Formation of Transient Anionic Metal Clusters in Palladium/Diene‐Catalyzed Cross‐Coupling Reactions

Abstract

Despite their considerable practical value, palladium/1,3‐diene‐catalyzed cross‐coupling reactions between Grignard reagents RMgCl and alkyl halides AlkylX remain mechanistically poorly understood. Herein, we probe the intermediates formed in these reactions by a combination of electrospray‐ionization mass spectrometry, UV/Vis spectroscopy, and NMR spectroscopy. According to our results and in line with previous hypotheses, the first step of the catalytic cycle brings about transmetalation to afford organopalladate anions. These organopalladate anions apparently undergo SN2‐type reactions with the AlkylX coupling partner. The resulting neutral complexes then release the cross‐coupling products by reductive elimination. In gas‐phase fragmentation experiments, the occurrence of reductive eliminations was observed for anionic analogues of the neutral complexes. Although the actual catalytic cycle is supposed to involve chiefly mononuclear palladium species, anionic palladium nanoclusters [PdnR(DE)n]−, (n=2, 4, 6; DE=diene) were also observed. At short reaction times, the dinuclear complexes usually predominated, whereas at longer times the tetra‐ and hexanuclear clusters became relatively more abundant. In parallel, the formation of palladium black pointed to continued aggregation processes. Thus, the present study directly shows dynamic behavior of the palladium/diene catalyst system and degradation of the active catalyst with increasing reaction time.

Second Comes First: Switching Elementary Steps in Palladium‐Catalyzed Cross‐Coupling Reactions

“…The fact that the organozinc reagent BuZnCl⋅LiCl failed to afford the corresponding organopalladate(0) complex suggests that only highly reactive organometallics, such as RMgCl and RLi, are capable of transferring their organyl group to the palladium(0) center of L 3 Pd. This behavior resembles the transmetalation of palladium diene complexes, but contrasts that of typical palladium(II) complexes, whose reactivity toward organozinc compounds and even milder transmetalation reagents is well known and forms the basis of synthetically most useful transformations, for example, Negishi and Suzuki–Miyaura cross‐coupling reactions …”

Handling considerations for the mass spectrometry of reactive organometallic compounds

“…The PSI flask is designed to have an inlet where inert gas (Ar or N 2 ) is introduced, and this positive pressure allows the solution in the flask to be introduced to the mass spectrometer via PEEK/PTFE tubing. 65 Reactions can be conducted at temperatures up to the boiling point of the solvent, and the PSI flask is designed in a way that contamination from the rubber septum leaching from the solvent can be avoided entirely, as seen in Figure 11. 66 PSI is straightforward to implement in any laboratory and allows continuous reaction monitoring.…”

Pressurized Sample Infusion

“…A look into palladium/diene‐catalyzed coupling of alkyl halides and Grignard reagents revealed that anionic Pd complexes are formed, and the mononuclear species are short‐lived – mainly favouring formation of small Pd nanoclusters [80] . The real‐time MS analysis afforded direct aggregation state information as well.…”

“…A look into palladium/diene-catalyzed coupling of alkyl halides and Grignard reagents revealed that anionic Pd complexes are formed, and the mononuclear species are shortlived -mainly favouring formation of small Pd nanoclusters. [80] The real-time MS analysis afforded direct aggregation state information as well. Additionally, the study discovered that the transmetalation step in these reactions actually precedes the oxidative addition step in the catalytic cycle.…”