DDQ-Promoted Mild and Efficient Metal-Free Oxidative α-Cyanation of <i>N</i>-Acyl/Sulfonyl 1,2,3,4-Tetrahydroisoquinolines
Hong Pyo Kim,
Heesun Yu,
Hyoungsu Kim,
Seok-Ho Kim,
Dongjoo Lee
Affiliations
Hong Pyo Kim
College of Pharmacy and Research Institute of Pharmaceutical Science and Technology (RIPST), Ajou University, 206 Worldcup-ro, Yeongtong-gu, Suwon 16499, Korea
Heesun Yu
College of Pharmacy and Research Institute of Pharmaceutical Science and Technology (RIPST), Ajou University, 206 Worldcup-ro, Yeongtong-gu, Suwon 16499, Korea
Hyoungsu Kim
College of Pharmacy and Research Institute of Pharmaceutical Science and Technology (RIPST), Ajou University, 206 Worldcup-ro, Yeongtong-gu, Suwon 16499, Korea
Seok-Ho Kim
Department of Pharmacy, College of Pharmacy and Institute of Pharmaceutical Sciences, CHA University, 120 Haeryong-ro, Gyeonggi-do, Pocheon 11160, Korea
Dongjoo Lee
College of Pharmacy and Research Institute of Pharmaceutical Science and Technology (RIPST), Ajou University, 206 Worldcup-ro, Yeongtong-gu, Suwon 16499, Korea
A mild and highly efficient metal-free oxidative α-cyanation of N-acyl/sulfonyl 1,2,3,4-tetrahydroisoquinolines (THIQs) has been accomplished at an ambient temperature via DDQ oxidation and subsequent trapping of N-acyl/sulfonyl iminium ions with (n-Bu)3SnCN. Employing readily removable N-acyl/sulfonyl groups as protecting groups rather than N-aryl ones enables a wide range of applications in natural product synthesis. The synthetic utility of the method was illustrated using a short and efficient formal total synthesis of (±)-calycotomine in three steps.
