Sterically hindered substrates can be employed in an enantioselective palladium-catalyzed α-arylation with the chiral monophosphorus ligand BI-DIME. This process enabled an efficient synthesis of the antidepressant (S)-nafenodone, a four-step enantioselective synthesis of the Sceletium alkaloid (+)-sceletium A-4, a concise five-step enantioselective synthesis of (-)-corynoline, as well as a three-step preparation of (-)-DeN-corynoline.

We herein report the development of a sterically hindered and electron-rich P-chiral monophosphorus biaryl ligand that has enabled a general and efficient enantioselective intramolecular α-arylation, providing access to a wide series of [4.4], [4.5], and [4.6]-spirocycles with chiral benzylic quaternary carbons in high yields with good to excellent enantioselectivities. A pronounced water effect on enantioselectivity is observed.

Sterically hindered substrates can be employed in an enantioselective palladium-catalyzed a-arylation with the chiral monophosphorus ligand BI-DIME. This process enabled an efficient synthesis of the antidepressant (S)-nafenodone,af our-step enantioselective synthesis of the Sceletium alkaloid (+ +)-sceletium A-4, aconcise five-step enantioselective synthesis of (À)-corynoline,aswell as athree-step preparation of (À)-DeN-corynoline.