Directed Zincation or Magnesiation of 2- and 4-Pyrones and Their Derivatives

Abstract

A regioselective magnesiation of the 2-pyrone scaffold was developed. Magnesiation of this heterocycle by using TMPMgCl·LiCl (TMP = 2,2,6,6-tetramethylpiperidyl) followed by trapping reactions with electrophiles such as aldehydes, allylic bromides, acid chlorides, and aryl iodides provided functionalized 2-pyrones. Furthermore, methyl coumalate and 3,5-dibromo-2H-pyran-2-one were zincated by using TMPZnCl·LiCl to afford zincated heterocycles, which reacted with typical electrophiles. A second magnesiation at position C3 of the 2-pyrone scaffold was achieved by using TMPMgCl·LiCl. Also, the zincation of the 4-pyrone scaffold at position C2 is reported, leading to functionalized 4-pyrones.