Palladium-Catalyzed Enantioselective Directed C(sp3)-H Functionalization Using C5-Substituted 8-Aminoquinoline Auxiliaries

Yi Huang; Xiaoyan Lv; Hua-Rong Tong; Wenji He; Ziqian Bai; Hao Wang; Gang He; Gong Chen

doi:10.1021/acs.orglett.3c03688

Palladium-Catalyzed Enantioselective Directed C(sp³)-H Functionalization Using C₅-Substituted 8-Aminoquinoline Auxiliaries

Org Lett. 2024 Jan 12;26(1):94-99. doi: 10.1021/acs.orglett.3c03688. Epub 2023 Dec 27.

Authors

Yi Huang¹, Xiaoyan Lv¹, Hua-Rong Tong¹, Wenji He¹, Ziqian Bai¹, Hao Wang¹, Gang He¹, Gong Chen^{1

2

3}

Affiliations

¹ State Key Laboratory and Institute of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China.
² Frontiers Science Center for New Organic Matter, Nankai University, Tianjin 300071, China.
³ Haihe Laboratory of Sustainable Chemical Transformations, Tianjin 300192, China.

PMID: 38149595
DOI: 10.1021/acs.orglett.3c03688

Abstract

8-Aminoquinoline (AQ) has proven to be a highly effective bidentate directing group for palladium-catalyzed C-H functionalization reactions. However, enantiocontrol of AQ-directed C(sp³)-H functionalization reactions has been challenging. Herein, a new protocol is presented for the Pd-catalyzed enantioselective arylation of unactivated β C(sp³)-H bonds of alkyl carboxamides with aryl iodides using a C₅-iodinated 8-aminoquinolines (IQ) auxiliary in conjugation with a BINOL ligand. Additionally, a C₅-aryl substituted 8-aminoquinoline auxiliary can facilitate enantioselective alkenylation and alkynylation of benzylic C(sp³)-H bonds of 3-arylpropanamides with the corresponding bromide reagents under similar conditions.