Palladium‐Catalyzed Isomerization/(Cyclo)carbonylation of Pentenamides: a Mechanistic Study of the Chemo‐ and Regioselectivity

Abstract

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.

Regioselectivity in Carbonylation of Pentenoic Acid to Synthesize Cyclic Anhydrides

“…Use of the more strongly chelating ligand L5 (as compared to L2 ) in combination with a strong acid also resulted in complete selectivity (>99 %) for 5 a in a yield of 75 % (Table 1, entry 2), while the more bulky and electron‐withdrawing ligand L6 yielded a small amount of 6 a in addition to 5 a in 94 % selectivity (Table 1, entry 3). The use of L6 in combination with acid in catalytic cycloamidocarbonylation of 4‐pentenamide also resulted in high selectivity for the five‐membered imide ring [22] . Remarkably, the ligand L9 , with relatively electron‐withdrawing phenyl groups and a large bite angle, in combination with acid maintained part of its selectivity for 7 a (Table 1, entry 4).…”

“…The use of L6 in combination with acid in catalytic cycloamidocarbonylation of 4-pentenamide also resulted in high selectivity for the five-membered imide ring. [22] Remarkably, the ligand L9, with relatively electron-withdrawing phenyl groups and a large bite angle, in combination with acid maintained part of its selectivity for 7 a (Table 1, entry 4).…”

“…[21] The use of a palladium-based catalytic system for this carbonylation reaction results in intramolecular amidocarbonylation instead of cycloamidomethylation, giving rise to the formation of 2ethylsuccinimide and 2-methylglutarimide, rather than the desired adipimide. [22] These reactions require use of electronwithdrawing phosphine ligands for activation of the poorly nucleophilic amide group. 2-Ethylsuccinic anhydride can be formed with high selectivity from 3-pentenoic acid (3-PEA), using a similar palladium-catalyzed carbonylation reaction.…”

“…Pentenamides – amide derivatives of PEA – have been used as substrates in Rh‐catalyzed intramolecular hydroamidomethylation reactions with the aim to synthesize ϵ‐caprolactam [21] . The use of a palladium‐based catalytic system for this carbonylation reaction results in intramolecular amidocarbonylation instead of cycloamidomethylation, giving rise to the formation of 2‐ethylsuccinimide and 2‐methylglutarimide, rather than the desired adipimide [22] . These reactions require use of electron‐withdrawing phosphine ligands for activation of the poorly nucleophilic amide group.…”

Regiodivergent Carbonylation of Alkenes: Selective Palladium‐Catalyzed Synthesis of Linear and Branched Selenoesters

“…Hence, significant efforts have been devoted to control the l : b ratio by development of specific catalysts/ligands. Indeed, the complementary catalyst systems have been established for hydroformylation, [8] hydrocarboxylation, [3a,d,e] alkoxycarbonylation, [4d–f] aminocarbonylation [5b–i] and thiocarbonylation [7b,c,e] of aromatic olefins, which allow the selective formation of both regiodivergent products. In general, in these processes, the regioselectivity is mainly controlled by changing the type of ligands (mono‐phosphine: branched products, bidentate chelating phosphines: linear products).…”