Base-Free Cross-Couplings of Aryl Diazonium Salts in Methanol: PdII -Alkoxy as Reactivity-Controlling Intermediate.

Pd-catalyzed cross-coupling reactions of aryl diazonium salts are generally assumed to proceed via cationic PdII intermediates which in turn would be highly reactive in the subsequent transmetalation step. Contrary to this belief, we herein report our observation and rationalization of opposing reactivities of ArN2+ in Suzuki (=effective) and Stille (=ineffective) cross-couplings in MeOH. Our systematic experimental and computational studies on the roles of transmetalating agent, solvent, base and the likely involvement of in situ formed diazoether derivatives challenge the currently accepted mechanism. Our data suggest that the observed solvent dichotomy is primarily due to PdII -methoxy intermediates being formed, which are unreactive with arylstannanes, but highly reactive with arylboronic acids, complementing the Suzuki "Pd-oxy" mechanism with the direct demonstration of transmetalation of a PdII -alkoxy complex. Lewis acids were found to circumvent this reactivity divergence, promoting efficient couplings regardless of the employed conditions or coupling partners.

Selenolation of Aryl Iodides and Bromides Enabled by a Bench-Stable PdI Dimer.

The use of an air- and moisture-stable dinuclear PdI complex as an efficient catalyst for the formation of C(sp2 )-SeR bonds is here reported. The privileged reactivity of the PdI dimer allows for the direct use of selenolates as nucleophiles in the cross-coupling. Although previous methodologies suffer from catalyst poisoning through the formation of Pd-ate complexes, the mechanistically distinct dinuclear PdI catalyst circumvents this challenge. A wide variety of aryl bromides and iodides were efficiently coupled under relatively mild reaction conditions with broad functional group tolerance. Mechanistic and computational data are presented in support of direct PdI reactivity.

Orthogonal Nanoparticle Catalysis with Organogermanes.

Although nanoparticles are widely used as catalysts, little is known about their potential ability to trigger privileged transformations as compared to homogeneous molecular or bulk heterogeneous catalysts. We herein demonstrate (and rationalize) that nanoparticles display orthogonal reactivity to molecular catalysts in the cross-coupling of aryl halides with aryl germanes. While the aryl germanes are unreactive in Ln Pd0 /Ln PdII catalysis and allow selective functionalization of established coupling partners in their presence, they display superior reactivity under Pd nanoparticle conditions, outcompeting established coupling partners (such as ArBPin and ArBMIDA) and allowing air-tolerant, base-free, and orthogonal access to valuable and challenging biaryl motifs. As opposed to the notoriously unstable polyfluoroaryl- and 2-pyridylboronic acids, the corresponding germanes are highly stable and readily coupled. Our mechanistic and computational studies provide unambiguous support of nanoparticle catalysis and suggest that owing to the electron richness of aryl germanes, they preferentially react by electrophilic aromatic substitution, and in turn are preferentially activated by the more electrophilic nanoparticles.

Site-Selective C-S Bond Formation at C-Br over C-OTf and C-Cl Enabled by an Air-Stable, Easily Recoverable, and Recyclable Palladium(I) Catalyst.

This report widens the repertoire of emerging PdI catalysis to carbon-heteroatom, that is, C-S bond formation. While Pd0 -catalyzed protocols may suffer from the formation of poisonous sulfide-bound off-cycle intermediates and lack of selectivity, the mechanistically diverse PdI catalysis concept circumvents these challenges and allows for C-S bond formation (S-aryl and S-alkyl) of a wide range of aryl halides. Site-selective thiolations of C-Br sites in the presence of C-Cl and C-OTf were achieved in a general and a priori predictable fashion. Computational, spectroscopic, X-ray, and reactivity data support dinuclear PdI catalysis to be operative. Contrary to air-sensitive Pd0 , the active PdI species was easily recovered in the open atmosphere and subjected to multiple rounds of recycling.

Divergent Reactivity of Stannane and Silane in the Trifluoromethylation of PdII : Cyclic Transition State versus Difluorocarbene Release.

The transmetalation is a key elementary step in cross-coupling reactions. Yet, the precise nature of its mechanism and transition state geometry are frequently elusive. This report discloses our study of the transmetalation of [PdII ]-F complexes with the silane- and stannane-based trifluoromethylation agents, R3 SiCF3 and R3 SnCF3 . A divergent reactivity was uncovered, with the stannane showing selective R-group transfer, and the silane selective CF3 -group transfer. Using a combined experimental and computational approach, we uncovered a hitherto unrecognized transmetalation mechanism with the widely employed R3 SiCF3 reagent, explaining its unique activity in metal-catalyzed trifluoromethylations. While the stannane reacts via a cyclic, 4-membered transition state, the silane undergoes a fundamentally different pathway and releases a difluorocarbene in the transmetalation event. Molecular dynamics studies clearly reinforced the liberation of a free CF2 carbene, which reacts with [PdII ]-F to ultimately generate [PdII ]-CF3.

Post-Transition-State Dynamic Effects in the Transmetalation of Pd(II)-F to Pd(II)-CF3.

The observation of post-transition-state dynamic effects in the context of metal-based transformation is rare. To date, there has been no reported case of a dynamic effect for the widely employed class of palladium-mediated coupling reactions. We performed an experimental and computational study of the trifluoromethylation of Pd(II)F, which is a key step in the Pd(0)/Pd(II)-catalyzed trifluoromethylation of aryl halides or acid fluorides. Our experiments show that the cis/trans speciation of the formed Pd(II)CF3 is highly solvent- and transmetalation reagent-dependent. We employed GFN2-xTB- and B3LYP-D3-based molecular dynamics trajectory calculations (with and without explicit solvation) along with high-level QM calculations and found that depending on the medium, different transmetalation mechanisms appear to be operative. A statistically representative number of Born-Oppenheimer molecular dynamics (MD) simulations suggest that in benzene, a difluorocarbene is generated in the transmetalation with R3SiCF3, which subsequently recombines with the Pd via two distinct pathways, leading to either the cis- or trans-Pd(II)CF3. Conversely, GFN2-xTB simulations in MeCN suggest that in polar/coordinating solvents an ion-pair mechanism is dominant. A CF3 anion is initially liberated and then rebinds with the Pd(II) cation to give a cis- or trans-Pd(II). In both scenarios, a single transmetalation transition state gives rise to both cis- and trans-species directly, owing to bifurcation after the transition state. The potential subsequent cis- to trans isomerization of the Pd(II)CF3 was also studied and found to be strongly inhibited by free phosphine, which in turn was experimentally identified to be liberated through displacement by a polar/coordinating solvent from the cis-Pd(II)CF3 complex. The simulations also revealed how the variation of the Pd-coordination sphere results in divergent product selectivities.