Different Oxidative Addition Mechanisms for 12- and 14-Electron Palladium(0) Explain Ligand-Controlled Divergent Site Selectivity

Abstract

In cross-coupling reactions, dihaloheteroarenes are usually most reactive at C–halide bonds adjacent to a heteroatom. This selectivity has been previously rationalized. However, no mechanistic explanation exists for anomalous reports in which specific ligands effect inverted selectivity with dihalopyridines and -pyridazines. Here we provide evidence that these ligands uniquely promote oxidative addition at 12e– Pd(0). Computations indicate that 12e– and 14e– Pd(0) can favor different mechanisms for oxidative addition due to differences in their HOMO symmetries. These mechanisms are shown to lead to different site preferences, where 12e– Pd(0) can favor oxidative addition at an atypical site distal to nitrogen.

Catalyst-controlled regioselective Sonogashira coupling of 9-substituted-6-chloro-2,8-diiodopurines

“…Although there is only 6% higher coefficient at C8 than at C2, it is a significant value because the difference in the BDE which can affect selectivity is so low that it can be considered negligible. 24,25 Thus, for the mono-ligated PdL 1 species, the C8-selective product was formed as the major product. In the case of PdL 2 , we considered not only the π* LUMO substrate but also the σ* LUMO substrate because the HOMO of PdL 2 has π symmetry.…”

“…To gain some insight into this, we performed the Density Function Theory (DFT) calculation using Gaussian 09 18 and attempted to elucidate the rationale behind the observed selectivity based on the literature related to the current work. 19–27…”

“…1C). 24 Based on their concept, herein, considering the relative ease of the oxidative addition to C8-I vs . C2-I, and because the σ symmetry of the HOMO PdL1 can interact with the π* LUMO substrate dominantly, the difference in the coefficients at the ipso carbons (C2 or C8) in the π* LUMO substrate becomes the most important factor.…”

“…To gain some insight into this, we performed the Density Function Theory (DFT) calculation using Gaussian 09 18 and attempted to elucidate the rationale behind the observed selectivity based on the literature related to the current work. [19][20][21][22][23][24][25][26][27] Some studies have proposed that the mono-ligated PdL 1 and the bis-ligated PdL 2 as the activated forms resulted in a big difference in the formation of the transition state, which led to regioselectivity for the oxidative addition of the aryl halide containing identical halides. 19 However, according to Table 3, the small ligands most likely react via PdL 2 (entry 10), and the large ligands most likely react via the PdL 1 species (entries 12 and 13), and they show the same trend toward selectivity.…”

“…1C). 24 Based on their concept, herein, considering the relative ease of the oxidative addition to C8-I vs. C2-I, and because the σ symmetry of the HOMO PdL1 can interact with the π* LUMO substrate dominantly, the difference in the coefficients at the ipso carbons (C2 or C8) in the π* LUMO substrate becomes the most important factor. Although there is only 6% higher coefficient at C8 than at C2, it is a significant value because the difference in the BDE which can affect selectivity is so low that it can be considered negligible.…”