Premium
Metal‐Free Activation of C(sp 3 )–H Bond, and a Practical and Rapid Synthesis of Privileged 1‐Substituted 1,2,3,4‐Tetrahydroisoquinolines
Author(s) -
Choudhury Santosh Kumar,
Rout Pragati,
Parida Bibhuti Bhusan,
Florent JeanClaude,
Johannes Ludger,
Phaomei Ganngam,
Bertounesque Emmanuel,
Rout Laxmidhar
Publication year - 2017
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201700471
Subject(s) - chemistry , combinatorial chemistry , aryl , metal , isoquinoline , halide , base (topology) , stereochemistry , organic chemistry , mathematical analysis , alkyl , mathematics
The reaction of cotarnine and acyl/aryl ketones in “green” solvents provides an efficient approach to an array of privileged 1,2,3,4‐tetrahydroisoquinolines in excellent yields by metal‐free activation of C(sp 3 )–H bonds. This one‐pot procedure takes place under base‐free conditions at room temperature, and tolerates a wide range of functionalities. The reaction is highly chemoselective, can be performed on a multi‐gram scale, and pure products are isolated by simple filtration without workup. Interestingly, the complementary two‐step procedure from cotarnine halide salts gives the Mannich products in good yields. The scope was elaborated to 9‐bromocotarnine salts to access a range of 9‐bromonoscapine‐derived analogues. The methodology has been developed considering the structural similarity of cotarnine derivatives to noscapinoids, which represent an emerging class of microtubule‐modulating anticancer agents.