Dative Directing Group Effects in Ti-Catalyzed [2+2+1] Pyrrole Synthesis: Chemo- and Regioselective Alkyne Heterocoupling

Hsin Chun Chiu, Xin Yi See, Ian A. Tonks

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Transient dative substrate-Ti interactions have been found to play a key role in controlling the regioselectivity of alkyne insertion and [2+2] cycloaddition in Ti-catalyzed [2+2+1] pyrrole synthesis and Ti-catalyzed alkyne hydroamination. TMS-protected alkynes with pendent Lewis basic groups can invert the regioselectivity of TMS-protected alkyne insertion, leading to the selective formation of highly substituted 3-TMS pyrroles. The competency of various potential directing groups was investigated, and it was found that the directing-group effect can be tuned by modifying the catalyst Lewis acidity, the directing-group basicity, or the directing-group tether length. Dative directing-group effects are unexplored with Ti catalysts, and this study demonstrates the potential power of dative substrate-Ti interactions in tuning selectivity.

Original languageEnglish (US)
Pages (from-to)216-223
Number of pages8
JournalACS Catalysis
Volume9
Issue number1
DOIs
StatePublished - Jan 4 2019

Bibliographical note

Funding Information:
Financial support was provided by the National Institutes of Health (1R35GM119457) and the Alfred P. Sloan Foundation (I.A.T. is a 2017 Sloan Fellow). Equipment for the Chemistry Department NMR facility was supported through a grant from the National Institutes of Health (S10OD011952) with matching funds from the University of Minnesota.

Keywords

  • alkynes
  • directing-group effects
  • multicomponent reactions
  • pyrroles
  • titanium

PubMed: MeSH publication types

  • Journal Article

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