Palladium-Catalyzed\nAsymmetric Larock Isoquinoline\nSynthesis to Access Axially Chiral 3,4-Disubstituted Isoquinolines

Larock isoquinoline synthesis is one of the most efficient\nand\nstraightforward approaches to the construction of 3,4-disubstituted\nisoquinolines. However, there have been no asymmetric versions for\nthe synthesis of axially chiral isoquinolines since their initial\nreport in 2001. Herein, we documented the first example of an asymmetric\nLarock isoquinoline synthesis by employing Pd(OAc)<sub>2</sub>/Walphos\nSL-W002–1 as the catalyst, affording the axially chiral 3,4-disubstituted\nisoquinolines with up to 97.5:2.5 er and 98% yield. Density Functional\nTheory (DFT) calculations clearly clarified the catalytic mechanism\nand the origin of the experimentally observed enantioselectivity.