Synthesis of pentasubstituted 2-aryl pyrroles from boryl and stannyl alkynes: Via one-pot sequential Ti-catalyzed [2 + 2 + 1] pyrrole synthesis/cross coupling reactions

Yukun Cheng, Channing K. Klein, Ian A. Tonks

Research output: Contribution to journalArticlepeer-review

Abstract

Multisubstituted pyrroles are commonly found in many bioactive small molecule scaffolds, yet the synthesis of highly-substituted pyrrole cores remains challenging. Herein, we report an efficient catalytic synthesis of 2-heteroatom-substituted (9-BBN or SnR3) pyrroles via Ti-catalyzed [2 + 2 + 1] heterocoupling of heteroatom-substituted alkynes. In particular, the 9-BBN-alkyne coupling reactions were found to be very sensitive to Lewis basic ligands in the reaction: exchange of pyridine ligands from Ti to B inhibited catalysis, as evidenced by in situ11B NMR studies. The resulting 2-boryl substituted pyrroles can then be used in Suzuki reactions in a one-pot sequential fashion, resulting in pentasubstituted 2-aryl pyrroles that are inaccessible via previous [2 + 2 + 1] heterocoupling strategies. This reaction provides a complementary approach to previous [2 + 2 + 1] heterocouplings of TMS-substituted alkynes, which could be further functionalized via electrophilic aromatic substitution. This journal is

Original languageEnglish (US)
Pages (from-to)10236-10242
Number of pages7
JournalChemical Science
Volume11
Issue number37
DOIs
StatePublished - Oct 7 2020

Bibliographical note

Funding Information:
Financial support was provided by the National Institutes of Health (R35GM119457), and the Alfred P. Sloan Foundation (I. A. T. is a 2017 Sloan Fellow). Instrumentation for the University of Minnesota Chemistry NMR facility was supported from a grant through the National Institutes of Health (S10OD011952). We thank B. J. Foley and Prof. O. V. Ozerov (Texas A&M University) for providing an iridium catalyst used for the synthesis of Bpin-substituted alkynes.

Publisher Copyright:
© The Royal Society of Chemistry.

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