effect. A combination of electrospray-ionization mass spectrometry, electrical conductivity measurements, NMR spectroscopy (including diffusion-ordered spectroscopy), and quantum chemical calculations is used to analyze solutions of RMgCl (R=Me, Et, Bu, Hex, Oct, Dec, iPr, tBu, Ph) in tetrahydrofuran and other ethereal solvents in the absence and presence of stoichiometric amounts of LiCl. In tetrahydrofuran, RMgCl forms mononuclear species, which are converted into trinuclear anions as a result of the concentration increase experienced during the electrospray process. These trinuclear anions are theoretically predicted to adopt open cubic geometries, which remarkably resemble structural motifs previously found in the solid state. The molecular constituents of RMgCl and RMgCl⋅LiCl are interrelated via Schlenk equilibria and fast intermolecular exchange processes. A small portion of the Grignard reagent also forms anionic ate complexes in solution. The abundance of these more electron-rich and hence supposedly more nucleophilic ate complexes strongly increases upon the addition of LiCl, thus rationalizing its beneficial effect on the reactivity of Grignard reagents.

Molybdenum pentachloride is an unusually powerful reagent for the dehydrogenative coupling of arenes. Owing to the high reaction rate using MoCl₅, several labile moieties are tolerated in this transformation. The mechanistic course of the reaction was controversially discussed although indications for a single electron transfer as the initial step were found recently. Herein, based on a combined study including synthetic investigations, electrochemical measurements, EPR spectroscopy, DFT calculations, and mass spectrometry, we deduct a highly consistent mechanistic scenario: MoCl₅ acts as a one-electron oxidant in the absence of TiCl₄ and as two-electron oxidant in the presence of TiCl₄, but leads to an over-oxidized intermediate in both cases, which protects it from side reactions. In the course of aqueous work-up the reagent waste (Mo^III/IV species) acts as reducing agent generating the desired organic C−C coupling product.

Molybdänpentachlorid ist ein effizientes Reagens für die dehydrierende Kupplung von Arenen. Wegen der hohen Reaktionsgeschwindigkeit bei der Umsetzung mit MoCl₅ wird eine Reihe von labilen Molekülbereichen in dieser Transformation toleriert. Der mechanistische Verlauf der Reaktion wurde bislang sehr kontrovers diskutiert, auch wenn vor kurzem Hinweise gefunden wurden, dass ein Ein-Elektronen-Transfer die Umsetzung einleitet. Hier kann aus einer kombinierten Studie in Form von systematischen Syntheseversuchen, elektrochemischen Messungen, EPR-Spektroskopie, DFT-Rechnungen und Massenspektrometrie eine hochkonsistente mechanistische Vorstellung abgeleitet werden. MoCl₅ fungiert als Ein-Elektronen-Oxidationsmittel in der Abwesenheit von TiCl₄ und als Zwei-Elektronen-Oxidationsmittel in Gegenwart von TiCl₄. In beiden Fällen führt es zu einem überoxidierten Intermediat, das die Zielstruktur vor Nebenreaktionen schützt. Im Zuge der wässrigen Aufarbeitung wirkt der Reagensabfall (Mo^III/IV-Verbindungen) als Reduktionsmittel und liefert das gewünschte organische C-C-Kupplungsprodukt.

Conjugate additions of organocuprates are of outstanding importance for organic synthesis. To improve our mechanistic understanding of these reactions, we have used electrospray ionization mass spectrometry for the identification of the ionic intermediates formed upon the treatment of LiCuR₂⋅LiCN (R=Me, Bu, Ph) with a series of α,β-unsaturated nitriles. Acrylonitrile, the weakest Michael acceptor included, did not afford any detectable intermediates. Fumaronitrile (FN) yielded adducts of the type Li_n−1Cu_nR_2n(FN)_n⁻, n=1–3. When subjected to fragmentation in the gas phase, these adducts were not converted into the conjugate addition products, but re-dissociated into the reactants. In contrast, the reaction with 1,1-dicyanoethylene furnished the products of the conjugate addition without any observable intermediates. Tri- and tetracyanoethylene proved to be quite reactive as well. The presence of several cyano groups in these substrates opened up reaction pathways different from simple conjugate additions, however, and led to dimerization and substitution reactions. Moreover, the gas-phase fragmentation behavior of the species formed from these substrates indicated the occurrence of single-electron transfer processes. Additional quantum-chemical calculations provided insight into the structures and stabilities of the observed intermediates and their consecutive reactions.

Pd-mediated Negishi cross-coupling reactions were studied by a combination of kinetic measurements, electrospray-ionization (ESI) mass spectrometry, ³¹P NMR and UV/Vis spectroscopy. The kinetic measurements point to a rate-determining oxidative addition. Surprisingly, this step seems to involve not only the Pd catalyst and the aryl halide substrate, but also the organozinc reagent. In this context, the ESI-mass spectrometric observation of heterobimetallic Pd–Zn complexes [L₂PdZnR]⁺ (L=S-PHOS, R=Bu, Ph, Bn) is particularly revealing. The inferred presence of these and related neutral complexes with a direct Pd–Zn interaction in solution explains how the organozinc reagent can modulate the reactivity of the Pd catalyst. Previous theoretical calculations by González-Pérez et al. (Organometallics­ 2012, 31, 2053) suggest that the complexation by the organozinc reagent lowers the activity of the Pd catalyst. Presumably, a similar effect also causes the rate decrease observed upon addition of ZnBr₂. In contrast, added LiBr apparently counteracts the formation of Pd–Zn complexes and restores the high activity of the Pd catalyst. At longer reaction times, deactivation processes due to degradation of the S-PHOS ligand and aggregation of the Pd catalyst come into play, thus further contributing to the appreciable complexity of the title reaction.

We have used a combination of electrospray ionization mass spectrometry and electrical conductivity measurements to analyze solutions of the Gilman cuprates LiCuR₂⋅LiX, with R=Ph, Bu and X=Cl, Br, I, in tetrahydrofuran and have compared our findings with previous results on cyanocuprates LiCuR₂⋅LiCN. Among the various polynuclear organocuprate ions observed, Li₂Cu₃Ph₆⁻, LiCu₄Ph₆⁻, and Cu₅Ph₆⁻ are of particular interest because aggregates of the same composition are known from X-ray crystal structures. Control experiments have indicated that the polynuclear organocuprate anions detected in solution are indeed identical to those formed in the solid state. As abundant ions of the type Li₂Cu₃R₆⁻ are found in solutions of Gilman cuprates and cyanocuprates alike, their possible involvement in organocuprate reactions should be considered. For comparison, we have also included solutions of LiCu(R)I, LiCuX₂⋅LiX, LiCuX₂, and CuCN⋅2 LiX in the present study.