Regio- and chemoselective metalation of chloropyrimidine derivatives with TMPMgCl x LiCl and TMP(2)Zn x 2 MgCl(2) x 2 LiCl.
Efficient zincation and magnesiation of chlorinated pyrimidines can be performed at convenient temperatures (e.g., 25 and 55 degrees C) by using TMPMgCl x LiCl and TMP(2)Zn x 2 MgCl(2) x 2 LiCl (TMP = 2,2,6,6-tetramethylpiperidyl) as effective bases. Quenching of the resulting zincated or magnesiated pyrimidines with various electrophiles furnishes highly functionalized pyrimidines in 51-93% yield. Oxidative aminations were carried out, thus leading to aminated pyrimidines. By using this methodology, we have also prepared pharmaceutically relevant pyrazolopyrimidines and the fungicide Mepanipyrim.
Mosrin
Marc
M
Ludwig-Maximilians Universität München, Department Chemie & Biochemie, Butenandtstrasse 5-13, Haus F, 81377 München, Germany.
Knochel
Paul
P
D000586:Amination; D002713:Chlorine / Q000737:chemistry; D008094:Lithium / Q000737:chemistry*; D008274:Magnesium / Q000737:chemistry*; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D011720:Pyrazoles / Q000138:chemical synthesis; D011725:Pyridines / Q000138:chemical synthesis; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry; D013696:Temperature; D015032:Zinc / Q000737:chemistry*
D009942:Organometallic Compounds; D011720:Pyrazoles; D011725:Pyridines; D011743:Pyrimidines; C530465:TMPMgCl.LiCl; C118531:pyrazolopyridine; D002713:Chlorine; D008094:Lithium; D008274:Magnesium; D015032:Zinc