Continuous Flow Magnesiation or Zincation of Acrylonitriles, Acrylates, and Nitroolefins. Application to the Synthesis of Butenolides

Article abstract of DOI:10.1021/acs.orglett.6b00086

Scalable continuous flow procedures are reported for the metalation and downstream functionalization of β-substituted acrylates. The flow conditions allow the metalation of acrylonitriles, acrylates, and nitroolefins at 0.25-2.50 mmol/min conversion rates. Magnesiations can be performed with short residence times (1-20 min) and near-ambient temperature using TMPMgCl·LiCl. Further, high temperature zincation (≤90°C) using TMPZnCl·LiCl is possible. This method allows a simple entry to 2(5H)-furanones by flow generation of magnesiated acrylates and a subsequent reaction with aldehydes. (Chemical Equation Presented).