Identification and Characterization of Intermediates in Transmetalation Reactions from Boron to Lithium and Copper
by Finn Kraft
Date of Examination:2024-04-17
Date of issue:2025-02-14
Advisor:Prof. Dr. Konrad Koszinowski
Referee:Prof. Dr. Konrad Koszinowski
Referee:Prof. Dr. Dietmar Stalke
Referee:Prof. Dr. Daniel Obenchain
Referee:PD Dr. Michael John
Referee:Dr. Holm Frauendorf
Persistent Address:
http://dx.doi.org/10.53846/goediss-11033
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Abstract
English
Transmetalation is a crucial elementary step in cross-coupling reactions. In this context, boron nucleophiles are especially popular and versatile, however, the fundamental details of transmetalation reactions involving these species have yet to be comprehensively understood. This thesis aims at investigating B/Cu and B/Li pre-transmetalation complexes to elucidate the factors that govern their reactivity using various mass-spectrometric methods and nuclear magnetic resonance spectroscopy, as well as modern tools of computational chemistry. The boron-based transmetalating agent applied was either (BPh4)–, (B(ArX)4 )– , where X is a para substituent, or ((R)(Ph)Bpin)– (R is either tBu or nBu and pin = pinacol). Solutions of these reagents with Cu(I) salts or alkali metal halides were prepared in MeCN or THF. nuclear magnetic resonance spectroscopic experiments revealed that in solution, Cu+/(BPh4)– complexes and Li+/((R)(Ph)Bpin)– complexes are unreactive at room temperature. At elevated temperatures and after prolonged reaction times, benzene formation was observed for both systems. While the copper complexes putatively undergo transmetalation and subsequent protonation of the phenylcopper species, the borinate ester supposedly reacts via direct protodeboronation. Although B-to-Cu transmetalations are frequently applied in synthetic chemistry, their detailed reaction mechanism is often unclear, yet adducts between the transmetalating agent and the metal center or complex are putative intermediates. For the systems described above, several of these adducts were identified in ESI-MS experiments, viz. [(MeCN)nCu2(B(ArX)4 )]+ (n = 0 or 2), the homodimers [Cu(B(ArX)4)2]– as well as the heterodimers [(B(ArX)4 )Cu(BPh4)]– (X = OMe, Me, F or Cl). Moreover, the post-transmetalation complexes [PhCu(BPh4)]–, [ArXCu(B(ArX)4 )]–, [ArXCu(BPh4)]– and [PhCu(B(ArX)4)]– were observed as well. Additionally, species of the type [(MX)((R)(Ph)Bpin)]– (X = Cl, Br, I or BF4; M = Li; Na or Cu and R = tBu or nBu) were observed. As the transmetalation reaction of the aforementioned molecular systems corresponds to an isomerization, their mass spectrometric analysis itself cannot distinguish between the presence of a pre- or post-transmetalation adduct in the experiment. Traveling wave ion mobility spectrometry mass spectrometry mass spectrometry and infrared photodissociation spectroscopy in combination with the calculated collision cross sections and calculated infrared spectra, respectively, showed that all (BPh4)– complexes are pre-transmetalation adducts. Collision-induced dissociation experiments on the these adducts showed that all ions preferably undergo transmetalations instead of dissociation of the transmetalating agent, which is fully in line with calculated reaction energies. A thermochemical analysis and an energy decomposition analysis showed that the B-to-Cu and B-to-Li phenyl transmetalation seems to be facilitated by (i) an overall positive complex charge, (ii) a low coordination state of the metal(I) ion and, (iii) by multielectron effects–but not by the electronegativity. These results point out that other reactivity descriptors need to be developed to correctly predict the favorability of such transmetalations. Branching ratios log α of the competing aryl/phenyl transmetalation reaction of [(BArX 4 )Cu(BPh4)]– were obtained from collision-induced dissociation experiments. These correlate well with Hammett-parameters σ-para X and the analysis revealed that electron-donating groups facilitate transmetalation. The good correlation between log α with the calculated ∆∆Gα298 values highlights the potential of theory to predict the reactivity of such systems.
Keywords: copper; boron; lithium; transmetalation; benchmarking; transition metal; physical organic chemistry; mass spectrometry; NMR; quantum chemistry; ion mobility mass spectrometry
