Synthesis 2016; 48(21): 3730-3742
DOI: 10.1055/s-0035-1562551
paper
© Georg Thieme Verlag Stuttgart · New York

Orthogonal sp3 C1–H and N–H Bond Functionalization of 1,2,3,4-Tetrahydroisoquinolines via the Ugi Four-Component Reaction

Ji-Min Yan
Zhejiang Key Laboratory of Alternative Technologies for Fine Chemicals Process, Shaoxing University, Shaoxing 312000, P. R. of China   Email: chfeng@usx.edu.cn
,
Qi-Fan Bai
Zhejiang Key Laboratory of Alternative Technologies for Fine Chemicals Process, Shaoxing University, Shaoxing 312000, P. R. of China   Email: chfeng@usx.edu.cn
,
Chang Xu
Zhejiang Key Laboratory of Alternative Technologies for Fine Chemicals Process, Shaoxing University, Shaoxing 312000, P. R. of China   Email: chfeng@usx.edu.cn
,
Gaofeng Feng*
Zhejiang Key Laboratory of Alternative Technologies for Fine Chemicals Process, Shaoxing University, Shaoxing 312000, P. R. of China   Email: chfeng@usx.edu.cn
› Author Affiliations
Further Information

Publication History

Received: 20 March 2016

Accepted after revision: 16 May 2016

Publication Date:
14 July 2016 (online)


Ji-Min Yan and Qi-Fan Bai contributed equally to this work.

Abstract

A new protocol for orthogonal sp3 C1–H and N–H bond functionalization of 1,2,3,4-tetrahydroisoquinolines has been established via the Ugi four-component reaction with aldehydes, isonitriles, and carboxylic acids. It was revealed that only the N–H bond could be functionalized when the reaction was performed in acetonitrile at room temperature; however, when the reaction was carried out in toluene at 80 °C, redox-neutral sp3 C1–H bond functionalization of 1,2,3,4-tetrahydroisoquinolines was achieved. Differing from the common role of carboxylic acid as a promoter in redox-neutral amine α-functionalization, the carboxylic acid employed herein is also a reactant. The orthogonal process is compatible with various substrates and provides an appealing­ access to a library of structurally diverse 1,2,3,4-tetrahydro­isoquinolines.

Supporting Information

 
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