title: Three-Step Catalytic Asymmetric Total Syntheses of 13-Methyltetrahydroprotoberberine Alkaloids.
abstract: (S,R)-N-PINAP was identified to be the chiral ligand for highly enantioselective CuI-catalyzed reaction of tetrahydroisoquinolines (THIQs), alkynes, and 2-bromobenzaldehyde derivatives. This enables us to accomplish the first asymmetric total synthesis of 12 natural 13-methyltetrahydroprotoberberine (13-MeTHPB) alkaloids in only three catalytic steps with 47-64% overall yields. In addition, the Pd-catalyzed reductive Heck cyclization was successfully extended to three Pd-catalyzed domino reactions (Heck/Suzuki, Heck/Sonogashira, and Heck/Heck), which greatly expands the synthetic utility of this catalytic strategy and allows expeditious access to 13-substituted tetrahydroprotoberberines for further bioactivity evaluation.
authors.affiliation: Department of Chemistry, The Hong Kong University of Science and Technology , Clearwater Bay, Kowloon, Hong Kong, China.
authors.forename: Shiqiang
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Department of Chemistry, The Hong Kong University of Science and Technology , Clearwater Bay, Kowloon, Hong Kong, China.
authors.forename: Rongbiao
authors.identifier: 0000-0002-2740-5222
authors.initials: R
authors.lastname: Tong