Premium
Palladium‐Catalyzed Isomerization/(Cyclo)carbonylation of Pentenamides: a Mechanistic Study of the Chemo‐ and Regioselectivity
Author(s) -
Limburg Bart,
Gloaguen Yann,
de Bruijn Hans M.,
Drent Eite,
Bouwman Elisabeth
Publication year - 2017
Publication title -
chemcatchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.497
H-Index - 106
eISSN - 1867-3899
pISSN - 1867-3880
DOI - 10.1002/cctc.201700345
Subject(s) - chemistry , regioselectivity , isomerization , amide , carbonylation , catalysis , alkene , palladium , moiety , medicinal chemistry , intramolecular force , selectivity , imide , organic chemistry , combinatorial chemistry , carbon monoxide
A new isomerizing ring‐closing amidocarbonylation reaction is reported using Pd catalysis with bulky diphosphane ligands. From terminal as well as internal pentenamide isomers (PAs), cyclic imides were obtained in good yield (92 %) with cationic Pd catalysts supported by bis‐PCg ligands (PCg=6‐phospha‐2,4,8‐trioxa‐1,3,5,7‐tetramethyladamant‐6‐yl). An excess of strong acid is required to obtain high selectivity for imide products. From a low‐temperature NMR study it was deduced that N coordination of the amide moiety is responsible for a high selectivity to cyclic imide products. In weakly acidic conditions, O coordination of the amide functionality leads to the formation of cyanoacids (i.e., 5‐cyanovaleric acid, 2‐methyl‐4‐cyanobutyric acid and 2‐ethyl‐3‐cyanopropionic acid). It is proposed that the formation of these cyanoacids occurs through a novel intramolecular tandem dehydrating hydroxycarbonylation reaction of PAs. This reaction also occurs in intermolecular versions of amidocarbonylation with mixtures of alkene and amide substrates. Experiments with N‐alkylated amides have been instrumental in developing mechanistic models. The strong acid co‐catalyst ensures double‐bond isomerization to occur faster than product formation, resulting in the same product mixture, irrespective of the use of terminal or internal pentenamides. The remaining challenge is to arrive at the desired adipimide by overcoming the undesirable regioselectivity caused by chelation of the amide.