Base-Promoted Synthesis of Isoquinolines through a Tandem Reaction of 2-Methyl-arylaldehydes and Nitriles

Sujuan Shuai; Jianyou Mao; Fan Zhou; Qifeng Yan; Lingfeng Chen; Jie Li; Patrick J Walsh; Guang Liang

doi:10.1021/acs.joc.4c00123

Base-Promoted Synthesis of Isoquinolines through a Tandem Reaction of 2-Methyl-arylaldehydes and Nitriles

J Org Chem. 2024 May 17;89(10):6793-6797. doi: 10.1021/acs.joc.4c00123. Epub 2024 May 1.

Authors

Sujuan Shuai^{1

2

3}, Jianyou Mao⁴, Fan Zhou^{1

2

3}, Qifeng Yan^{1

2}, Lingfeng Chen¹, Jie Li^{1

2}, Patrick J Walsh⁵, Guang Liang¹

Affiliations

¹ School of Pharmaceutical Sciences, Hangzhou Medical College, Hangzhou, Zhejiang 311399, China.
² Department of Pharmacy, School of Medicine, Zhejiang University City College, No. 48, Huzhou Road, Hangzhou 310015, P. R. China.
³ College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, P. R. China.
⁴ Institute of Advanced Synthesis, School of Chemistry and Molecular Engineering, Jiangsu National Synergetic Innovation Center for Advanced Materials, Nanjing Tech University, 30 South Puzhu Road, Nanjing 211816, P. R. China.
⁵ Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, Pennsylvania 19104-6323, United States.

PMID: 38691096
DOI: 10.1021/acs.joc.4c00123

Abstract

A convenient method for preparing 3-aryl isoquinolines via a base-promoted tandem reaction is presented. Simply combining commercially available 2-methyl-arylaldehydes, benzonitriles, NaN(SiMe₃)₂, and Cs₂CO₃ enabled the synthesis of a variety of isoquinolines (23 examples, ≤90% yield). Among the syntheses of isoquinolines, the transition metal-free method described here is straightforward, practical, and operationally simple.