Synthesis 2020; 52(08): 1301-1314
DOI: 10.1055/s-0039-1690819
paper
© Georg Thieme Verlag Stuttgart · New York

Metal-Free Halogenation of N-Substituted Enaminoesters and Enaminones: A Facile Access to Functionalized α,α-Dihaloimines

Changfu Qiu
a  College of Pharmaceutical Engineering of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, P. R. of China   Email: lifangyi@tjutcm.edu.cn   Email: lizheng@tjutcm.edu.cn
,
Heshui Yu
a  College of Pharmaceutical Engineering of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, P. R. of China   Email: lifangyi@tjutcm.edu.cn   Email: lizheng@tjutcm.edu.cn
,
Chuanjiang Qiu
b  Chemistry Manufacture Control Department, Accendatech Co., Ltd., Tianjin 300384, P. R. of China
,
Fangyi Li
a  College of Pharmaceutical Engineering of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, P. R. of China   Email: lifangyi@tjutcm.edu.cn   Email: lizheng@tjutcm.edu.cn
,
Tongchuan Suo
a  College of Pharmaceutical Engineering of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, P. R. of China   Email: lifangyi@tjutcm.edu.cn   Email: lizheng@tjutcm.edu.cn
,
Chunhua Wang
a  College of Pharmaceutical Engineering of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, P. R. of China   Email: lifangyi@tjutcm.edu.cn   Email: lizheng@tjutcm.edu.cn
,
Songtao Bie
a  College of Pharmaceutical Engineering of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, P. R. of China   Email: lifangyi@tjutcm.edu.cn   Email: lizheng@tjutcm.edu.cn
,
Zheng Li
a  College of Pharmaceutical Engineering of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, P. R. of China   Email: lifangyi@tjutcm.edu.cn   Email: lizheng@tjutcm.edu.cn
› Author Affiliations
This work is financially supported by the National Major Science and Technology Project of China (No. 2018ZX09201011), the National Natural Science Foundation of China (No. 21604064), and the Science & Technology Development Fund of Tianjin Education Commission for Higher Education (2017KJ138).
Further Information

Publication History

Received: 02 October 2019

Accepted after revision: 20 January 2020

Publication Date:
10 February 2020 (online)


Abstract

An efficient and general method for the synthesis of functionalized α,α-dihaloimines via halogenation of N-substituted enaminoesters and enaminones is described. This reaction, in which both α,α-dihaloimines and mixed α,α-dihaloimines could be achieved in good to excellent yields, is believed to proceed via an α-monohalogenated enamine intermediate. This synthetic method features no use of transition metals, readily accessible substrates, mild reaction conditions, simple and safe operation, and gram scale synthesis. Furthermore, the synthetic utility of the products was demonstrated by their efficient transformations to further useful nitrogen-containing heterocycles and building blocks.

Supporting Information

 
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