Synthesis of ortho-haloaminoarenes by aryne insertion of nitrogen-halide bonds.

Journal Article (Journal Article)

A rapid and general access to ortho-haloaminoarenes has been developed by aryne insertion into N-chloramine, N-bromoamine, and N-iodoamine bonds via two complementary protocols harnessing fluoride-promoted 1,2-elimination of ortho-trimethylsilyl aryltriflates. Typically, electron-deficient N-chloramines effectively react with aryne intermediates generated at elevated temperature with CsF, while less stable N-haloamines are found more efficient under milder, TBAF-mediated aryne formation at room temperature. Both protocols demonstrate a good level of regioselectivity and functional group tolerance. Efforts to elucidate the mechanism of N-X insertion are also discussed. The practical value of this transformation is highlighted by rapid synthesis of novel analogues of the antipsychotic cariprazine.

Full Text

Duke Authors

Cited Authors

  • Hendrick, CE; Wang, Q

Published Date

  • January 2015

Published In

Volume / Issue

  • 80 / 2

Start / End Page

  • 1059 - 1069

PubMed ID

  • 25495648

Electronic International Standard Serial Number (EISSN)

  • 1520-6904

International Standard Serial Number (ISSN)

  • 0022-3263

Digital Object Identifier (DOI)

  • 10.1021/jo502541t


  • eng