Selective Pd(II)-catalyzed Acylation of Pyrrole with Aldehydes. Application to the Synthesis of Celastramycin analogues and Tolmetin
Ikusi/ Ireki
Data
2020-04-27Egilea
Santiago Alvarez, Carlos
Rubio, Ibon
Sotomayor Anduiza, María Nuria
Lete Expósito, María Esther
European Journal of Organic Chemistry 28 : 4284-4295(2020)
Laburpena
The Pd(II)-catalyzed C-2 acylation of pyrrole with aldehydes in the presence of TBHP as oxidant has been studied for the synthesis of di(hetero)aryl ketones. The use of 2-pyrimidine as directing group leads to 2-acylpyrroles in moderate to good yields, although 2,5-diacylpyrroles are obtained as by products. This side-reaction could be avoided using 3-methy-2-pyridine as directing group, obtaining selectively 2-acylpyrroles. The reaction has been extended to a series of aromatic and heteroaromatic aldehydes, obtaining the best results with electron rich aromatic aldehydes. The methodology has been applied in the synthesis of pyrrolomycin alkaloid Celastramycin analogues and for an improved synthesis of Tolmetin, a nonsteroidal anti-inflammatory drug