Enantio‐ and Regioselective Construction of 1,4‐Diamines via Cascade Hydroamination of Methylene Cyclopropanes

Jian Zhou, Qingjing Yang, Chi Sing Lee*, Jun (Joelle) Wang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

A copper-catalyzed asymmetric hydroamination of methylene cyclopropanes allowed the synthesis of a wide range of chiral 1,4-diamine derivatives in high yields and enantioselectivities (up to 95 % yield and up to >99 % ee). The structure complexity of 1,4-diamines was further increased by using two different functionalized amino agents. Mechanistic studies show a potential pathway involving the hydroamination ring-opening with β-C elimination followed by a cascade hydroamination sequence.
Despite the widespread existence of chiral 1,4-diamines in bioactive molecules and their applications in asymmetric catalysis, the catalytic and asymmetric synthesis of such structures from readily accessible substrates remains a long-standing challenge. Here, we report a Cu-catalyzed asymmetric cascade hydroamination protocol to construct a wide range of chiral 1,4-diamine derivatives in high yields with excellent enatioselectivities (up to 95 % yield and up to >99 % ee). The use of two hydroxylamine esters containing different functionalized amino groups allowed us to increase the complexity of the final 1,4-diamine structures. The desired products could be easily transformed into chiral 1,4-diamines and chiral NH2-Terfenadine. Mechanistic study demonstrates that this reaction proceeds through hydroamination ring-opening and cascade hydroamination sequence.
Original languageEnglish
Article numbere202202160
Number of pages6
JournalAngewandte Chemie. International Edition
Volume61
Issue number24
Early online date25 Mar 2022
DOIs
Publication statusPublished - 13 Jun 2022

Scopus Subject Areas

  • Chemistry(all)
  • Catalysis

User-Defined Keywords

  • Cascade Reactions
  • Copper
  • Diamines
  • Enantioselectivity
  • Hydroamination

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