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

Abstract

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 switching propargylic C–H functionalization. The energetically most preferred pathway is found to proceed through (a) BF₃-assisted abstraction of methoxide, (b) proton transfer from tetramethylpiperidine (TMPH) to dienes, and (c) C–C bond formation between propargyl and allyl moieties to furnish the 1,5-enyne products. The MeOBF₃⁻ generated in situ 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 nucleophilic addition. Both stereoisomers of the product could be accessed by changing the chirality of ligands. The chiral induction was found to depend on the synergy that exists among the chiral portion of the phosphoramidites and the counterion MeOBF₃⁻. Due to the ligand chirality changes in the catalytic microenvironment, the noncovalent interactions (NCIs) are differentiated between the chiral cavity and the counterion in the diastereoselective transition states, and an efficient and selective conversion is achieved. This study not only provides a deep mechanistic understanding of the diastereoselective propargylic C–H functionalization but also discloses a counterion–ligand cooperative strategy for precise stereocontrol in asymmetric catalysis.