Safe Handling of Air-Sensitive Organometallic Reagents Using Schlenk Line Techniques: Negishi Cross-Couplings for Trainee Graduate Students

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A laboratory experiment has been devised to train new graduate trainees in the safe and controlled handling of air-sensitive organometallic reagents using Schlenk lines, high vacuum pumps, liquid nitrogen traps, and cannula transfers. The reaction involves the formation of air-, moisture-, and thermally sensitive 2-pyridyllithium, generated in situ by the reaction of 2-bromopyridine with n-butyllithium in dry THF at −78 °C. Subsequent transmetalation with dried ZnCl2 and reaction with 4-bromo-6-methyl-2-pyrone in the presence of catalytic Pd(PPh3)4 afforded the heterobiaryl product, 4-(2′-pyridyl)-6-methyl-2-pyrone. The many sensitivities of this experiment serve to provide an excellent practical demonstration for new graduate trainees of what can go wrong when experimental procedures are not accurately followed.
Original languageEnglish
Pages (from-to)2656-2660
Number of pages5
Issue number7
Early online date15 Jun 2022
Publication statusPublished - 12 Jul 2022

Bibliographical note

© 2022 The Authors


  • Problem Solving/Decision Making
  • Hands-On Learning/Manipulatives
  • Safety/Hazards
  • Graduate Education/Research Organic Chemistry

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