Mechanism of Stereoinduction in Asymmetric Synthesis of Highly Functionalized 1,2-Dihydroquinolines and 2H-1-Benzopyrans via Nonracemic Palladacycles with a Metal-Bonded Stereogenic Carbon

To establish the synthetic utility of palladacycles, a stable racemic benzannulated azapalladacycle featuring a palladium-bonded sp3-hybridized stereogenic carbon was prepared and converted into a series of racemic 2,3,4-trisubstituted 1,2-dihydroquinolines via a regioselective insertion of activated alkynes (RC⋮CCOOEt). Analogous diastereomerically enriched azapalladacyle (92% de) and oxapalladacycle (64% de) were synthesized from arylpalladium(II) iodo complexes possessing a nonracemic spectator ligand ((1R,2R)-N,N,N ‘,N ‘-tetramethyl-1,2-diaminocyclohexane) via an intramolecular displacement of the iodide by an ester enolate. Absolute configurations of the metal-bonded stereocenters in the diastereomerically enriched palladacycles were unequivocally assigned, and the efficiency of stereoinduction was systematically studied. On the basis of these experiments, a plausible mechanism for the transfer of chirality from the nonracemic auxiliary ligand to the palladium-bonded stereogenic carbon was proposed. A restricted rotation about the palladium-aryl bond in arylpalladium(II) iodo complexes giving rise to atropisomers, as well as the nature of the leaving group (iodide or acetate), were found to play a crucial role in the chirality transfer process. Diastereomerically enriched palladacycles underwent a ligand exchange with triphenylphosphine followed by regioselective insertion of unsymmetrical alkynes to afford nonracemic 1,2-dihydroquinolines (six examples) in excellent 80−91% ee and 2H-1-benzopyrans (four examples) in 32−56% ee.