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Selective Pd II ‐Catalyzed Acylation of Pyrrole with Aldehydes. Application to the Synthesis of Celastramycin Analogues and Tolmetin
Author(s) -
Santiago Carlos,
Rubio Ibon,
Sotomayor Nuria,
Lete Esther
Publication year - 2020
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.202000444
Subject(s) - chemistry , acylation , pyrrole , pyridine , catalysis , organic chemistry , pyrimidine , aldehyde , medicinal chemistry , combinatorial chemistry , stereochemistry
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.