Synthesis of Functionalized Tetrahydroquinoline Containing Indole Scaffold via Chemoselective Annulation of Aza- ortho-quinone Methide Precursor

Xiaoke Zhang; Qianlu Xing; Zhengxing Gou; Song Gan; Wenjuan Wang; Ziwei Li; Huawu Shao; Chaoyong Wang

doi:10.1021/acsomega.2c07036

Synthesis of Functionalized Tetrahydroquinoline Containing Indole Scaffold via Chemoselective Annulation of Aza- ortho-quinone Methide Precursor

ACS Omega. 2023 Jun 13;8(25):22352-22360. doi: 10.1021/acsomega.2c07036. eCollection 2023 Jun 27.

Authors

Xiaoke Zhang^{1

2}, Qianlu Xing³, Zhengxing Gou¹, Song Gan², Wenjuan Wang², Ziwei Li¹, Huawu Shao⁴, Chaoyong Wang¹

Affiliations

¹ Central Laboratory, Chongqing University Fuling Hospital, Chongqing 408000, PR China.
² Zunyi Medical University, Zunyi, Guizhou 563000, China.
³ Department of Pediatrics, The Second Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, China.
⁴ Natural Products Research Centre, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, China.

Abstract

The chemoselective annulation of aza-ortho-quinone methide generated by in situ o-chloromethyl sulfonamide has been achieved with bifunctional acyclic olefin. This efficient approach provides access to the diastereoselective synthesis of functionalized tetrahydroquinoline derivatives containing indole scaffolds through the inverse-electron-demand aza-Diels-Alder reaction under mild reaction conditions with excellent results (up to 93% yield, > 20:1 dr). Moreover, this article realized the cyclization of α-halogeno hydrazone with electron-deficient alkene affording the tetrahydropyridazine derivatives, which had never been reported.