Mechanistic insights into ligand-controlled diastereoselectivity in iridium-catalyzed stereoselective coupling of allylic ethers and alkynes: a DFT perspective

Regulating the diastereoselectivity of a reaction is highly attractive but extremely challenging, density functional theory computations are employed to investigate an iridium-catalyzed ligand-controlled diastereoselectivity switch propargylic C−H functionalization. Energetically most preferred pathway is found to proceed through (a) BF3-assisted abstraction of methoxide, (b) proton transferred from the tetramethylpiperidine (TMPH) to the unsaturated bond of dienes, and (c) C−C bond formation between propargyl and allyl moiety to furnish the synthetically versatile 1,5-enyne products. The MeOBF3− generated in situ generation is found to remain associated between the ligand and incoming substrates as a counterion, and plays a key role in controlling the diastereoselectivity in the enantiocontrolled (as well as the turn-over determining step) nucleophilic addition. All two stereoisomers of the product bearing two contiguous stereogenic centers could be accessed by changing the chirality of ligands, the chiral induction was found to depend on the synergy that exists among chiral portion of the phosphoramidites and the counterion MeOBF3−. Due to the ligand chirality changes in the catalytic microenvironment, the noncovalent interactions (NCIs) is differentiated between the chiral cavity and the counterion in the diastereoselective transition states, therefore, the efficient and selective conversion is achieved. Therefore, a counterion-ligand cooperative induced stereocontrol approach is proposed, the corresponding NCIs in stereocontrolling transition states are found to be the differentiating factors rendering the stereochemically distinct transition states to be the lowest energy one. This study not only provides a deep mechanistic understanding of the diastereoselectivity propargylic C−H functionalization but also establishes a novel counterion-ligand cooperative strategy for precise stereocontrol, offering a versatile and efficient approach for the synthesis of complex chiral molecules in asymmetric catalysis.