Interplay between the Directing Group and Multifunctional Acetate Ligand in Pd-Catalyzed anti-Acetoxylation of Unsymmetrical Dialkyl-Substituted Alkynes

Abstract

The cooperative action of the acetate ligand, the 2-pyridyl sulfonyl (SO 2 Py) directing group on the alkyne substrate, and the palladium catalyst has been shown to be crucial for controlling reactivity, regioselectivity, and stereoselectivity in the acetoxylation of unsymmetrical internal alkynes under mild reaction conditions. The corresponding alkenyl acetates were obtained in good yields with complete levels of β-regioselectivity and anti -acetoxypalladation stereocontrol. Experimental and computational analyses provide insight into the reasons behind this delicate interplay between the ligand, directing group, and the metal in the reaction mechanism. In fact, these studies unveil the multiple important roles of the acetate ligand in the coordination sphere at the Pd center: (i) it brings the acetic acid reagent into close proximity to the metal to allow the simultaneous activation of the alkyne and the acetic acid, (ii) it serves as an inner-sphere base while enhancing the nucleophilicity of the acid, and (iii) it acts as an intramolecular acid to facilitate protodemetalation and regeneration of the catalyst. Further insight into the origin of the observed regiocontrol is provided by the mapping of potential energy profiles and distortion–interaction analysis.

The Mechanism of Rh(I)-Catalyzed Coupling of Benzotriazoles and Allenes Revisited: Substrate Inhibition, Proton Shuttling, and the Role of Cationic vs Neutral Species

“…A second transition state (Δ G INT7→TS7–8 = 36.0 kJ·mol –1 ) was found as well as INT8 , a σ-allyl complex. In general, this type of ligand-assisted proton shuttling (LAPS) as a special case of metal–ligand cooperation has been proposed before for various catalytic and stoichiometric transformations. − Examples for Rh­(I) catalysis are however scarce …”

Palladium(ii)-catalyzed 1,3-heteroaryl acyloxylation of propargylic electrophiles

“…8 Only a few successful methods have been disclosed, which usually required the installment of directing groups (Scheme 1A). 9 For instance, Li et al reported the use of a 2-pyridyloxy moiety under ruthenium catalysis. 9 b In 2022, Corpas and Arrayás et al found that the SO 2 Py directing group facilitated the palladium-catalyzed anti -acetoxylation reaction of unsymmetrical dialkyl alkynes.…”

Gold-catalyzed four-component multifunctionalization of alkynes

“…1a). In general, the regioselectivity in alkyne functionalization can be well understood in most cases of terminal and conjugated alkynes but it constitutes the most challenging issue for otherwise unbiased internal alkynes 15 , in which the directing group has been used increasingly in attempts to improve the regioselectivity of the reaction [16][17][18][19][20][21][22] .…”