Palladium-Catalyzed Enantioselective C(sp3)-H Arylation of 2-Propyl Azaaryls Enabled by an Amino Acid Ligand

Hong Liang Li, Deng Feng Yang, Hua Qing Jing, Jon C. Antilla, Yoichiro Kuninobu

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8 Citations (Scopus)

Abstract

A palladium(II)-catalyzed enantioselective arylation of unbiased secondary C(sp3)-H bonds was developed. The enantioselectivity was controlled by the combination of a pyridyl or isoquinolinyl directing group and an amino acid, N-Boc-2-pentyl proline. A variety of 2-propyl azaaryls and biaryl iodides were employed to provide arylated products in moderate to good yields (up to 82%) with high enantioselectivities (up to 93:7 er). This reaction is a rare example of an amino-acid-enabled enantioselective acyclic methylene C(sp3)-H arylation. Furthermore, the reaction proceeded with high enantioselectivity even on a gram scale, and the product was transformed to a 5,6,7,8-tetrahydroisoquinoline bioactive molecule. Kinetic isotope effect (KIE) experiments indicated that C-H activation is the rate-determining step for the enantioselective C(sp3)-H arylation.

Original languageEnglish
Pages (from-to)1286-1291
Number of pages6
JournalOrganic letters
Volume24
Issue number6
DOIs
Publication statusPublished - Feb 18 2022

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physical and Theoretical Chemistry
  • Organic Chemistry

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