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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 10236-10242 |
| Number of pages | 7 |
| Journal | Chemical Science |
| Volume | 11 |
| Issue number | 37 |
| DOIs | |
| State | Published - 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.