Revisiting the Mechanism and Origin of Selectivity in Pd(II) Catalyzed Conjugate Additions of Arylboronic Acids
Year: 2026
Type: preprint
Abstract: Pd(II) catalyzed conjugate additions of arylboronic acids to α,β-unsaturated carbonyls using PyDHIQ or PyOx ligands are widely used for the enantioselective synthesis of quaternary centers. Building on previous computational studies of this reaction, the transmetalation step was revisited to locate several previously unknown but energetically competitive transition structures, specifically an alternative favorable pathway for the transmetalation through a 4-membered transition state with the PyOx ligand. Extensive conformational sampling of the transition structures provides into the effect of the conformation of the PyDHIQ ligand on the selectivity in the synthesis of β-aryl, β-quaternary δ-lactams. The ligand adopts the ‘closed’ conformation in the selectivity-determining transition state. Detailed analysis of noncovalent and electrostatic interactions in the different conformations provides physical insights into the origin of the experimentally observed stereoselectivity.
Source: ChemRxiv
Institutions: University of Notre Dame, University of Georgia
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W7162499215