Scalable direct N-methylation of drug-like amines using 12CO2/13CO2 by simple inorganic base catalysis  

作　　者：Chunlei Lua Zetian Qiu Yiling Zhu Bo-Lin Lin 

机构地区：[1]School of Physical Science and Technology (SPST),ShanghaiTech University,Shanghai 201210,China [2]Shanghai Institute of Organic Chemistry,Chinese Academy of Sciences,Shanghai 200032,China [3]University of Chinese Academy of Sciences,Beijing 100049,China

出　　处：《Science Bulletin》2019年第11期723-729,共7页科学通报（英文版）

基　　金：supported by the National Natural Science Foundation of China(U1532135)

摘　　要：With the growing urgency of potential catastrophic climate changes due to anthropogenic CO2 emissions,numerous efforts have been devoted to development of synthetic protocols using CO2 as a building block in organic reactions, but the general applicability to complex drug-like substrates remains a challenge.We develop a general protocol for scalable direct N-methylation of a wide-scope drug-like amines using CO2 and polymethylhydrosiloxane-a nontoxic, aerobically-stable hydrosilane considered as an industrial waste-via simple inorganic base catalysis. A rare application of the Sabatier principle in organic chemistry led to the discovery of cheap, nontoxic K3PO4 as an efficient catalyst. Preparations of a wide-scope drug-like amines with carbon-isotope label were also successfully achieved, enabling direct use of CO2 in studies of drug absorption, distribution, metabolism and excretion.With the growing urgency of potential catastrophic climate changes due to anthropogenic CO2 emissions,numerous efforts have been devoted to development of synthetic protocols using CO2 as a building block in organic reactions, but the general applicability to complex drug-like substrates remains a challenge.We develop a general protocol for scalable direct N-methylation of a wide-scope drug-like amines using CO2 and polymethylhydrosiloxane—a nontoxic, aerobically-stable hydrosilane considered as an industrial waste—via simple inorganic base catalysis. A rare application of the Sabatier principle in organic chemistry led to the discovery of cheap, nontoxic K3PO4 as an efficient catalyst. Preparations of a wide-scope drug-like amines with carbon-isotope label were also successfully achieved, enabling direct use of CO2 in studies of drug absorption, distribution, metabolism and excretion.

关 键 词：N-METHYLATION Sabatier principle 12CO2/13CO2 Drug-like AMINES INORGANIC base CATALYSIS 

分 类 号：N[自然科学总论]