Mechanistic Insights and Implications of Dearomative Rearrangement in Copper-Free Sonogashira Cross-Coupling Catalyzed by Pd-Cy*Phine

Abstract

The reaction mechanism for the in situ prepared Pd-Cy*Phine catalyst used in copper-free Sonogashira coupling was investigated using density functional theory. In addition, the significance of the meta-terarylphosphine ligand architecture of Cy*Phine was probed, as it had been previously shown experimentally to augment catalytic activity relative to its biarylphosphine analogue, XPhos. The calculated reaction barriers and free energies for the steps in the catalytic cycle suggest that the suppression of a dearomative rearrangement pathway is likely to be an important feature for the improved catalytic performance observed for the Pd-Cy*Phine system.

Empirical and Computational Insights into N‐Arylation Reactions Catalyzed by Palladium meta‐Terarylphosphine Catalyst

“…Intermediate LM2 may also undergo off‐cycle DR pathways, in which the ligand L may be modified. In our previous study on copper‐free Sonogashira cross‐coupling, the meta ‐terarylphosphine architecture was shown to hinder a deleterious off‐cycle DR of the catalyst . Herein, the barriers for DR were calculated to be notably higher than that for the AB step, at 102.1 and 164.7 kJ mol −1 for Pd–XPhos and Pd–Cy*Phine, respectively.…”

“…However, an alternative fate is plausible for LM2 with a potentially lower barrier for both Pd–XPhos and Pd–Cy*Phine. Drawing on our insights from the previous study on the mechanism of copper‐free Sonogashira cross‐coupling reactions, a likely possibility is a BAB pathway for LM2 to LM3A (Figure , blue). In this case, BAB for Cy*Phine has a much lower barrier of 25.7 kJ mol −1 , corresponding to the coordination of t BuO − to S2 , which provides a viable off‐cycle route of LM2 towards the end products.…”

Magnesium oxide supported bimetallic Pd/Cu nanoparticles as an efficient catalyst for Sonogashira reaction

“…Also, reactions of aryl iodides with other alkynes such as propargyl alcohol and 4-ethynyltoluene, and 1-octyneproceed efficiently affording the corresponding alkynes in high to excellent yields (Table 2, entries 10-14). Furthermore, reactions of different aryl bromides as well as heterocyclic 5-bromopyrimidine and 2-bromopyridine proceed efficiently at 60-80 ºC by increasing the loading to 0.2 mol% Pd affording the desired products in high to excellent yields ( Table 2, entries [15][16][17][18][19][20][21][22][23]. It should be noted that reactions of 4nitrobromobenzene and 4-bromobenzaldehyde in the absence of Cu using Pd@MgO ( Table 2, entries [24][25] and also in the absence of Pd using Cu@MgO ( Table 2, entry 26) gave very low yields for desired products.…”

Mechanism of copper-free Sonogashira reaction operates through palladium-palladium transmetallation

“…Instead, the formation of B was proposed to take place through a reversible π-coordination of the alkyne reagent to complex A into η 2 -alkyne–palladium intermediate C and subsequent base mediated deprotonation of the terminal acetylenic proton. Although great deal of experimental and theoretical effort has been undertaken in support of this mechanism 22 – 31 , numerous questions are still open and the proposed model remains unconfirmed. Adversely, recent thorough computational investigations revealed a relatively high activation barrier for the formation of π-complex C from the acetylene and the oxidative adduct A , for example, refs.…”

“…Adversely, recent thorough computational investigations revealed a relatively high activation barrier for the formation of π-complex C from the acetylene and the oxidative adduct A , for example, refs. 26 , 27 , 31 .…”