Direct and Efficient C(sp3)-H Functionalization of N-Acyl/Sulfonyl Tetrahydroisoquinolines (THIQs) With Electron-Rich Nucleophiles via 2,3-Dichloro-5,6-Dicyano-1,4-Benzoquinone (DDQ) Oxidation

Heesun Yu; Hyoungsu Kim; Seung-Hoon Baek; Dongjoo Lee

doi:10.3389/fchem.2020.00629

Direct and Efficient C(sp³)-H Functionalization of N-Acyl/Sulfonyl Tetrahydroisoquinolines (THIQs) With Electron-Rich Nucleophiles via 2,3-Dichloro-5,6-Dicyano-1,4-Benzoquinone (DDQ) Oxidation

Front Chem. 2020 Jul 29:8:629. doi: 10.3389/fchem.2020.00629. eCollection 2020.

Authors

Heesun Yu¹, Hyoungsu Kim¹, Seung-Hoon Baek¹, Dongjoo Lee¹

Affiliation

¹ Research Institute of Pharmaceutical Science and Technology (RIPST), College of Pharmacy, Ajou University, Suwon, South Korea.

Abstract

A highly efficient metal-free oxidative direct C(sp³)-H functionalization of N-acyl/sulfonyl 1,2,3,4-tetrahydroisoquinolines (THIQs) with a wide range of electron-rich nucleophiles was accomplished under mild conditions through oxidation with DDQ and subsequent trapping of the resulting reactive and stable N-acyl/sulfonyl iminium ions. The synthetic utility of this method was illustrated by a concise and efficient total synthesis of (±)-benzo[a]quinolizidine (10) in 3 steps from the known N-Cbz 1,2,3,4-THIQ 4b.

Keywords: DDQ; electron-rich; natural products; oxidation; tetrahydroisoquinoline.