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Systematic Parameter Determination Aimed at a Catalyst-Controlled Asymmetric Rh(I)-Catalyzed Pauson–Khand Reaction

Year: 2024

Type: article

Abstract: ABSTRACT: Transition metal-catalyzed carbocyclization reactions have revolutionized the synthesis of complex cyclic organic compounds. Yet, subtle substrate changes can significantly alter reaction pathways. The asymmetric Rh(I)-catalyzed Pauson-Khand reaction (PKR) exemplifies such a reaction, being hindered by a narrow substrate scope and competing reactivity modes. In this study, we identified parameters predictive of yield and enantioselectivity in the catalyst-controlled asymmetric PKR, using 1,6-enynes with a 2,2-disubstituted alkene. In this way, ring-fused cyclopentenones can be formed with chiral quaternary carbon centers. Using bisphosphine ligand parameters from palladium complexes, including HOMO energy and the angle formed by the phosphorous aryl groups on the ligand, we established strong correlations with experimental % ee (R2=0.94 and 0.98) for two distinct precursors. Solvent dipole moments correlated with % ee for high dipole moment precursors (R2=0.97), while Abraham’s hydrogen bond basicity is more relevant for low dipole moment precursors (R2=0.93). Additionally, counterions were found to have a significant impact on PKR reactivity and selectivity, as does the steric demand of the alkyne substituent of the enyne precursor. In the latter case, %ee correlates with Sterimol B1 values for products with different alkyne substituents (R2=0.96). Furthermore, the computed C≡C wavenumber of the enyne precursor can be directly aligned with the yield of the asymmetric PKR.

Source: ACS Catalysis

DOI: 10.1021/acscatal.4c04490

Authors: Yifan Qi, Luke T. Jesikiewicz, Grace E. Scofield, Peng Liu, Kay M. Brummond

Institution: University of Pittsburgh

Language: English

Topic: Asymmetric Synthesis and Catalysis

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: hybrid

Estimated APC paid: $4,500